Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. As of February 21, total 75,773 confirmed cases worldwide have spread to more than two dozen countries. Transmission of COVID-19 can occur early in the course of infection since SARS-CoV-2 viral loads in asymptomatic patients are similar to that in the symptomatic patients. Therefore, more sensitive diagnostic methods are needed to detect early phase of the infection to prevent secondary or tertiary spreads. Here, we compare the RT-PCR confirmatory test results using two different SARS-CoV-2 viral RNAs from two Korean COVID-19 confirmed cases.RT-PCR method targeting the RdRP gene, which was recommended by WHO guideline, was less sensitive than targeting N genes (as per CDC guideline). Because many countries follow the WHO guideline, our findings may contribute to the early diagnosis of COVID-19.

Towards the investigation and further understanding of the development and propagation of Medicanes, this study explores the forecasting capability of WRF model in case of cyclone “Cleopatra” which affected with extreme rainfall and strong winds Sardinia and Calabria, Italy, in November 2013. This cyclone was unusual in that it developed a warm core but did not fulfill its transformation into a tropical-like cyclone because its core did not expand high enough in the tropospnere. The ERA5 reanalysis dataset was dynamically downscaled from 31 km spatial horizontal resolution to 9 km using WRF model. The methodology consists of; firstly, an extensive physical parameterization schemes sensitivity test and consequently, a short-range ensemble forecasting implementation based on the highest statistical scored physics configuration. All simulation results were validated against surface observations and remote sensing products. Subsequently, the modeled cyclone trajectories are compared to satellite imagery derived from EUMETSAT-SEVIRI gridded data. The findings of the conducted analysis illustrate that ensemble average displays significant difference in performance compared to any of the deterministic runs individually, suggesting that ensemble forecasts will be beneficial in studies assessing cyclonic events in the Mediterranean region.

Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Sensory Processing Sensitivity (SPS) is a trait describing inter-individual differences in sensitivity to environments, both positive and negative ones. SPS has attracted growing societal interest. However, (neuro)scientific evidence is lagging behind. We critically discuss how to measure SPS, how it relates to other theories of Environmental Sensitivity and other temperament and personality traits, how SPS interacts with environments to influence (a)typical development, what the underlying aetiologies and mechanisms are, and its relation to mental disorders involving sensory sensitivities. Drawing on the diverse expertise of the authors, we set an agenda for future research to stimulate the field. We conclude that SPS is a heritable, evolutionarily conserved trait, linked to increased risk for psychopathology and stress-related problems in response to negative environments, as well as to greater benefits (e.g., intervention responsivity, positive mood) in positive environments. We need advances in objective assessment of SPS, understanding mechanisms, differentiating it from (seemingly) related mental disorders, to exploit the potential of SPS to improve mental health, preserve human capital, and prevent adverse effects.

The COVID-19 pandemic has created huge damage to society and brought panics around the world. Such panics can be ascribed to the seemingly deceptive features of the COVID-19: compared to other deadly viral outspreads, it has medium transmission and mortality rates. As a result, the severity of the causative coronavirus, SARS-CoV-2, was deeply underestimated by the society at the beginning of the COVID-19 outbreak. Based on this, in this review, we define the viruses with features similar to those of SARS-CoV-2 as the Panic Zone viruses. To contain those viruses, accurate and fast diagnosis followed by effective isolation and treatment of patients are pivotal at the early stage of virus breakouts. This is especially true when there is no cure or vaccine available for a transmissible disease, which is the case for current COVID-19 pandemic. As of January 2021, more than two hundred kits for the COVID-19 diagnosis on the market are surveyed in this review, while emerging sensing techniques for SARS-CoV-2 are also discussed. It is of critical importance to rationally use these kits for the efficient management and control of the Panic Zone viruses. Therefore, we discuss guidelines to select diagnostic kits at different outbreak stages of the Panic Zone viruses, SARS-CoV-2 in particular. While it is of utmost importance to use nucleic acid-based detection kits with low false negativity (high sensitivity) at the early stage of an outbreak, the low false positivity (high specificity) gains its importance at later stages of the outbreak. When a society is set to reopen from the lock-down stage of the COVID-19 pandemic, it becomes critical to have antibody based immunoassay kits with high specificity to identify people who can safely return to the society after their recovery of SARS-CoV-2 infections. Given that the emergence of mutant viruses at the beginning of 2021 has complicated current battle against the COVID-19, we also discussed approaches and guidelines to detect viral mutants in the middle of the second wave of the pandemic that started at the end of 2020. Finally, since a massive attack from a viral pandemic requires a massive defense from the whole society, we urge both government and private sectors to research and develop more affordable and reliable point-of-care testing (POCT) kits, which can be used massively by the general public (and therefore called as massive POCT) to contain Panic Zone viruses in future.

That how to improve the sensitivity and the detection ability of the Large-caliber sensor is critical to satisfy the requirement of heavy vehicle wear condition monitoring. In this paper, we introduced the LC resonance principle to the design of sensor with large flow channel (7mm). The resonant exciting coil increases the impedance change of the exciting circuit caused by wear particles which magnify the current difference between the two exciting coils and improve the sensitivity of the sensor. The resonant induction coil greatly suppresses the interference signals and magnifies the weak induced electromotive force which is beneficial to enhance the detection ability. In order to boost the detectability for different materials particles, a phase controlled variable-frequency exciting system (PCVFES) was adopted to automatically switch the exciting frequency between 284kHz for ferromagnetic particles and 420KHz for non-ferromagnetic particles. For the weak signal detection, based on the essential characteristic of the signal, we apply a simpler method that modified lock-in amplifier (MLIA) rather than the conventional algorithms (Wavelet transform, EMD). Results show that using these methods the sensitivity and the detection ability of the sensor are significantly improved and the 75μm iron particles and 220μm copper particles were successfully detected which realizes the initial abnormal wear monitoring for the large flow project.

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

The present novel corona virus (2019-nCoV) infection has created a global emergency situation by spreading all over the world in a large scale within very short time period. The infection induced death rate is also very high. There is no vaccine or anti-viral medicine for such infection. So at this moment a major worldwide problem is that how we can control this pandemic. On the other hand, India is a high population density country, where the corona virus disease (COVID-19) has started to spread from $1^{st}$ week of March, 2020 in a significant number of COVID-19 positive cases. Due to this high population density human to human social contact rate is very high in India. So control of the pandemic COVID-19 in early stage is very urgent and challenging problem. Mathematical models are employed in this paper to study the COVID-19 dynamics, to identify the influential parameters and to find the proper prevention strategies to reduce the outbreak size. In this work, we have formulated a deterministic compartmental model to study the spreading of COVID-19 and estimated the model parameters by fitting the model with reported data of ongoing pandemic in India. Sensitivity analysis has been done to identify the key model parameters. The basic reproduction number has been estimated from actual data and the effective basic reproduction number has been studied on the basis of reported cases. Some effective preventive measures and their impacts on the disease dynamics have also been studied. Future trends of the disease transmission has been Predicted from our model with some control measures. Finally, the positive measures to control the disease have been summarized.

Highly flexible manufacturing systems require continuous run-time (self-) optimization of processes with respect to various parameters, e.g. efficiency, availability, energy consumption etc. A promising approach for achieving (self-) optimization in manufacturing systems is the usage of the context sensitivity approach. Thereby the Cyber-Physical Systems play an important role as sources of information to achieve context sensitivity. In this paper it is demonstrated how context sensitivity can be used to realize a holistic solution for (self-) optimization of discrete flexible manufacturing systems, by making use of Cyber-Physical System integrated in manufacturing systems/processes. A generic approach for context sensitivity, based on self-learning algorithms, is proposed aiming at a various manufacturing systems. The new solution is propos encompassing run-time context extractor and optimizer. Based on the self-learning module both context extraction and optimizer are continuously learning and improving their performance. The solution is following Service Oriented Architecture principles. The generic solution is developed and then applied to two very different manufacturing processes. This paper proposes a holistic solution to achieve context sensitivity for Flexible Manufacturing Systems, whereby the knowledge created by applying the context sensitivity approach can be used for (self-) optimization of manufacturing processes.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

In this paper, a solenoid based linearly movable armature system is designed using robust control theory in order to improve the performance of the system. Reference track method is the best performance analysis for position control systems. Among the robust controllers, H infinity mixed-sensitivity and Mixed H 2 /H∞ with Regional Pole Placement Controllers are used to improve the performance of the system. Comparison of the proposed controllers for tracking a reference displacement signals (step and sine wave) and a promising simulation result have been obtained.

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

In this work, we report synthesis of Cu, Pt and Pd doped SnO₂ powders and their comparative CO gas sensing studies. Dopants were incorporated into SnO₂ nanostructures using chemical and impregnation methods by using urea and ammonia as precipitation agents. The synthesized samples were characterized using X-ray diffraction (XRD), Raman spectroscopy, Scanning electron microscopy (SEM) and High resolution transmission electron microscopy (HR-TEM). The presence of dopants within the SnO₂ nanostructures was evidenced from HR-TEM. Doped powders utilizing chemical methods with urea as precipitation agent presented higher sensitivities compared to the remaining, which is due to the formation of uniform and homogeneous particles resulted from the temperature assisted synthesis. The particle sizes of doped SnO₂ nanostructures were in the range of 40-100 nm. An enhanced sensitivity around 1783 was achieved with Cu doped SnO₂ when compared with two other dopants i.e., Pt (1200) and Pd: SnO₂(502). The high sensitivity of Cu: SnO₂ is due to formation of CuO and its excellent association and dissociation in the presence of CO with adsorbed atmospheric oxygen at sensor operation temperatures resulted in high conductance. Cu: SnO₂ may be an alternative and cost effective sensor for industrial applications.

Global population is predicted to approach 10 billion by 2050, an increase of over 2 billion from today. To meet the demands of growing, geographically and socio-economically diversified nations, we need to diversity and expand agricultural production. This expansion of agricultural productivity will need to occur under increasing biotic, and environmental constraints driven by climate change. Clustered regularly interspaced short palindromic repeats-site directed nucleases (CRISPR-SDN) and similar genome editing technologies will likely be key enablers to meet future agricultural needs. While the application of CRISPR-Cas9 mediated genome editing has led the way, the use of CRISPR-Cas12a is also increasing significantly for genome engineering of plants. The popularity of the CRISPR-Cas12a, the type V (class-II) system, is gaining momentum because of its versatility and simplified features. These include the use of a small guide RNA devoid of trans-activating crispr RNA (tracrRNA), targeting of T-rich regions of the genome where Cas9 is not suitable for use, RNA processing capability facilitating simpler multiplexing, and its ability to generate double strand breaks (DSB) with staggered ends. Many monocot and dicot species have been successfully edited using this Cas12a system and further research is ongoing to improve its efficiency in plants, including improving the temperature stability of the Cas12a enzyme, identifying new variants of Cas12a or synthetically producing Cas12a with flexible PAM sequences. In this review we provide a comparative survey of CRISPR-Cas12a and Cas9, and provide a perspective on applications of CRISPR-Cas12 in agriculture.

Recently, light traps using light-emitting diode (LED) lights have been applied to monitor or control insect pests. The oriental armyworm, Mythimna separata Walker, is an important insect pest that has caused damage to several cereal crops, including corn, wheat and rice. The present study aims to seek out a sensitive wavelength causing high phototactic response in M. separata. The study evaluated the phototactic responses of M. separata moths to several LED lights of different wavelengths and luminance intensities under laboratory condition. Results showed that green (520 nm) LED light resulted in significant phototactic response of M. separata moths compared to LED lights of other wavelengths. Additionally, the highest attraction rate of the moths to green LED light appeared in luminance intensity group of 200 lux compared to the other intensities groups. Experiments under optimum conditions based on the above experiments revealed that the green LED light exhibited the strongest attraction rate (64.44%) among all experimental groups. An experiment performed in a net cage also showed that green LED light resulted in the highest phototactic response of M. separata moths, 1.7 times more than a commercial black light used as control. These findings clearly demonstrate that M. separata moths have a high sensitivity to the green LED light. Therefore, a light trap equipped with green LED light could be useful for monitoring and controlling M. separata moths.

This paper presents a methodology for determining the sensitivity of the main air flow directions in ventilation subnetworks to changes of aerodynamic resistance and of air density in mine workings. Formulae for determination of the sensitivity of the main subnetwork air flows by establishing the degree of dependency of the air volume stream in a given working on the variations in resistance or air density of other workings of the network have been developed. They have been implemented in the VentGraph mine ventilation network simulator. This software, widely used in Polish collieries provides an extended possibility to predict the process of ventilation, air distribution and, in the case of underground fire, also the spread of combustion gasses. The new method facilitates assessment by mine ventilation services of the stability of ventilation systems in exploitation areas and determine of the sensitivity of the main subnetwork air flow directions to changes of aerodynamic resistance and air density. Recently in some Polish collieries new longwalls are developed in seams located deeper then the bottom of the intake shaft. Such solution is called “exploitation below the level of access” or “sublevel”. The new approach may be applied to such developments to assess the potential of changes of direction and air flow rates. In addition, interpretation of the developed sensitivity indicator is presented. While analyzing air distributions for sublevel exploitation, application of current numerical models for calculations of the distribution results in tangible benefits, such as the evaluation of the safety or risk levels for such exploitation. Application of the VentGraph computer program, and particularly the module POŻAR (fire) with the newly developed options, enables an additional approach to the sensitivity indicator in evaluating air flow safety levels for the risks present during exploitation below the level of the intake shaft. The analyses performed and examples presented enabled useful conclusions in mining practice to be drawn.

Analysis of 49 strains of F. langsethiae originating from northern Europe (Russia, Finland, Sweden, UK, Norway, and Latvia) revealed the presence of spontaneous auxotrophic mutants that reflect natural intraspecific diversity. Our investigations detected that 49.0% of F. langsethiae strains were auxotrophic mutants for biotin, and 8.2% of the strains required thiamine as a growth factor. They failed to grow on vitamin-free media. For both prototrophic and auxotrophic strains, no growth defect was observed in rich organic media. Without essential vitamins, a significant reduction in the growth of the auxotrophic strains results in a decrease of the formation of T-2 toxin and diacetoxyscirpenol. In addition, all analysed F. langsethiae strains were distinguished into two subgroups based on PCR product sizes. According to our results, 26 and 23 strains of F. langsethiae belong to subgroups I and II respectively. We determined that the deletion in the IGS region of the rDNA of F. langsethiae belonging to subgroup II is linked with temperature sensitivity and causes a decrease in strain growth at 30 °C. Four thiamine auxotrophic strains were found in subgroup I, while 21 biotin auxotrophic strains were detected in subgroups II. To the best of our knowledge, the spontaneous mutations in F. langsethiae observed in the present work have not been previously reported.

In the promptness of the COVID-19 outbreak, it would be very important to observe and estimate the pattern of diseases to reduce the contagious infection. To study this effect, we developed a COVID-19 analytical epidemic framework that combines with isolation and lockdown effect by incorporating five various groups of individuals. Then we analyze the model by evaluating the equilibrium points and analyzing their stability as well as determining the basic reproduction number. The extensive numerical simulations show the dynamics of a different group of the population over time. Thus, our findings based on the sensitivity analysis and the reproduction number highlight the role of outbreak of the virus that can be useful to avoid a massive collapse in Bangladesh and rest of the world. The outcome of this study concludes that outbreak will be in control which ensures the social and economic stability.

The value of QuantiFERON in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 128 cases with active PTB and 128 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. Their IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; P < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

As fossil-fueled heating in the building sector is responsible for 16 % of Germanys total CO2 emissions, it is of great importance to use climate-neutral alternatives for the decarbonization of this sector. Options for the climate-neutral heating of buildings include electricity or hydrogen as energy carriers, both explicitly considered by German policy. In this paper, bottom-up studies are conducted to investigate the role of hydrogen for the climate-neutral energy supply of ten selected residential buildings in comparison to electricity-based systems. Based on a selection of as different typical buildings as possible for single- (SFH) and multi-family houses (MFH) of different construction years, demand profiles are simulated for each building and the respective cost-optimal supply system is determined. For the construction of this system, the electricity-based technologies available are electric heater and heat pump as well as the hydrogen-based technologies hydrogen boiler and fuel cell combined heat and power (CHP) system. Based on the results of the optimization, sensitivity analyses are performed. These analyses aim to identify threshold values of the hydrogen price for the use of hydrogen in building energy systems as well as to make the quantities of hydrogen consumed visible.The identified threshold values show the significant role of hydrogen-operated CHP in MFH if the hydrogen price reaches 0.17 €/kWh_H2 in 2050 at an electricity price of 0.31 €/kWh_el. So, hydrogen-based energy systems represent an economically viable alternative to electricity-based systems with heat pumps. We identify electricity to hydrogen price ratios for the economically viable use of hydrogen in the examined buildings that range from 1.67 to 2.82. According to these ratios, the economically reasonable use of hydrogen in buildings can be derived. For the individual building groups for the year 2050, a ratio of 2.5 can be determined for SFH and 1.8 for MFH, that is favored by the use of CHP which also supplies electricity to the buildings. However, the role hydrogen will finally play in German residential buildings in the future depends to a large extent on political decisions on distribution issues and price signals.

There is a potential for synergy effects in utilizing CO2 for both enhanced gas recovery (EGR) and geothermal energy extraction (CO2-plume geothermal, CPG) from natural gas reservoirs. This “combined CO2-EGR–CPG system” has been introduced as a feasible approach that constitutes a CO2 Capture double-Utilization and Storage (CCUUS) system. In this study, we carry out reservoir simulations, using TOUGH2, to evaluate the sensitivity of the natural gas recovery, pressure buildup, and geothermal power generation performance of the combined system to various key reservoir and operational parameters. The reservoir parameters include horizontal permeability, permeability anisotropy, reservoir temperature, and pore-size-distribution index; while the operational parameters include wellbore diameter and ambient surface temperature. Using an example of a natural gas reservoir model, we also investigate the effects of different strategies of transitioning from the CO2-EGR stage to the CPG stage on the energy-recovery performance metrics and on the two-phase fluid-flow regime in the production well. The simulation results show that overlapping the CO2-EGR and CPG stages and having a relatively brief period of CO2 injection but no production (which we call the CO2-plume establishment stage) achieves the best overall energy (natural gas and geothermal) recovery performance. Permeability anisotropy and reservoir temperature are the parameters the natural gas recovery performance of the combined system is most sensitive to. The geothermal power generation performance is most sensitive to the reservoir temperature and the production wellbore diameter. The results of this study pave the way for future CPG-based geothermal power-generation optimization studies. For a CO2-EGR–CPG project, the results can be a guide regarding the required accuracy of the reservoir parameters during exploration and data acquisition.

1) Background: Respiratory tract infections (RTI) has been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district; 2) Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI); 3) Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being streptococcus pneumonia 43.3% (n = 342), followed by pseudomonas aeruginosa 22.8% (n = 180), staphylococcus aurous 13.8% (n = 109), Escherichia Coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic; and 4) Conclusions: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.

WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stem- ness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2^nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1, we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2^nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline’s efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (ra- dial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3^rd order biological hypotheses emerge some of which are con- firmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest.

Based on the geologic conditions of natural gas hydrate (NGH) accumulations in the Shenhu area, northern slope of the South China Sea, this paper used a method of combining reservoir stimulation technique (RST) with depressurization to investigate the conversion efficiency of marine NGH reservoirs in different intrinsic permeability and initial NGH saturation conditions, and analyze the influence of variably-stimulation effect on marine NGH conversion efficiency in different accumulation conditions, provided a reference scheme for improving the NGH conversion efficiency in the Shenhu area. In this work, we performed calculations for the variations in CH4 production rate and cumulative volume of CH4 in different initial NGH saturation, intrinsic permeability and stimulation effect conditions, variance analysis and range analysis methods were used to analyze the significance of these key factors and their interaction, and investigated the sensitivity of stimulation effect on NGH conversion efficiency, respectively. The simulation results showed that stimulation effect have a significant influence on NGH conversion efficiency, and the influence of interaction between these three factors were not obvious. Possibly most important, we clarified an optimum stimulation effect for higher NGH conversion efficiency under different accumulation conditions, especially in low-permeability and high-saturation, which corresponding stimulation effect were different.

The availability of new self-sensing cement-based strain sensors allows the development of dense sensor networks for Structural Health Monitoring (SHM) of reinforced concrete structures. These sensors are fabricated by doping cement-matrix materials with conductive fillers, such as Multi Walled Carbon Nanotubes (MWCNTs), and can be embedded into structural elements made of reinforced concrete prior to casting. The strain sensing principle is based on the multifunctional composites outputting a measurable change in their electrical properties when subjected to a deformation. Previous work by the authors was devoted to material fabrication, modeling and applications in SHM. In this paper, we investigate the behavior of several sensors fabricated with and without aggregates and with different MWCNTs content. The strain sensitivity of the sensors, in terms of fractional change in electrical resistivity for unit strain, as well as their linearity are investigated through experimental testing under both static and dynamically varying compressive loadings. Moreover, the responses of the sensors when subjected to destructive compressive tests are evaluated. Overall, the presented results contribute to improving the scientific knowledge on the behavior of smart concrete sensors and to furthering their understanding for SHM applications.

Since the beginning of the year 2020, the global healthcare system has been challenged by the threat of the SARS-COV 2 virus. Molecular, antigen, and antibody testing are the mainstay to identify infected patients and fight the virus. Molecular and antigen tests that detect the presence of the virus are relevant in the acute phase only. Serological assays detect antibodies to the Sars-CoV-2 virus in the recovering and recovered phase. Each testing methodology has its advantages and disadvantages. To evaluate the test methods, sensitivity (percent positive agreement - PPA) and specificity (percent negative agreement – PNA) are the most common metrics utilized, followed by the positive and negative predictive value (PPV and NPV), the probability that a positive or negative test result represents a true positive or negative patient. In this paper, we illustrate how patient risk and clinical costs are driven by false-positive and false-negative results. We demonstrate the value of reporting PFP (probability of false positive results), PFN (probability of false negative results), and costs to patients and healthcare. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by one positive SARS COV-2).

Previous research has shown that the effectiveness of selecting filter set from a large set of commercial broadband filters by vector analyzing method based on maximum linear independence (MLI). However, the traditional MLI is suboptimal due to predefining the first filter of the selected filter set being the maximum ℓ2 norm among all those of the filters. An exhaustive imaging simulation is conducted to investigate the features of the most competent filter set. In the simulation, every filter in a subset of all the filters is selected serving as the first filter in turn. From the results of the simulation, we found there are remarkable characteristics for the most competent filter set. Besides smaller condition number, the geometric features of the best-performed filter set comprise the distinct peak of the transmittance of the first filter, the generally uniform distributing of the peaks of the transmittance curve of the filters, the substantial overlapping of the transmittance curves with those of the adjacent filer sets. Therefore, the best-performed filter sets can be decided intuitively by simple vector analyzing and just a few experimental verifications. This work would be useful for optimizing spectral sensitivity of broadband multispectral imaging sensors or SFA sensors.

Is it true that the nuclear technology applied to electric energy generation offers a clean, safe, reliable and affordable i.e. sustainable alternative? Yes it is, but its impact on the environment strongly depends on the implementation bearing residual risks due to a human factor, technical failures or natural catastrophes. A full response is therefore difficult and can first be given when the wicked multi-disciplinary problems get well formulated and “solved”. These problems have multi-dimensional nature lying at the interface between: necessary R&D effort, the industrial deployment and the technology impact in view of the environmental sustainability including the management of produced hazardous waste. This enormous complexity indicates that just a description of the problem might represent a problem. The paper proposes a holistic approach to assess the nuclear energy systems potential with respect to sustainable performance applying Multi-criteria decision analysis with a suitable objective tree and a multi-level criteria structure and examines the trading-off techniques for ranking of the alternatives. The framework proposes a multi-criteria and multi-stakeholders treatment which can be used as a pre-decisional support towards an implementation of nuclear fuel cycles adapted to national preferences and priorities. Proposed approach addresses some aspects of the environmental footprint of nuclear energy systems. Advanced nuclear fuel cycles, previously investigated by the NEA/OECD expert group WASTEMAN, are analyzed as a case study. Sustainability facets of waste management, resource utilization and economics are in focus.

DNA repair helps in maintaining the proper and healthy functioning for the cells in the human body. Failure in DNA repair process can lead to aberrations as well as tumorous stages. There are various types of damages that a DNA can go through, one of which is the DNA double strand breaks (DSB) that can be repaired via homologous recombination (HR). RAD51 plays a central role in HR and has been implicated as a negative/poor prognostic marker for colorectal adenocarcinoma, with high expression in colorectal cancer. Mechanistically, RAD51AP1 facilitates RAD51 during the repairing process by binding with RAD51 via two DNA binding sites, thus helping in the D-loop formation in the HR process. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, RAD51AP1-XRCC2 is one such 2^nd order combination whose relation needs to be tested under the influence recently developed Porcupine-WNT inhibitor ETC-1922159. The x-ray repair cross complementing XRCC family is known to work as a mediator or stabilizer for RAD51 during the HR process. The inhibitor is known to suppress Porcupine and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2^nd order level after the drug was administered. The in silico observations showed that the combination of RAD51AP1-XRCC2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both RAD51AP1 and XRCC2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3^rd order combinations of RAD51-X-X & RAD51AP1-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hibert Schmidth Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested RAD51/RAD51AP1 related 3^rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

Promoter is a small region of DNA sequence in response to various transcription factors, which initiates a particular gene expression. The promoter-engineered bio-sensor can activate or repress gene expression through transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids or redox molecule, however, the reported applications of promoter enhanced bio-sensor are not too much. This review paper highlights the strategies of construction of promoter-gene engineered bio-sensor with human and bacteria’s genetic promoter array for high-throughput screening (HTS) molecular drugs, study of membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factor, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These bio-sensors’s sensitivity and specificity can be further improved by proposed approaches of Mn²⁺ and Mg²⁺ added random Error-prone PCR and site-directed mutagenesis which is applied for construction of bacteria’s “mutant library”. It is expected to establish flexible HTS platform (Bio-sensor array) to large-scale screen transcription factor-acting drugs, reducing the toxicity of intermediate compounds, and constructing gene dynamic regulatory system in “push and pull” mode to effectively regulate the valuable medicinal product production. This proposed novel promoter-engineered biosensors aided synthetic genetic circuit construction will maximize the efficiency of bio-synthesis of medicinal compound, which will greatly promote the development of microbial metabolic engineering and biomedical science.

Digital Elevation Models (DEMs) are essential in watershed delineation, but the sensitivity of simulated runoff to DEM resolution is poorly understood. This study investigates the impact of DEM resolution on topological attributes and simulated runoff in the Mahabad Dam watershed, Iran. To delineate the watershed, DEMs with 12.5 m, 30 m, and 90 m resolutions were acquired from the ALOS PALSAR, Space Shuttle Radar Topography Mission (SRTM), and ASTER global DEM data source, respectively. Watershed and streamlines were delineated in ArcGIS, with hydrologic analyses performed using the Soil and Water Assessment Tool (SWAT). Sensitivity analysis on parameters contributing to runoff was done using Sequential Uncertainties Fitting Ver-2 (SUFI-2) Algorithm, in SWAT Calibration and Uncertainty Procedures (SWAT-CUP) software. Results showed the watershed area, reach lengths, and elevations in the watershed varied due to DEM resolutions. Higher amounts of runoff were generated when DEMs with finer resolutions were implemented. The 12.5 m DEM generated 3.48% and 0.42% more runoff compared with 90 m and 30 m DEMs, respectively. SWAT-CUP results showed the sensitivity of parameters contributing to runoff changes under different DEM resolutions. Regardless of DEM resolution, surface properties, available water capacity, and moisture levels in the soil are the most sensitive parameters. As the distribution of slope changes in different DEM resolutions, surface parameters are most affected. The findings indicate to reduce computation time and speed up computation procedures, researchers may use DEMs with coarser resolutions at the expense of minor decreases in accuracy.

Evidence shows that weightloss improves insulin sensitivity but few studies have examined the effect of macronutrient composition independently of weight loss on direct measures of insulin sensitivity. We randomised 89 overweight or obese women to either a standard diet (StdD) that was intended to be low in fat and relatively high in carbohydrate (n=42) or to a relatively high protein (up to 30% of energy), relatively high fibre (>30g/day) diet (HPHFib) (n=47) for 10 weeks. Advice regarding strict adherence to energy intake goals was not given. Insulin sensitivity and secretion was assessed by a novel method - the Dynamic Insulin Sensitivity and Secretion Test (DISST). Although there were significant improvements in body composition and most cardiometabolic risk factors on HPHFib, insulin sensitivity was reduced by 19.3% (95% CI: 31.8, 4.5%; p=0.013) in comparison with StdD. We conclude that the reduction in insulin sensitivity after a diet relatively high in both protein and fibre, despite cardiometabolic improvements, suggests insulin sensitivity may reflect metabolic adaptations to dietary composition for maintenance of glucose homeostasis, rather than impaired metabolism.

Shale gas reservoirs (SGR) are important replacements for conventional energy resources and have been widely exploited by hydraulic fracturing technologies. On the one hand, due to the inherent ultra-low permeability and porosity, there is stress sensitivity in the reservoirs generally. On the other hand, hydraulic fractures and the stimulated reservoir volume (SRV) generated by the massive hydraulic fracturing operation have contrast properties with the original reservoirs. These two phenomena bring huge challenges in SGR transient pressure analysis. Although some works in the literatures have been done on the transient pressure analysis of multi-fractured horizontal wells in SGR, unfortunately, none of them has taken the stress sensitivity and spatially varying permeability of SRV zone into consideration simultaneously. To fill this gap, this paper first idealizes the SGR to be four linear composite regions. What’s more, SRV zone is further divided into sub-sections on the basis of non-uniform distribution of proppant within SRV zone which easily yields spatially varying permeability away from the main hydraulic fracture. The stress sensitivity is characterized by the varying permeability depended on the pore pressure. By means of perturbation transformation and Laplace transformation, an analytical multi-linear flow model (MLFM) is obtained and validated by the comparison with the previous model. On the basis of our model, the flow regimes are identified and the sensitivity analysis of critical parameters are conducted to further understand the transient pressure behaviors. The research results provided by this work are of significance for well test interpretation and production performance analysis of SGR.

\textsc{Background} Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. Currently, a major problem in biology is to cherry pick the combinations based on expert advice, literature survey or guesses for investigation. The search and wet lab testing of these combinations costs a lot in terms of time, investment and energy. In a recent development of the PORCN-WNT inhibitor ETC-1922159 for colorectal cancer, a list of down-regulated genes were recorded in a time buffer after the administration of the drug. The regulation of the genes were recorded individually but for a majority, it is still not known which higher ($\geq 2$) order combinations might be playing a greater role in the pathway. \textsc{Results} The pipeline provides a prioritised list of important $2^{nd}$ order combinations of a range of family of genes involved in the Wnt pathway. More specifically, it reveals the various unexplored FZD-WNT combinations that have been untested till now in the pathway. In relation to ETC-1922159 affected combinations, the down-regulation of LGR-RNF family after the drug treatment is evident in these rankings as it takes bottom priorities for LGR5-RNF43 combination. The LGR6-RNF43 takes higher ranking than LGR5-RNF43, indicating that it might not be playing a greater role as LGR5 during the Wnt enhancing signals. These rankings confirm the efficacy of the proposed search engine design. \textsc{Conclusion} A pipeline has been developed to prioritise an $n^{th}$ order combination of factors that affect a signaling pathway. It takes into account the sensitivity indices computed from variance based (SOBOL) and density-kernel based (HSIC) methods to estimate the influence of each factor or combination of factors. These are then fed as feature vectors into a powerful support vector ranking algorithm that produces a ranked list of the interactions/combinations.

Multiphase systems are important in minerals processing, and usually include solid-solid and solid-fluid systems. Examples of operations in multiphase systems include flotation, dewatering, and magnetic separation, among several other unit operations. In this paper, the current trends in the process system engineering tasks of modeling, design, and optimization, in multiphase systems, are analyzed. Different scales of size and time are included, and therefore the analysis includes modeling at the molecular level and unit operation level, and the application of optimization for the design of a plant. New strategies for the modeling and optimization of multiphase systems are also included, with a strong focus on the application of artificial intelligence (AI) and the combination of experimentation and modeling with response surface methodology (RSM). The paper finishes with tools to study the uncertainty, both epistemic and stochastic, which is present in all mineral processing operations. It is shown that all these areas are very active and can help to understand, operate, design, and optimize mineral processing that involves multiphase systems.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

Typhoon Durian forming over the Western North Pacific Ocean and entering into the South China Sea (SCS), caused extreme and widespread damages in 2006. In this research, sensitivity analyses on different physical parameterization schemes of the Weather Research and Forecasting Atmospheric Model (WRF-ATM) have been utilized to study typhoon Durian. Model accuracy and performance testing were investigated with different initial conditions during the tropical cyclone simulation in the SCS. The initial and boundary conditions (IBCs) for all experiments were derived from the European Centre for Medium Range Weather Forecasts (ECMWF), Re-Analysis Interim (ERAI), and the National Centers for Environmental Prediction (NCEP) with Final (FNL) analysis data compiled through the WRF-ATM model. The sensitivity analysis results indicated a major improvement for the cumulus scheme by using the Grell-Devenyi scheme along with the PBL scheme of Yonsei University, mixed-phase microphysics scheme of the WRF Single Moment 5-class and IBCs for ECMWF-ERAI of TC simulation under the context of Wind-Pressure Relationships. This predicted better track and intensity comparing with these of the Joint Typhoon Warning Center. The results revealed that the TC track and intensity were well simulated by the WSM5-GD combination for the WRF-ATM model with an intensity error of 1.69 hPa for minimum surface level pressure, maximum wind speed of 1.83 knots and average track error of 25 km in 72 hours. The simulations showed that the potential track and intensity error decreased with the delayed IBCs, suggesting that the model simulation is more dependable when the coast is approached by the TC.

An essential step in solving any topology optimization problem is determining the sensitivities of the objective function and optimization constraints. Unfortunately, these sensitivities are usually derived and implemented manually. Nontrivial objective functions and constraints, especially with the involvement of material and geometric nonlinearities, need strenuous mathematical derivation, leading to error-prone implementation. Another intriguing approach to finding sensitivities is automatic differentiation. This paper uses the automatic differentiation and adjoint method to find the sensitivities for two multiphysics topology optimization problems: 1) thermoelasticity and 2) piezoelectricity. This approach is not limited to these examples and can be easily extended to other single- or multi-physics topology optimization problems.

Aim: This research is aimed at examining the cost-effectiveness of olanzapine versus risperidone in dementia patients with behavioural and psychological symptoms in Thailand. Methods: An existing Markov model based on a critical review through the comprehensive literature search and a justification for the most appropriate model for a Thai setting was adapted to simulate the disease progression of patients with dementia with behavioural disturbances until their need for full-time care (FTC). The time to the FTC state was estimated by a predictive equation developed by Rive et al. (2010). The model was conducted to assess the expected costs and outcomes associated with olanzapine compared with risperidone for Thai patients with BPSD aged 60 years and above. This model performed over a five-year time horizon with a one-month cycle length based on a societal perspective. The incremental cost-effectiveness ratio was used as the estimated outcome. Sensitivity analyses were also conducted to demonstrate the robustness of the results. Results: Over 5 years, olanzapine was found to be a cost-effective therapeutic option for the treatment of behaviourally disturbed patients with dementia compared with risperidone, in Thailand from a societal perspective (ICER < THB 160,000). The model underwent extensive sensitivity analyses, which also confirmed that olanzapine was the dominant strategy following the base-case findings. Conclusions: By comparison with risperidone, the model suggests that olanzapine can be regarded as a cost-effective therapeutic strategy for the management of patients with behavioural and psychological symptoms in Thailand.

Trachsummaroma is an eye infectious disease caused by Chlamydia Trachomatis bacterium, which may lead to irreversible blindness. The disease is spread directly or indirectly by contacting a contaminated material. It can also be transmitted through the disease vector known as “Musca sorbens” or “Bazaar fly”. To curtail the spread of the disease in a population, a meaningful information on the spread and possible control of the disease is required. Mathematical modeling provides efficient tools that can be used to understand and analyze the dynamics of the disease and its control. Several compartmental epidemic models have been proposed in the literature to study the dynamics of trachoma; including SI, SIR and SEIR. However, majority of the existing trachoma models consider only person to person transmission. Thus, the information provided by such models is insufficient since they did not capture the disease vector transmission. The current study proposed a novel SEIR-SEI model that consider both person-person and vector transmission dynamics. The threshold quantity, basic reproduction number R0 is obtained using the next generation matrix, and it was proved that the disease-free equilibrium is asymptotically stable when R0 < 1, and the endemic equilibrium is globally asymptotically stable when R0 > 1. Some simulation results with the aid of mesh plots for the reproductive number as a function of two different biological parameters were obtained. Furthermore, a comprehensive sensitivity analysis is conducted to identify the influence of the individual parameters on the R0. Numerical results show that the vector contact rate has the highest sensitivity with respect to R0, and the value of R0 increases with increase in, hence, the disease can be controlled by decreasing the vector contact rate. Similarly, improving the rate of environmental hygiene and facial cleanliness will decrease the size of R0 and result in the declination of the disease transmission. Moreover, a detailed parameter estimation of the model parameters and model fitting was presented with the use of field data cases from Northern Nigeria using least-square fitting method. The study provides alternative tools that can be used for planning trachoma control program to achieve global eradication of trachoma as a public heath challenge as targeted by WHO in 2030.

Studies performed at single-cell resolution have demonstrated the physiological significance of cell-to-cell variability. Various types of mathematical models and systems analyses of biological networks have further been used to gain a better understanding of the sources and regulatory mechanisms of such variability. In this work, we present a novel sensitivity analysis method, called molecular density function perturbation (MDFP), for the dynamical analysis of cellular heterogeneity. The proposed analysis is based on introducing perturbations to the density or distribution function of the cellular state variables at specific time points, and quantifying how such perturbations affect the state distribution at later time points. We applied the MDFP analysis to a model of signal transduction pathway involved in TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in HeLa cells. The MDFP analysis showed that caspase-8 activation regulates the timing of the switch-like increase of cPARP (cleaved poly(ADP-ribose) polymerase), an indicator of apoptosis. Meanwhile, the cell-to-cell variability in the commitment to apoptosis depended on mitochondrial outer membrane permeabilization (MOMP) and events following MOMP, including the release of Smac (second mitochondria-derived activator of caspases) and cytochrome-C from mitochondria, the inhibition of XIAP (X-linked inhibitor of apoptosis) by Smac and the formation of apoptosome.

The current work investigates how adding a battery of optimal capacity to a grid-connected photovoltaic (PV) system can improve its economic feasibility. Also, the effect of different parameters on the feasibility of the PV system was evaluated. The OBC was determined for different saving targets of the annual electricity consumption of the chosen building. For this aim, real electricity consumption data of a residential building in Landskrona, Sweden, was used as energy consumption profile. Solar World SW325XL, which is a monocrystalline solar panel, was selected as PV panels. The calculations were performed under the metrological and economic conditions of southern Sweden. Different working parameters (WP)were considered (prices of the battery, feed-in tariffs, and saving targets). The performed calculations show that the optimal battery capacity (OBC), in which the payback time (PBT) of the system is maximized, strongly depends on the WP. The proper selection of the battery can considerably increase the economic feasibility of the PV system in southern Sweden. However, in some cases, using battery can have a negative impact on the PBT of the system. The results show that the electricity price, the module price, the inverter price, and the inverter lifetime have the highest effect on the PBT.

The function of sleep in mammal and other vertebrates is one of the great mysteries of biology. Many hypotheses have been proposed, but few of these have made even the slightest attempt to explain the essence of sleep - the uncompromising need for reversible unconsciousness. During sleep, epiphenomena - often of a somatic character - occur, but these cannot explain the core function of sleep. One answer could be hidden in the observations made for long periods of time of the function of the central nervous system (CNS). The CNS is faced with conflicting requirements on stability and excitability. A high level of excitability is desirable, and is also a prerequisite for sensitivity and quick reaction times; however, it can also lead to instability and the risk of feedback, with life-threatening epileptic seizures. Activity-dependent negative feedback in neuronal excitability improves stability in the short term, but not to the degree that is required. A hypothesis is presented here demonstrating how calibration of individual neurons - an activity which occurs only during sleep - can establish the balanced and highest possible excitability while also preserving stability in the CNS. One example of a possible mechanism is the observation of slow oscillations in EEGs made on birds and mammals during slow wave sleep. Calibration to a genetically determined level of excitability could take place in individual neurons during the slow oscillation, so that action potentials are generated during the oscillations “up-phase”. This can only take place offline, which explains the need for sleep. The hypothesis can explain phenomena such as the need for unconsciousness during sleep, with the disconnection of sensory stimuli, slow EEG oscillations, the relationship of sleep and epilepsy, age, the effects of sleep on neuronal firing rate and the effects of sleep deprivation and sleep homeostasis. This is with regard primarily to mammals, including humans, but also all other vertebrates.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

Typhoid fever is a major public health burden which causes substantial global morbidity and mortality due to lack of decisive diagnostic protocols. The capacity of commonly use diagnostic test to validate the absence of typhoid fever is controversial. This study explores to evaluate new techniques for typhoid diagnosis and proposed a harmonised suitable standardized composite reference to be adopted. Published peer-reviewed articles indexed in PubMed, MEDLINE and Google scholar were reviewed for hospital-based studies. This study reveals new typhoid diagnostic techniques such as proteomics, serology, Rapid Diagnostic tests (RDTs), transcriptomics, genomics, and metabolomics. 34.4% of the studies use prospective study design. The study result establishes that, Widal test has a moderate diagnostic accuracy with average percentage sensitivity (52.9%), specificity (54%), positive predictive value (PPV) (56.8%) as well as negative predictive value (NPV) (55.6%) when compared with 29.4%, 28%, 29.5%, and 27.8% of Typhidot respectively. The findings showed a statistically significant difference on the sensitivity between Widal and Typhidot t (40) = 2.639, p = 0.012 at p<0.05 using independent sample t-test. When there is no perfect reference standard that has an optimal diagnostic accuracy, the need for a harmonised suitable standardized composite reference is essential. Hence, this study recommends that, peripheral blood culture with established sensitivity of 60% and Widal test with average sensitivity of 52.9% be adopted as a consensus composite reference standard for typhoid fever diagnosis in other to improve confidence in prevalence estimates.

A novel characterization method for discrete saw filters vibrational sensitivity is presented. The proposed approach allows the characterization of filters under vibrations and the extraction of a behavioural model. Filters are assumed to be transducers so that external induced vibrational energy is partially transformed in a undesired simultaneous amplitude and phase modulation of the input RF signal. When the filter is mechanically excited with vibrations, it introduces spurious amplitude and phase modulation to the input signal that can potentially affect the link quality.

Accurate monthly runoff estimation is fundamental in water resources management, planning, and development, resulting in preventing and reducing water-related problems, such as flooding and drought. This article evaluates the performance of the monthly hydrological rainfall-runoff model, GR2M model, in Thailand's southern basins. The GR2M model requires only two parameters, and no prior research has been reported on its application in this region. The 37 runoff stations, which are distributively located in three sub-watersheds of Thailand's southern region, namely; Thale Sap Songkhla, Peninsular-East Coast, and Peninsular-West Coast, were selected as study cases. The available monthly hydrological data of runoff, rainfall, air temperature from the Royal Irrigation Department (RID) and the Thai Meteorological Department (TMD) were collected and analyzed. Thornthwaite method was utilized for the determination of evapotranspiration. The model's performance was conducted using three statistical indices: Nash-Sutcliffe Efficiency (NSE), Correlation Coefficient (r), and Overall Index (OPI). The model's calibration results for 37 runoff stations gave the average of NSE, r, and OPI of 0.637, 0.825, and 0.757, and those values for verification of 0.465, 0.750, and 0.639, respectively. It indicated a model's acceptable performance and could apply the GR2M model for determining monthly runoff variation in this region. The spatial distribution of X1 and X2 values was conducted by using IDW method. It was susceptible to the X1 value and X2 value of approximately more than 0.90 gave the higher model's performance.

Background: Flow-through dot-blot assay (FT-DBA) for SARS-CoV-2 specific IgG detection will provide a reliable and affordable immunoassay for the rapid serosurveillance against COVID-19. Method: SARS-CoV-2 antigens were immobilized on nitrocellulose membrane to capture IgG immunoglobulins, which were then detected with AuNP anti-human IgG. A total of 181 samples were characterized with in-house and commercial immunoassay. The positive panel consisted of RT-PCR positive samples from patients with both <14 days and >14 days from the onset of symptoms, while the negative panel contained samples collected either from the pre-pandemic era dengue patients from healthy donors during the pandemic period. Results: In-house ELISA selected a total of 79 true seropositive and 100 seronegative samples. The sensitivity of samples with <14 days using FT-DBA was 94.7% which increased to 100% for samples >14 days. The overall detection sensitivity and specificity were 98.8% and 98%, respectively, whereas the overall PPV and NPV were 97.6% and 99%. Moreover, comparative analysis between ELISA and FT-DBA revealed clinical agreement of Cohen’s Kappa value of 0.944. Conclusion: The assay can confirm past SARS-CoV-2 infection with high accuracy within 2 minutes compared to ELISA. It can help track SARS-CoV-2 disease progression, population screening, and vaccination response.

Equilibrium climate sensitivity (ECS) is the change in global mean temperature expected to result from doubling atmospheric CO2 concentration from pre-industrial levels. Extensive research during the past 40 years has not reduced the uncertainty associated with ECS. Sherwood et al. [1] applied Bayesian statistics to evidence from climate-process physics, historical observations and earlier proxies to reduce the range of ECS from 1.5 – 4.5 K to 2.6 – 4.1 K. This paper examines their methods and many of the assumptions they made. It also evaluates two additional periods in the Holocene to show that factors other than CO2 drove recent climate change. It identifies potential systematic errors resulting from adding non-equilibrium short-term adjustments to the radiative forcing of greenhouse gases and from underestimating the effects of solar irradiance, ocean currents and aerosols. These factors have resulted in estimates of the forcing by CO2 that far exceed the apparent effects in paleoclimate data.

The effect of sensitivity points (sequence order and position of every element) of sequences following comparative optinalysis under two proposed mechanisms, the paranodic and synodic skewization, was studied to develop a modeling approach to comparative optinalysis of sequences. The results show that the outcomes of comparative optinalysis (similarity measurement) in a set of paranodically skewed sequences can be modeled deterministically by suitable line regression functions. The sensitivity points (nodes) of a sequence display two important and distinct zones, the K-zones and the B-zones. Continues paranodic skewization within these zones (KB zones) operates within probability space, but at hyperskewization level and at the K-zones only, the outcomes of comparative optinalysis operate outside the probability space. Moreover, the outcomes of comparative optinalysis by synodic skewization can be modeled deterministically by some regression line functions, but a general regression function cannot be identified. At certain limit of skewization value space, following paranodic and synodic skewization, the outcomes of comparative optinalysis at the left-sided sequence form a similar pattern with the right-sided sequence.

Densimetric Froude (Fr) is the minimum velocity required to prevent sediment deposition in pipes. Prediction of Fr is of utmost importance in numerous applications in civil engineering. In this paper through using a new hybrid method. Genetic Algorithm (GA) is used for optimum selection of membership functions of Adaptive Neuro-Fuzzy Inference System (ANFIS), and Singular Value Decomposition (SVD) method is used to compute the linear parameters of ANFIS’s results section (ANFIS-GA/SVD). Also, two different target functions are known as training error (TE) and prediction error (PE) by Pareto curve, the trade-off between these functions is selected as the optimal modeling point. First, different models will be presented using the parameters affecting Fr prediction, classifying them in different groups; then the Fr parameter will be predicted for all the different models through utilizing three different sets of data and the ANFIS-GA/SVD technique. The results of the models indicate that the best Fr prediction is obtained when independent parameters such as volumetric sediment concentration (CV), ratio of median diameter of particle size to pipe diameter (d/D), ratio of median diameter of particle size to hydraulic radius (d/R) and overall friction factor of sediment (λs) use as input variables in prediction of Fr. A sensitivity analysis is also conducted for the purpose of examining the effect of each of the dimensionless parameters on Fr prediction accuracy. Comparing the results of the suggested models with the existing regression-based equations shows that ANFIS-GA/SVD (R²=0.986, MAPE=4.397, RMSE=0.206, SI=0.053, ρ=0.026, BIAS=-0.025) is more accurate than the rest of the models.

SLEUTH Model (slope, landuse, exclusion, urban extent, transportation and hillshade) is an important tool for landuse planning and land policy. To evaluate the performance of SLEUTH model, implementation of Sensitivity Analysis (SA) is essential. The main limitation of SA in SLEUTH application is a lack of insight into model input self-modification parameters (SMPs) variation, namely, uncertainty involved in the model transfer metrics and model presumptions, which often misled the decision makers and model users. To address this issue, this study divided the forward process into two stages. Firstly, during the transfer process ①, the contribution scores of five SMPs were drawn, and parameters highly sensitive to model output were given. Apart from that, the recommended initial value for SMPs of 0.11, 0.2, 0.87, 1.13, 15, 1.01, 0.49 were found to be subordinated to such a heterogeneous urban area simulation. Secondly, during the transfer process ②, SMP caused imagery metrics indicated the disparity between parameters with Fixed Reference and with Successive Reference. Reversely, it derives reasonable threshold for the best fit values of five prediction coefficients’ initialization by comparing the real image with the predicted one. The framework of SLEUTH model transfer mechanism not only could distinguish highly sensitive SMPs with higher contribution scores, but also could give parametric analysis for simulation imagery based on metrics. The study was found to be a practical tool for quantization response of model input variables for modelling complex urban systems. So, this insight can help geographic information scientists decide how to find out the inner forward transfer mechanism of SLEUTH model for further make good use of it and improve the model.

Metformin, the treatment of first choice in type 2 diabetes (T2D), is known to mainly act by decreasing endogenous glucose production (EGP) in the liver. Paradoxically, in the last decade several reports documented increased EGP after metformin treatment. This increase, was often attributed to pronounced rises in glucagon, consistent with counter-regulatory response to the glucose lowering effect of metformin. However, considering that hyperglucagonemia, but not hypoinsulinemia, is a main driver of EGP in T2D, increased EGP should have been a common finding. This observation, together with the finding that metformin antagonizes glucagon effects on energy expenditure and protein synthesis, concurrently to its effects on EGP and the emerging evidences demonstrating increased branched chain and gluconeogenic amino acids in response to metformin treatment may points to a liver alpha-cell skeletal muscle cross talk similar to that observed in the liver-alpha cell axis. Here, we provide a mechanistic perspective to this latter possibility, based on mechanistic studies of metformin’s transcriptional targets; retaining thus its glucagon antagonistic and presumably anti-gluconeogenic effects on liver and attributing the increase in EGP to renal gluconeogenesis. We finally discuss how increased EGP might reflect an adverse response to metformin treatment, providing support from clinical and epidemiological data.

Around 14% of the global population does not have access to electricity. About 95% of those are living in rural Sub-Saharan Africa. Often in these regions, diesel generators are the only source of electricity. The operating cost of these diesel generators is high. However, solar and wind energy are available in most of African countries. This study presents the analysis of designing an off-grid hybrid system with a wind turbine, PV, diesel generator, and battery to power a hospital, school, and 200 household village in four locations across Somalia. The research investigated the availability of wind-solar resources in selected locations. Designing of the system and economic-technical calculations were performed using HOMER. The selection of the optimum design was based on the Cost of Electricity and Net Present Cost. The results show that for Kabaal and Ceel Buur, a WT-PV-DG-Battery is the optimal system as the wind resource in these regions is high. For Saakov and Baki, a PV-DG-Battery system proves to be optimum as the wind resource is limited here. The study also evaluated the control strategy and proved that combined dispatch was the most cost-effective for these locations. The study concluded that hybrid systems are more economical than diesel systems.

Despite increased global interest in the impacts of natural disasters on tourism, less study executes exploring how tourism sensitivity is addressed at the destination level. Generating a link between tourism and natural disaster management is vital in places that rely heavily on tourism and are prone to natural hazards. Ranau, Sabah (Malaysia) is one of the disaster-prone tourists' destination area. Hence, this paper applies the case study of Ranau earthquake 2015 to explore tourism sensitivity towards natural disasters. A qualitative of in-depth interview is applied to acquire information needed from the Ranau tourism entrepreneurs and operators. To analyse the qualitative data, a thematic analysis is conducted. Overall findings show that tourism activity in Ranau are identified to be sensitive towards the 2015 earthquake with a significant percentage of sensitivity level on two elements. These elements are known as Source and Power. The Source element includes tourism products, size of business, development, and natural disasters management with a significant sensitivity compared to the Power element (social capital). This provides insight to the need of specific tourism system adaptation as response to the earthquake and considering the integration of natural disaster management into tourism development to enhance long term sustainability.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

Hydrologic models are conventionally constrained and evaluated using point measurements of streamflow, which represents an aggregated catchment measure. As a consequence of this single objective focus, model parametrization and model parameter sensitivity are typically not reflecting other aspects of catchment behavior. Specifically for distributed models, the spatial pattern aspect is often overlooked. Our paper examines the utility of multiple performance measures in a spatial sensitivity analysis framework to determine the key parameters governing the spatial variability of predicted actual evapotranspiration (AET). Latin hypercube one-at-a-time (LHS-OAT) sampling strategy with multiple initial parameter sets was applied using the mesoscale hydrologic model (mHM) and a total of 17 model parameters were identified as sensitive. The results indicate different parameter sensitivities for different performance measures focusing on temporal hydrograph dynamics and spatial variability of actual evapotranspiration. While spatial patterns were found to be sensitive to vegetation parameters, streamflow dynamics were sensitive to pedo-transfer function (PTF) parameters. Above all, our results show that behavioral model definition based only on streamflow metrics in the generalized likelihood uncertainty estimation (GLUE) type methods require reformulation by incorporating spatial patterns into the definition of threshold values to reveal robust hydrologic behavior in the analysis.

Earth's global surface temperature shows variability on an extended range of temporal scales and satisfies an emergent scaling symmetry. Recent studies indicate that scale invariance is not only a feature of the observed temperature fluctuations, but an inherent property of the temperature response to radiative forcing, and a principle that links the fast and slow climate responses. It provides a bridge between the decadal- and centennial-scale fluctuations in the instrumental temperature record, and the millennial-scale equilibration following perturbations in the radiative balance. In particular, the emergent scale invariance makes it possible to infer equilibrium climate sensitivity (ECS) from the observed relation between radiative forcing and global temperature in the instrumental era. This is verified in ensembles of Earth system models (ESMs), where the inferred values of ECS correlate strongly to estimates from idealized model runs. For the range of forcing data explored in this paper, the method gives best estimates of ECS between 2.3 and 3.4 K.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based studies using these datasets require thoughtful modification to sample selection and analytic strategies, relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings. This paper offers some practical guidance to the full analytical process, demonstrates methods for estimating causal treatment effects on several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying repeated measures outcomes, and aims to increase transparency and reproducibility. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

Systematic traders employ algorithmic strategies to manage their investments. As a result of the deterministic nature of such strategies, it is possible to determine their exact responses to any conceivable set of market conditions. Consequently, sensitivity analysis can be conducted to systematically uncover undesirable strategy behavior and enhance strategy robustness by adding controls to reduce exposure during periods of poor performance / unfavorable market conditions or increase exposure during periods of strong performance / favorable market conditions. In this study, we formulate both a simple systematic trend-following strategy (i.e., trading model) to simulate investment decisions, and a market model to simulate the evolution of instrument prices. We then map the relationship between market model parameters under various conditions and strategy performance. We focus, in particular, on identifying the performance impact of changes in both serial dependence in price variability and changes in the trend. The long-range serial dependence of the true range worsens performance of the simple classic trend-following strategy. During periods of strong performance, the dispersion of trading outcomes increases significantly as long-range serial dependence increases.

We applied a framework to assess climate change vulnerability of 52 major vegetation types in the western United States to provide spatially-explicit input to adaptive management decisions. The framework addressed climate exposure and ecosystem resilience; the latter derived from analyses of ecosystem sensitivity and adaptive capacity. Measures of climate change exposure used observed climate change (1981-2014) and then climate projections for the mid-21st century (2040-2069 RCP 4.5). Measures of resilience included (under ecosystem sensitivity) landscape intactness, invasive species, fire regime alteration, and forest insect & disease risk, and (under adaptive capacity), measures for topo-climate variability, diversity with functional species groups, and vulnerability of any keystone species. Outputs are generated per 100km² hexagonal area for each type. As of 2014, moderate climate change vulnerability was indicated for >50% of the area of 50 of 52 types. By the mid-21^st century, all but 19 types face high or very high vulnerability with >50% of the area scoring in these categories. Measures for resilience explain most components of vulnerability as of 2014, with most targeted vegetation scoring low in adaptive capacity measures and variably for specific sensitivity measures. Elevated climate exposure explains increases in vulnerability between the current and mid-century time periods.

Direct Behavior Rating (DBR) as a behavioral progress monitoring tool can be designed as longitudinal assessment with only short intervals between measurement points. The reliability of these instruments has been evaluated mostly in observational studies with small samples based on generalizability theory. However, for standardized use in the pedagogical field, a larger and broader sample is required in order to assess measurement invariance between different participant groups and over time. Therefore, we constructed a DBR with multiple items to measure the occurrence of specific externalizing and internalizing student classroom behaviors on a Likert scale (1 = never to 7 = always). In a pilot study, two trained raters observed 16 primary school students and rated the student behavior over all items with a satisfactory reliability. In the main study, 108 regular primary school students, 97 regular secondary school students and 14 students in a clinical setting were rated daily over one week (five measurement points). IRT analyses confirmed the instrument’s technical adequacy, and latent growth models demonstrated the instrument’s stability over time. Further development of the instrument and study designs to implement DBRs are discussed.

In a limestone quarry mine, fragmentation is a crucial outcome of blasting operations. The optimization of blasting operations greatly benefits from the prediction of rock fragmentation. The main factors that affect fragmentation are rock mass characteristics, blast geometry, and explosive properties. This paper is a step towards the implementation of machine learning and deep learning algorithms for predicting the extent of fragmentation (in percentage) in opencast mining. Various parameters can affect fragmentation. But, in this paper initially, ten parameters (spacing, drill hole diameter, burden, average bench height, powder factor, number of holes, charge per delay, uniaxial compressive strength, specific drilling, and stemming) are collected to train the model. However, due to a weak correlation with rock fragmentation, drill diameter, Average bench height, compressive strength, stemming, and charge per delay are eliminated to reduce model complexity. A total of 219 data sets having five input features i.e., the number of holes, spacing, burden, specific drilling, and powder factor are used to develop the models. To predict rock fragmentation due to blasting in limestone quarry mines, both machine learning models (Random Forest Regression (Bagging), Support Vector Regression, and XG Boost Regression (Boosting)), as well as a deep learning model (Neural Network Regression), are applied to develop a model that can optimize the prediction of fragmentation. The Artificial neural network model optimization showed that the model with architecture 64-32-16-1 can perform well giving MSE (mean squared error) values of 41.32 and 28.59 on training and test data respectively. The R2 value for both training and test is 0.83. Random Forest regression is also performing well compared to SVR and XG boost with the MSE value 12.37 and 9.89 on training and testing data respectively. Here, the R2 value for both sets are 94%. Based on the permutation importance and Shapely plot values, the powder factor has the highest impact, and the burden has the lowest impact on fragmentation.

Study objective Since December 2019, the coronavirus disease (COVID-19) pandemic has caused over a million deaths and resulted in adverse socio-economic impacts worldwide. However, predictability and prognostication of clinical features vary among different populations. Methods We search PubMed, EMBASE, Cochrane Library, Google Scholar, and WHO Global Health Library from December 2019 to April 2020 for studies reporting the risk factors, clinical features, and outcomes. The random-effect models for transformed prevalence (single-arm) or bivariate random-effect models (sensitivity and specificity) for correlated performance indicators. Results Among the 189 included studies representing 53,659 patients, the most sensitive predictor for COVID-19 infection was fever in adults (83%, 95% confidence interval [CI]:73–90%), and the most specific predictor was fatigue (96%, 95% CI: 80–99%). Fever was the most sensitive symptom in predicting the severity (89%, 95% CI:83–92%), followed by cough (71%, 95% CI:63–78%). The most specific predictor of severe COVID-19 was a chronic obstructive pulmonary disease (99%, 95% CI:98–99%). The stage of the outbreak and age significantly affect the prevalence of fever, fatigue, cough, and dyspnea. Fever, cough, fatigue, hypertension, and diabetes mellitus combined have a 3.06 positive likelihood ratio (PLR) and a 0.59 negative likelihood ratio (NLR) in the diagnosis. Additionally, fever, cough, sputum production, myalgia, fatigue, and dyspnea combined have a 10.44 PLR and a 0.16 NLR in predicting severe COVID-19. Conclusions Understanding the different distribution of predictors essential for screening potential COVID-19 infection and severe outcomes and the combination of symptoms could improve the pre-test probability.

The ability to smell is crucial for most species as it enables the detection of environmental threats like smoke, fosters social interactions, and contributes to the sensory evaluation of food and eating behavior. The high prevalence of smell disturbances throughout the life span calls for a continuous effort to improve tools for quick and reliable assessment of olfactory function. Odor-dispensing pens, called Sniffin' Sticks, are an established method to deliver olfactory stimuli during diagnostic evaluation. We tested the suitability of a Bayesian adaptive algorithm (QUEST) to estimate olfactory sensitivity using Sniffin' Sticks by comparing QUEST sensitivity thresholds with those obtained using a procedure based on an established standard staircase protocol. Thresholds were measured twice with both procedures in two sessions (Test and Retest). Overall, both procedures exhibited considerable overlap with QUEST displaying slightly higher test-retest correlations, less variability between measurements, and reduced testing duration. Notably, participants were more frequently presented with the highest concentration during the QUEST which may foster adaptation and habituation effects. We conclude that further research is required to better understand and optimize the procedure for assessment of olfactory performance.

Magneto-optic surface plasmon resonance (MOSPR) based sensors are highly attractive as next generation biosensors. However, these sensors suffer from oxidation leading to degradation of performance, reproducibility of the sensor surface because of the difficulty of removing adsorbed materials, and degradation of sensor surface during surface cleaning, and these limit their applications. In this paper, I propose MOSPR-based biosensors with 0 to 15 nm thick inert polycarbonate laminate plastic as a protective layer and theoretically demonstrate the practicability of our approach in water-medium for three different probing samples: ethanol, propanol, and pentanol. I also investigate microstructure and magnetic properties. The chemical composition and layered information of the sensor are investigated using X-ray reflectivity and X-ray diffraction analyses and these show distinct fcc-Au (111) phases, as dominated by the higher density of conduction electrons in Au as compared to Co. The magnetic characterization measured with the in-plane magnetic field to the sensor surface for both the as-deposited and annealed multilayers showed isotropic easy axis magnetization parallel to the multilayer interface at a saturating magnetic field of <100 Oe. The sensor showed a maximum sensitivity of 5.5 × 10⁴%/RIU for water-ethanol media and the highest detection level of 2.5 × 10⁻⁸ for water-pentanol media as the protective layer is increased from 0 to 15 nm.c

Immunostaining is an essential histochemical technique for analyzing pathogenesis and making a histopathological diagnosis. The needs are prompted by technical development and refinement, commercial availability of a variety of antibodies, deepened knowledge of immunohistochemical markers, accelerated analysis of morphofunctional correlations, progress in molecular target therapy, and the expectation of advanced histopathological diagnosis. However, immunostaining does have various pitfalls and caveats. We should learn from mistakes and failures, as well as from false positivity and false negativity. The present review article describes various devices, technical hints and trouble-shooting guides to keep in mind in performing immunostaining.

The characteristics of the eddy mass transport are estimated depending on the values of the parameters of a large-scale flow that forms under the conditions of the shelf seas in the Arctic. For this, the results of numerical simulation of the Kara Sea with a horizontal resolution permitting the development of mesoscale eddies are used. The parameters resulting from numerical experiment are considered as a statistical sample and are analyzed using methods of sensitivity study and clustering of sample elements. Functional dependencies are obtained that are closest to the simulated distributions of quantities. These expressions make it possible, within the framework of large-scale models, to evaluate the characteristics of the cross-isobatic eddy mass transport in the diffusion approximation with a counter-gradient flux. Numerical experiments using the SibCIOM model showed that areas along the Fram branch of the Atlantic waters trajectory in the Arctic as well as the shelf of the East Siberian and Laptev seas with adjacent deep water areas are most sensitive to proposed parameterization of eddy exchanges. Accounting for counter-gradient eddy fluxes turned out to be less important.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

CO2 injection into geological formations is considered one way of mitigating the increasing levels of carbon dioxide concentrations in the atmosphere and its effect on and global warming. In regard to sequestering carbon underground, different countries have conducted projects at commercial scale or pilot scale and some have plans to develop potential formations for carbon dioxide storage. In this study, pure CO2 injection is examined on a model with the properties of bunter sandstone and then sensitivity analyses were conducted for some of the important parameters. The results of this study show that the extent to which CO2 has been convected in the porous media in the reservoir plays a vital role in improving the CO2 dissolution in brine and safety of its long term storage. We conclude that heterogeneity plays a crucial role on the saturation distribution and can increase or decrease the amount of dissolved CO2 in water. Furthermore, the value of absolute permeability controls the effect of the Kv/Kh ratio on the CO2 dissolution in brine. In other words, as the value of vertical and horizontal permeability decreases (i.e. tight reservoirs) the impact of Kv/Kh ratio on the dissolved CO2 in brine becomes more prominent. Additionally, reservoir engineering parameters, such as well location, injection rate and scenarios, also have a high impact on the amount of dissolved CO2.

This brief note aims to explain the scope in conducting large-scale serological surveys of SARS-CoV-2 to define the landscape of population immunity without overlooking the inherent uncertainty steaming from sampling design and diagnostic validity. The note completes with a succinct statistical appendix of simple methods for estimating prevalence from random population samples using imperfect diagnostic tests.

This paper proposes a model based on gene expression programming for predicting discharge coefficient of triangular labyrinth weirs. The parameters influencing discharge coefficient prediction were first examined and presented as crest height ratio to the head over the crest of the weir (p/y), crest length of water to channel width (L/W), crest length of water to the head over the crest of the weir (L/y), Froude number (F=V/√(gy)) and vertex angle () dimensionless parameters. Different models were then presented using sensitivity analysis in order to examine each of the dimensionless parameters presented in this study. In addition, an equation was presented through the use of nonlinear regression (NLR) for the purpose of comparison with GEP. The results of the studies conducted by using different statistical indexes indicated that GEP is more capable than NLR. This is to the extent that GEP predicts the discharge coefficient with an average relative error of approximately 2.5% in such a manner that the predicted values have less than 5% relative error in the worst model.

Land consolidation engineering inevitably interferes with terrestrial ecosystems, leading to natural capital loss. Therefore, conducting an ecological sensitivity evaluation of a project area before consolidation engineering is very important for reducing unnecessary human interference. Conservation of terrestrial ecosystems and the biodiversity therein to the greatest possible extent is urgently needed. This research analyzes the interference by human activities caused by land consolidation engineering in terrestrial ecosystems. GIS technology, ecological values, landscape pattern indexes, and an ecological risk evaluation were used to construct an ecological sensitivity evaluation index. The coefficient of variation method and a comprehensive sensitivity rating evaluation were used to calculate the weights and results. The project area was divided into sensitivity zones according to the results, and the results and suggestions are as follows: In the highly eco-sensitive zone, where bare rocks, gravel, and grass-covered areas compose the main landscape type, vegetation should be restored, and forests should be planted. In the medium eco-sensitivity zone, where irrigated paddy fields and arid land compose the main landscape type, land parcels should be merged, and agricultural infrastructure should be constructed or improved. In the low eco-sensitivity zone, where forests compose the main landscape type, roads should be closed, natural habitat should be restored, and buffer zones should be created. This study provides suggestions for future land management decisions.

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. Currently, a major persisting problem is to cherry pick the combinations based on expert advice, literature survey or guesses for investigation. This entails investment in time, energy and expenses at various levels of research. To address these issues, a search engine design was recently been developed, which showed promise by revealing existing confirmatory published wet lab results. Additionally and of import, the engine mined up a range of unexplored/untested/unknown combinations of genetic factors in the Wnt pathway that were affected by ETC-1922159 enantiomer, a PORCN-WNT inhibitor, after the colorectal cancer cells were treated with the inhibitor drug. As an example, MYC is known to upregulate PRC2 complex. PRC2 complex contains EZH2, which suppresses tumor suppressor genes via epigenetic modifications. MYC and HOXB8 are up regulated in colorectal cancer, however, the dual working mechanism of the same is not known. The in silico engine showed positioning which correctly approximates and assigns to this 3rd order combination of MYC-HOXB8-EZH2, pointing to the in vitro/in vivo down regulation by ETC-1922159. If the protein interaction of MYC-HOXB8 can be established and a study be done apropos EZH2, it will establish at in vitro/in vivo level, the in silico ranking also. The potential of this engine is immense given the problem faced in biology and other fields. Here we elucidate the R code to understand the mechanics of the search engine in a fluid manner for systems biologists. Though the search engine is in the developmental stage, we share the detailed mechanism of the working principles of the same as it can be generalized to problems in other fields.

The active debate about the processes governing the organic-rich sediment deposition generally involves the relative roles of elevated primary productivity and enhanced preservation related to anoxia. However, other less spotlighted factors could have a strong impact on such deposits: e.g. residence time into the water column (bathymetry), sedimentation rate, transport behavior of organo-mineral floccules on the sea floor. They are all strongly interrelated and may be obscured in the current conceptual models inspired from most representative modern analogues (i.e. upwelling zones and stratified basins). To improve our comprehension of organic matter distribution and heterogeneities, we conducted a sensitivity analysis on the processes involved in organic matter production and preservation which have been simulated within a 3D stratigraphic forward model. The Lower-Middle Toarcian of the Paris Basin was chosen as a case study as it represents one of the best documented example of marine organic matter accumulation. The relative influence of the critical parameters (bathymetry, diffusive transport, oxygen mixing rate and primary production) on the output parameters (Total Organic Carbon, and oxygen level), determined performing a Global Sensitivity Analysis, shows that, in the context of a shallow epicontinental basin, a moderate primary productivity (> 175 gC.m^-².yr^-1) can led to local anoxia and organic matter accumulation. We argue that, regarding all the processes involved, the presence and distribution of organic-rich intervals is linked as a first-order parameter to the morphology of the basin (e.g. ramp slope, bottom topography). These interpretations are supported by very specific ranges of critical parameters which allowed to obtain output parameter values in accordance with the data. This quantitative approach and its conclusions open new perspectives about the understanding of global distribution and preservation of organic-rich sediments.

Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer screening. Consequently, the detection of ctDNA in liquid biopsy gains much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from the industry. However, traditional gene detection technology is difficult to achieve low cost, real-time and portable measurement of ctDNA. Electroanalytical biosensors have many unique advantages such as high sensitivity, high specificity, low cost and good portability. Therefore, this review aims to discuss the latest development of biosensors for minimal-invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, detection strategies and figures of merit. Aiming at the portable, real-time and non-destructive characteristics of biosensors, we analyze their development in the Internet of Things, point-of-care testing, big data and big health.

Recent evidence suggests the existence of shared neural resources for rhythm processing in language and music. Such overlaps could be the basis of the facilitating effect of regular musical rhythm on spoken word processing previously reported for typical children and adults, as well as adults with Parkinson’s disease and children with developmental language disorders. The present study builds upon these previous findings by examining whether musical rhythmic priming also influences visual word processing, and the extent to which such cross-modal priming effect of rhythm is related to individual differences in musical aptitude and reading skills. EEG was recorded while participants listened to a rhythmic tone prime, followed by a visual target word with a stress pattern that either matched or mismatched the rhythmic structure of the auditory prime. Participants were also administered standardized assessments of musical aptitude and reading achievement. ERPs elicited by target words with a mismatching stress pattern showed an increased fronto-central negativity. Additionally, the size of the negative effect correlated with individual differences in musical rhythm aptitude and reading comprehension skills. Results support the existence of shared neurocognitive resources for linguistic and musical rhythm processing, and have important implications for the use of rhythm-based activities for reading interventions.

Determination of the presence in the blood of antibodies specific to the causative agent of a particular disease (serodiagnosis) is an effective approach in medical analytical chemistry. Serodiagnostics performed in the lateral flow immunoassay format (immunochromatography) meet the modern requirements for point-of-care testing and are supported by existing technologies of large-scale diagnostic tests production—thus raising increased attention in a tense epidemiological situation. For traditional lateral flow serodiagnostics formats, a large number of nonspecific immunoglobulins in the sample significantly reduces the degree of detectable binding. To overcome these limitations, an assay based on the formation of immobilized antigen— specific antibody—labeled antigen complexes detection was proposed. However, the requirements for its implementation, providing maximum sensitivity, have not been established. This article describes the mathematical model for the above assay. The influence of the ratio of reagent concentrations on the analysis results is considered. It is noted that the formation of specific antibody complexes with several labeled antigens is the main limiting factor in reducing the detection limit, and methods are proposed to minimize this factor. Recommendations for the choice of the assay conditions, following from the analysis of the model, are confirmed experimentally.

An iterative outlier elimination procedure based on hypothesis testing, commonly known as Iterative Data Snooping (IDS) among geodesists, is often used for the quality control of the modern measurement systems in geodesy and surveying. The test statistic associated with IDS is the extreme normalised least-squares residual. It is well-known in the literature that critical values (quantile values) of such a test statistic cannot be derived from well-known test distributions, but must be computed numerically by means of Monte Carlo. This paper provides the first results about Monte Carlo-based critical value inserted to different scenarios of correlation between the outlier statistics. From the Monte Carlo evaluation, we compute the probabilities of correct identification, missed detection, wrong exclusion, overidentifications and statistical overlap associated with IDS in the presence of a single outlier. Based on such probability levels we obtain the Minimal Detectable Bias (MDB) and Minimal Identifiable Bias (MIB) for the case where IDS is in play. MDB and MIB are sensitivity indicators for outlier detection and identification, respectively. The results show that there are circumstances that the larger the Type I decision error (smaller critical value), the higher the rates of outlier detection, but the lower the rates of outlier identification. For that case, the larger the Type I Error, the larger the ratio between MIB and MDB. We also highlight that an outlier becomes identifiable when the contribution of the measures to the wrong exclusion rate decline simultaneously. In that case, we verify that the effect of the correlation between the outlier statistics on the wrong exclusion rates becomes insignificant from a certain outlier magnitude, which increases the probability of identification.

The inaccurate estimates of linear prediction coefficient (LPC) and noise variance introduce bias in Kalman filter (KF) gain and degrades speech enhancement performance. The existing methods proposed a tuning of the biased Kalman gain particularly in stationary noise condition. This paper introduces a tuning of the KF gain for speech enhancement in real-life noise conditions. First, we estimate noise from each noisy speech frame using a speech presence probability (SPP) method to compute the noise variance. Then construct a whitening filter (with its coefficients computed from the estimated noise) and employed to the noisy speech, yielding a pre-whitened speech, from where the speech LPC parameters are computed. Then construct KF with the estimated parameters, where the robustness metric offsets the bias in Kalman gain during speech absence to that of the sensitivity metric during speech presence to achieve better noise reduction. Where the noise variance and the speech model parameters are adopted as a speech activity detector. The reduced-biased Kalman gain enables the KF to minimize the noise effect significantly, yielding the enhanced speech. Objective and subjective scores on NOIZEUS corpus demonstrates that the enhanced speech produced by the proposed method exhibits higher quality and intelligibility than some benchmark methods.

Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions

While nursing is an ethical profession, unethical behavior among nurses is increasing worldwide. This study examined the effects of an ethics seminar on nurses' moral sensitivity and ethical behavior. A total of 37 nurses (17 experimental, 20 control) were recruited. The ethics seminar was held over a 6-month period from May to October, 2018, and comprised six sessions held once a month for two hours. Moral sensitivity and unethical behavior were measured at the start and end of the seminar. Moral sensitivity and unethical behavior showed a negative correlation (r= -.455, p&lt;0.01). After the ethics seminar, the experimental group's moral sensitivity was significantly increased (t = -1.039, p = 0.314). The mean scores of unethical behavior at pre and post-test in the experimental group were 12.59 and 9.47, respectively. This was a statistically significant difference (t = 3.118, p = 0.004). There was no statistically significant difference in the mean score in both moral sensitivity and unethical behavior in the control group. We conclude that ethics seminars can enhance moral sensitivity and reduce the risk of unethical behavior among nurses. Regular ethics seminars and training must be provided to nurses as a matter of policy.

Most of the research of mental fatigue evaluation mainly concentrated on some indexes that require sophisticate and large instruments which make the detection of mental fatigue cumbersome, time-consuming, and difficult to apply on a large scale. A quick and sensitive mental fatigue detection index is necessary so that mental workers can be alerted in time and take corresponding countermeasures. But to date, no studies have compared the sensitivity of common objective evaluation indexes. To solve these problems this study recruited 56 human subjects. These subjects were evaluated using six fatigue indexes: the Stanford sleepiness scale, digital span, digital decoding, short-term memory, critical flicker fusion frequency (CFF), and speed perception deviation. The results of fatigue tests before and after mental fatigue were compared, and a one-way analysis of variance (ANOVA) was performed on the speed perception deviation. The result indicated the significance of this index. Considering individual differences, the relative fatigue index (RFI) was proposed to compare the sensitivity of the indexes. The results showed that when the self-rated fatigue grade changed from non-fatigue to mild fatigue, the ranges of RFI values for digital span, digital decoding, short-term memory and CFF were 0.175–0.258, 0.194–0.316, 0.068–0.139, and 0.055–0.075, respectively. Correspondingly, when the self-rated fatigue grade changed from non-fatigue to severe fatigue, the ranges of RFI values for the above indexes were 0.175–0.258, 0.194–0.316, 0.068–0.139, and 0.055–0.075, respectively. These results suggest that the sensitivity of the digital decoding, digital span, short-term memory, and CFF decreased sequentially when the self-evaluated fatigue grade changed from no fatigue to mild or severe fatigue. The RFI individuality of the speed perception deviation is highly variable and is not suitable as an evaluation index. In mental fatigue testing, digital decoding testing can provide faster, more convenient, and more accurate results.

It is unclear which noise exposure time window and noise characteristics during nighttime are most detrimental for sleep quality in real life settings. We have conducted a field study with 105 volunteers wearing a wrist actimeter to record their sleep during seven days, together with concurrent outdoor noise measurements at their bedroom window. Actimetry recorded sleep latency increased by 5.6 minutes (95% confidence interval: 1.6 to 9.6 minutes) per 10 dB(A) increase in noise exposure during the first hour after bedtime. Actimetry assessed sleep efficiency was significantly reduced by 2-3 percent per 10 dB(A) increase in measured outdoor noise (Leq, 1h) for the last three hours of sleep. For subjectively reported sleepiness, noise exposure during the last hour prior to wake up was most crucial with an increase in the sleepiness score of 0.31 units (95% CI: 0.08 to 0.54) per 10 dB(A) Leq,1h. Associations for estimated indoor noise were not more pronounced than for outdoor noise. Considering noise events in addition to equivalent sound pressure levels (Leq) only marginally improved the statistical models. Our study provides evidence that matching the nighttime noise exposure time window to the individual’s diurnal sleep-wake pattern results in a better estimate of detrimental nighttime noise effects on sleep. We found that noise exposure at the beginning and the end of the sleep is most crucial for sleep quality.

Cholera is an acute enteric infectious disease caused by the Gram-negative bacterium Vibrio Cholerae. Despite a huge body of research, the precise nature of its transmission dynamics has yet to be fully elucidated. Mathematical models can be useful to better understand how an infectious agent can spread and be properly controlled. We develop a compartmental model describing a Human population, a bacterial population as well as a phage population. We show that there might be eight equilibrium points; one of which is a disease free equilibrium point. We carry out numerical simulations and sensitivity analyses and we show that the presence of phage can reduce the number of infectious individuals. Moreover, we discuss the main implications in terms of public health management and control strategies.

Surrogate model based optimization method is widely-used to accelerate the design and optimization process~\cite{marler2004survey}. The input of regression model used in the surrogate model are numbers, which requires users to parametrize the geometries. In this paper, a new parameterization-free surrogate model is introduced and its corresponding uncertainty quantification and sensitivity analysis method are discussed. The input of new surrogate model methods is surface mesh of simulation domain. \Gls{gnns} is used to extract geometric information, and \Gls{cnns} is used to predict contours. This framework bypasses parameterization,as a consequence, uncertainties introduced by manual parameterization is reduced. However, such changes compared with conventional surrogate model methods impose great challenge on uncertainties quantification and sensitivity analysis. Uncertainties quantification in this paper means the error bar of prediction results, which is calculated by Gaussian Process Regression method in current surrogate method. In this paper, a new quantification method achieved by Kullback-Leibler divergence (KLD) is introduced. And the sensitivity analysis is conducted by Automatic Differentiation, which gives a Jacobian matrix of inputs. The method and analysis mentioned above are demonstrated by a low-pressure steam turbine rotator and its exhaust system.

Purpose: The accuracy of conventional visual function tests, which emit visible light, decreases in patients with corneal scars, cataracts, and vitreous hemorrhages. In contrast, infrared (IR) light exhibits greater tissue penetrance than visible light and is less susceptible to optical opacities. We therefore compared visual function results obtained using conventional visual function tests and infrared 2-photon microperimetry (2PM-IR) in a subject with a brunescent nuclear sclerotic and posterior subcapsular cataract before and after cataract surgery. Methods: Visual function testing using the cone contrast threshold (CCT) test, conventional microperimetry (cMP), visible light microperimetry from a novel device (2PM-Vis), and 2PM-IR were performed before and after cataract surgery. Results: Cone contrast threshold testing improved for the S-cone, M-cone, and L-cone by 111, 14, and 30. Retinal sensitivity assessed using cMP, 2PM-Vis, and 2PM-IR improved by 18 dB, 17.4 dB, and 3.4 dB, respectively. Conclusions and Importance: 2PM-IR, unlike conventional visual function tests, showed minimal variability in retinal sensitivity before and after surgery. Thus, IR visual stimulation introduces a paradigm shift for measuring visual function in the retina and posterior visual pathways by circumventing optical media opacities.

Flow and transport processes in soil and rock play a critical role in agricultural non-point source pollution (ANSP) loads. In this study, we investigated the ANPS load discharged into rivers from an irrigation district in the Tibetan Plateau, and simulated ANPS load using a distributed model involving detailed descriptions of flow and ANPS transport and transformation processes in the soil and rock. Experiments were conducted for two years to measure soil water content and nitrogen concentrations and the quality and quantity of lateral flow in the rock and at the drainage canal outlet during the highland barley growing period. A distributed model, in which the subsurface lateral flow was described using a step-wise method, was developed to simulate flow and ammonium nitrogen and nitrate nitrogen transport. Sobol’s method was used to evaluate the sensitivity of simulated flow and transport processes to model inputs. The results showed that, with a 21.2% increase of rainfall and irrigation in the highland barley growing period, the average NH4+-N and NO3--N concentrations in the soil layer decreased by 10.8% and 14.3%, respectively, due to increased deep seepage. Deep seepage of rainfall water accounted for 0–52.4% of total rainfall, whereas deep seepage of irrigation water accounted for 36.6–45.3% of total irrigation. NH4+-N and NO3--N discharged into the drainage channel represented 19.9–30.4% and 19.4–26.7% of the deep seepage, respectively. The mean Nash-Sutcliffe coefficients, root mean square errors, and cumulative deviations between the measured and simulated flow rates and NH4+-N and NO3--N concentrations at the surface drainage canal outlet were 0.694, 0.081, and 0.242, respectively, indicating that the proposed method can effectively describe the hydrological and ANPS pollution migration in the plateau irrigation zone. The Sobol’ sensitivity analysis results demonstrated that subsurface lateral flow had the most important first order and total effect on the simulated flow and NH4+-N and NO3--N concentrations at the surface drainage outlet.

Chemotherapy treatment based on Cisplatin (CDDP) is established as the drug of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironment alteration through a dynamic balance of mitochondrial fission and fusion. HNSCC is known to have hypoxic conditions, yet the effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain unclear. We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was shown to be correlated with chemosensitivity in clinical samples of HNSCC that underwent a hypoxic condition. Hypoxia-inducible factor 1 α-subunit (HIF-1α) dramatically increased Mff transcriptional expression and directly bound to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α, Mff expression, and mitochondrial fission. Moreover, a knockdown of Mff suppressed hypoxia-induced mitochondrial fission and decreased CDDP chemosensitivity in vivo and in vitro. Our findings revealed that the hypoxia-induced release of ROS promoted mitochondrial fission and CDDP chemosensitivity via the regulation of HIF-1α/Mff in HNSCC cells, indicating that Mff may serve as a new biomarker to predict neoadjuvant chemosensitivity in HNSCC patients

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as sub-Saharan Africa (SSA). The advent of coronavirus has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis (PRISMA). We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full-text via EBSCOhost databases from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to the gold reference standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458-0.541); 0.535 (95% CI: 0.401-0.663); 0.952 (95% CI: 0.60-1.324); 1.381 (95% CI: 0.391-4.879); and 0.944 (95% CI: 0.579-1.538), respectively. Evidence shows that mobile-linked POC diagnostics' diagnostic accuracy is presently moderate in detecting infections in sub-Saharan Africa. Future research is recommended to evaluate mHealth devices' diagnostics with excellent sensitivities and specificities in diagnosing diseases in this setting.

The modeling and prediction of crop seed yield can be a vital improvement in the precision agriculture industry as it provides reliable assessments of the effectiveness of agro-traits. Here, multiple machine learning (ML) techniques are established for predicting sesame (Sesamum indicum L.) seed yield (SSY) and incorporating agro-morphological features. Models utilized for coupled PCA-ML (Principal component analysis-Machine Learning) methods were compared with original ML models to evaluate predicted efficiency. The Gaussian process regression (GPR) and Radial basis function neural network (RBF-NN) models exhibited the most accurate SSY predictions with determination coefficients or R2 values of 0.99 and 0.91, respectively. The root-mean-square error (RMSE) for the ML models fluctuated between 0 to 0.30 t/ha (metric tons/hectare) for the varied modeling process phases. Estimation of sesame seed yield with coupled PCA-ML models improved performance accuracy. The K-fold process suggested the utilization of datasets with the lowest error rates to ensure the continued accuracy of GPR and RBF models. Sensitivity analysis revealed the capsule number per plant (CPP), seed number per capsule (SPC), and 1000-seed weight (TSW) were the most significant seed yield determinants.

Aim: To investigate the application of anterior and posterior corneal higher order aberrations (HOAs) in detecting keratoconus (KC) and suspect keratoconus (SKC). Method: This is a retrospective, case-control study which evaluated non-ectatic (normal) eyes, SKC eyes, and KC eyes. The Sirius Scheimpfug (CSO, Italy) analyzer was used to measure HOAs of the anterior and posterior corneal surfaces. Sensitivity, specificity and area under receiver operating characteristic curve (AUC) were calculated. Results: Two-hundred and twenty eyes were included in the analysis (normal n = 108, SKC n= 42, KC n= 70). Receiver operating characteristic (ROC) curve analysis revealed a high predictive ability for anterior corneal HOAs parameters: Root mean square (RMS) total corneal HOAs, RMS trefoil and RMS coma to detect keratoconus (AUC > 0.9 for all). RMS Coma (3, ±1) derived from the anterior corneal surface was the parameter with the highest ability to discriminate between suspect keratoconus and normal eyes (AUC = 0.922; cutoff > 0.2). All posterior corneal HOAs parameters were insufficient in discriminating between SKC and normal eyes (AUC < 0.8 for all). In contrast, their ability to detect KC was excellent with AUC of > 0.9 for all except RMS spherical aberrations (AUC = 0.846). Conclusion: Anterior and posterior corneal higher order aberrations can differentiate between keratoconus and normal eyes, with a high level of certainty. In suspect keratoconus disease however, only anterior corneal HOAs, and in particular coma-like aberrations, are of value. Corneal aberrometry may be of value in screening for keratoconus in populations with a high prevalence of the disease.

Early stroke diagnosis remains a big challenge in healthcare partly due to the lack of reliable diagnostic blood biomarkers, which in turn leads to increased rates of mortality and disability. Current screening methods are optimised to identify patients with a high risk of cardio-vascular disease, especially among the elderly. However, in young adults and children, these methods suffer low sensitivity and specificity and contribute to further delays in their triage and diagnosis. Accordingly, there is an urgent need to develop reliable blood biomarkers for triaging patients suspected of stroke in all age groups, especially children and young adults. This review explores some of the existing blood biomarkers, as single biomarkers, or biomarker panels, and examine their sensitivity and specificity for predicting stroke. A review was performed on PubMed and Web of Science for journal articles published in English during the period 2001 to 2021 which contained information regarding biomarkers of stroke. In this review article, we provide comparative information on the availability, clinical usefulness, and time-window periods of eight single blood biomarkers and six biomarker panels that have been used for predicting stroke in emergency situations. The outcomes of this review can be used in future research for developing more effective stroke biomarkers.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

The effects of transcranial magnetic stimulations (TMS) show that the human brain is impacted by some magnetic fields (EMFs). Moreover, after a delay, it produces potentials that reveal a subsequent processing of this impact. The human brain might also be sensitive to very weak magnetic fields of extremely low frequencies (vwEMFelf). Namely, to the vwEMelf produced by the brain of other persons when they process visual stimuli. In effect, two studies report that the event-related brain potentials (ERPs) that are evoked by presenting a picture to a participant can be modulated by simultaneously presenting a picture to a partner. To confirm it here, we followed most of the methods of these studies. We recorded the ERPs evoked by presenting, at each trial, the photograph of a face. Simultaneously and, most importantly, privately, we presented a partner with the same or with a different face photograph. ERPs of participants were found to depend on that sameness (p0.001), unbeknownst to them. These joint processing effects (JPEs), confirm a sensitivity of the human brain to the vwEMFelf produced by other brains.

The current systematic review examines whether there is an association between the genetic 5-HTTPLR pol-ymorphism and parenting and the mechanisms by which this association operates. The literature was searched in various databases such as PubMed, Scopus and ScienceDirect. In line with our inclusion criteria, nine articles were eligible out of 22. Most of the studies, analysed in this review, found an association between 5HTTLPR and parenting. Four studies found a direct association between 5-HTTLPR and parenting with conflicting findings: two studies found that mothers carrying the short variant were more sensitive to their infants, while two studies found that parents carrying the S allele were less sensitive. In addition, several studies found strong interaction between genetic and environmental factors, such as childhood stress and disruptive child behaviour, quality of early care experiences, poor parenting environment, and quality of environment. Only one study found an association between children’s 5HTTLPR and parenting. Parenting can be described as a highly complex construct influenced by multiple factors, including environmental, parenting and child charac-teristics. According to the studies, maternal 5-HTTLPR polymorphism is most likely associated with sensitive parenting.

Using nanoindentation under various strain rates, the mechanical properties of a selective laser melted (SLM) SKD61 at the 800 mm/s scan speed was investigated and compared to SLM H13. No obvious pile-up due to the ratio of the residual depth (h_f) and the maximum depth (h_max) being lower than 0.7 and no cracking were observed on any of the indenter surfaces. The nanoindentation strain-rate sensitivity (m) of SLM SKD61 was found to be 0.034, with hardness increasing from 8.65 GPa to 9.93 GPa as the strain rate increased between 0.002 s⁻¹ and 0.1 s⁻¹. At the same scan speed, the m value of SLM H13 (m = 0.028) was lower than that of SLM SKD61, indicating that the mechanical behavior of SLM SKD61 was more critically affected by the strain rate compared to SLM H13. SLM processing for SKD61therefore shows higher potential for advanced tool design than for H13.

While the link between Sensory-processing sensitivity (SPS) and internalizing symptoms has been well-established, a link to externalizing problems is still to be explored. This study aimed to further examine the relation between SPS and behavioral problems by testing the potential mediating roles of trait emotional intelligence (TEI) and decision-making styles. Pathway analyses were conducted on data from 268 community sample participants (Mage= 25.81, SD=2.41, 61.2% females). Results indicated gender differences in the pathway level outcomes of SPS, as well as potential partial mediators in men and women. SPS both directly and via the mediating effects of well-being factor (TEI) and avoidant decision-making influenced depression, regardless of gender. Direct effects on aggression were, however, obtained only in the male sample. Indirect effects of SPS on aggression were found in spontaneous decision-making for men, and in self-control and sociability factors of TEI for women. Directions for future research were discussed. sensory-processing sensitivity, depression, aggression, emotional intelligence, decision-making style, gender differences