Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

In order to reduce the silique shattering loss of rapeseed mechanical harvesting process, based on the state of force on the silique during rapeseed harvesting reel branch, Ningza 1810, Zhenyou 8 and Fengyou 306 were used as research objects, and the experimental research on the factors affecting rapeseed siliques shattering was carried out using the swing impact method. The experimental analysis showed that: rapeseed varieties, silique moisture content, silique growth position, collision material, impact speed, force position and other factors had significant effects on silique shattering. The impact velocity was less than 1.5m·s-1, the difference on the effect of each factor on pod-shattering was not significant, it was not easy to shatter when the moisture content of rapeseed silique was higher. The impact resistance of the front side of rapeseed was 2 to 4 times that of the bonding surface of rapeseed petals, the shattering rate of the top rapeseed silique was twice that of the bottom siliques, when siliques were supported, they were more likely to shatter under external forces than when they were unsupported. The experimental study of the mechanical properties of rapeseed siliques was carried out using the impending fracture method, the experimental analyses showed that the support position and force position of the silique, the loading speed and the growth position of the silique had a significant effect on the mechanical properties of the silique. The maximum cracking force was higher and bending strength was stronger when the body of the silique was supported, which the range of the maximum cracking force were 3.05N to 4.16N, and the bending strength range were 8.48 MPa to 11.57 MPa. The maximum cracking force and bending strength of the silique was stronger when the front side of the silique petal was pressurized than when the bonding surface of the petal was pressurized. Based on Pearson's correlation and grey correlation analysis, the morphological characteristics of rapeseed siliques were ranked in order of their influence on the performance of siliques in terms of the angle between silique and stalk, stalk diameter, petal thickness, beak length, silique thickness, silique width and silique length. This study can be used as a reference for the design and optimization of the rapeseed harvesting reel branch mechanism and the selection of machine harvestable rapeseed varieties.

Event-related potentials (ERPs) are estimated by averaging time-locked single trial electroencephalography (EEG) signals in response to specific events or stimuli. Classifying ERPs accurately is a challenge because (a) single trials have poor signal-to-noise-ratios (SNRs) and (b) it is difficult to collect large single trial ensembles to generate high SNR ERPs for classifier training and testing. The m-subsample averaging (m-SA) strategy which generates small-sample ERPs by repeated averaging of a small number of single trials drawn without replacement, has been proposed as a solution to the two problems. An ERP formed by averaging m single trials is referred to as an m-ERP where m is referred to as the averaging parameter. In this study, we conduct thorough analyses of m-SA and focus on issues not addressed in previous studies to better understand the beneficial properties of m-SA and to further support its application for ERP classification. Specifically, we (a) analyze the improvement in SNR as a function of m using the mean-root-mean-square SNR and visual analyses of m-ERP plots with confidence intervals, (b) analyze the improvement in interclass separation as a function of m, (c) determine how the SNR and interclass separation analyses can help to select the averaging parameter m, (d) determine the number of distinct m-ERPs that can be drawn from a single-trial ensemble, and (e) determine several probabilities related to the generation of distinct m-ERPs. Furthermore, an extensive set of experiments are designed to analyze the performance of support vector machine and convolution neural network classifiers employing m-SA with various combinations of the averaging parameters used for generating the training and test sets. The results confirm that ERPs can be classified accurately using small subsample averaging. Most importantly, it is concluded that m-SA can be deployed in practice to accurately classify ERPs in brain activity research and in clinical applications without having to collect a prohibitively large number of single trials.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.

Appetitive traits have been associated with eating behaviors and weight in youth. However, the relationships among adults have received less attention. In this study, we measured appetitive traits among 520 female college students from a University in eastern Chinese using the Chinese translated Adults Eating Behavior Questionnaire (C-AEBQ) and found that two food approach traits (food enjoyment and emotional over-eating) were positively while two food avoidance traits (slowness in eating and satiety responsiveness) were negatively associated with BMI. Individual trait was differentially associated with eating behaviors. Specifically, a positive correlation was found between food responsiveness and higher frequency of selecting delivery food, spicy food, and sugared beverage; conversely, satiety responsiveness was associated with higher frequency of skipping meals. Using latent profile analysis, participants were classified into four appetitive patterns: food approacher, food approacher with emotional under-eating, food avoider, and food avoider with emotional over-eating. Food avoiders had significant lower BMI and higher proportion of underweight than other three patterns. Compared to food approacher, food avoiders had higher frequency of skipping breakfast, and food avoiders with emotional over-eating had higher frequency of skipping both breakfast and lunch. No significant differences were observed in food choice and dieting behavior among four appetitive patterns. The findings suggested a correlation between an individual’s appetitive pattern and eating behaviors among female college students, those with food avoidance patterns are more likely to have irregular meals, which may contribute to their low BMI. The findings provide valuable insights for female college students to cultivate a healthy eating behavior and sustain a healthy body weight.

State legitimacy and effectiveness could be seen by the way to deliver welfare to citizens to mitigate social grievances, that could eventually lead to conflicts (Kivimäki, 2021). Social security systems in Maghreb countries are quite similar in their architecture and aims to provide social insurance to all the workers in the labor market. However, they suffer from the same main problem: the low rate of enrollment of workers. Many workers (employees and self-employed) work informally without any social security coverage. The issue of whether informal jobs are chosen voluntarily by workers or as a strategy of last resort is controversial. Many authors recognize that the informal sector is heterogeneous and it is made up of workers who voluntary choose it and others who are pushed inside because of entry barriers to the formal sector (Günther & Launov, 2012). Using the SAHWA survey and discrete choice models, this article confirms the heterogeneity of the informal labor market in three Maghreb countries: Algeria, Morocco, and Tunisia. Furthermore, this article highlights the profiles of workers who voluntarily choose informality, which is missing from previous studies. Finally, this article proposes policy recommendations in order to extend social security to informal workers and to include them in the formal labour market.

The framework of product life cycle (PLC) cost analysis is one of the most important evaluation tools for a contemporary high-tech company in an increasingly competitive market environment. The PLC-purchasing strategy provides the framework for a procurement plan and examines the sourcing strategy of a firm. The marketing literature emphasizes that ongoing technological change and shortened life cycles are important elements in commercial organizations. From a strategic viewpoint, the vendor has an important position between supplier, buyer and manufacturer. The buyer seeks to procure the products from a set of vendors to take advantage of economies of scale and to exploit opportunities for strategic relationships. However, previous studies have seldom considered vendor selection (VS) based on PLC cost (VSPLCC) analysis. The purpose of this paper is to solve the VSPLCC problems considering the situation of a single-buyer-multiple-supplier. For this issue, a new VSPLCC procurement model and solution procedure are derived by this paper to minimize net cost, rejection rate, late delivery and PLC cost subject to vendor capacities and budget constraints. Moreover, a real case in Taiwan is provided to show how to solve the VSPLCC procurement problem.

Efficient use of agricultural wastes and by-products, basically transforming waste materials into value added products, is considered as pivotal for an effective bioeconomy strategy for the rural development. To this scope, citrus waste management represents a major issue for citrus processors but, at the same time, it embodies a potentially unexploited resource for the rural sustainable development. This study focuses on analyzing the current management of citrus waste in South Italy and identifying the determinants and barriers that may affect an entrepreneur’s choice on the destination of citrus waste. Citrus processors’ preferences about the contract characteristics needed to take part in a co-investment scheme have been investigated. Both analyses are preliminary steps to design an innovative and sustainable citrus by-product supply chain. Results show that the distance between the citrus processors and the citrus by-products plant is one of the main criteria for choosing alternative valorization pathways. Moreover, the required guaranteed capital, the short duration of the contract, and low risk are contract scheme characteristics that improve entrepreneurs’ willingness to co-invest in the development of a citrus waste multifunctional plant.

Efficient commencement of clinical trials is pivotal for their successful execution. The purpose of this study was to determine and examine the factors that contribute to trial start-up delays. The study assessed 20 clinical trials' start-up stages in order to identify relevant variables. Results showed that trials with an emphasis on devices, trials that did not outsource, trials that utilized less auxiliary services, and trials that employed interventional designs had quicker start-up times than observational studies. Furthermore, approval times were substantially shortened by using a centralized Institutional Review Board (IRB) rather than a local IRB. Furthermore, compared to studies that successfully enrolled subjects, those who failed to do so required more time to complete contracts and budgets and secure IRB clearance. This study underscores the diverse impact of clinical trial features on start-up timelines. Understanding these factors is crucial for optimizing the initiation process of clinical trials.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

This study evaluated the effect of low-level laser irradiation induces by diode laser on the speed of orthodontic tooth movement of canines submitted to initial retraction. Twenty-four mandibular canines were retracted by using NiTi spring (force of 150 g/side). Thirteen of those were irradiated with a diode laser 980-nm diode laser (Wiser Laser Doctor Smile, Lambda) operating at an 810-nm wavelength (1 W of output power, continuous wave of 66.7 J/cm2) that was equipped with a 0.6-mm optical fiber in continuous-wave mode. The canine retraction was accomplished by using prefabricated coil springs. The right of the mandible was chosen to be irradiated with the laser, whereas the left side was considered the control without laser irradiation. The laser was applied with 0-, 3-, 7-, and 14-day intervals. The amount of canine retraction was measured with a digital electronic caliper while the pain level was prompted by a patient questionnaire. The speed of tooth movement was significantly greater in the laser group than in the control group. The pain intensity was also at a lower level in the laser group. Our findings suggest that diode laser therapy can highly accelerate tooth movement during orthodontic treatment and can also effectively reduce pain level.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

Diet-related diseases impact populations across the globe. While intertemporal preferences—a fundamental preference for the distribution of benefits across time—have been used to explain low-quality food choices, recent literature proposes another cause: inattention to future implications (or opportunity costs) of the options faced. Food choices tend to become habitual to conserve cognitive resources, rather than carefully modeling future health impacts. Both low discount rates for future benefits and attention to future health impacts predict healthier decisions. While intertemporal preferences are stable, attention may provide an opportunity to intervene in the decision process to promote healthier decisions. In this study, we test the impact of a simple message that highlights health during food choice on the healthiness of foods chosen and on health consideration and intertemporal preferences. Our results show that actively considering health outcomes and lower discount rates lead to healthier food choices. We find that messaging increases the consideration of health outcomes during food choice but does not affect intertemporal preferences, suggesting that simple prompts may be an effective way to promote decisions balancing short and long-term benefits by drawing attention to overlooked opportunity costs of choices.

Particles and photons appear to be total opposites; the former has rest mass which requires space to exist; the latter has kinetic energy which requires time to occur (oscillate). But they do share certain properties (e.g., quantization) that remain invariant when one is transformed (swapped) for the other. This gauge invariance is developed in some detail.The symmetry between particle and photon turns out to be one of inversion. It is the equalities of special relativity that support this inversion and the accompanying invariances: mass transformed to energy; space transformed to time. The great advantage of these symmetries (inversions) is that they provide guidance for an object little understood (the photon) based upon an object well understood (the particle). On this basis, progress can be made in the understanding of some long-standing issues: wave-particle duality, time’s arrow, the constant speed of light and nonlocality.

Open domain question answering (OpenQA) tasks have been recently attracting more and more attention from the natural language processing (NLP) community. In this work, we present the first free-form multiple-choice OpenQA dataset for solving medical problems, MedQA, collected from the professional medical board exams. It covers three languages: English, simplified Chinese, and traditional Chinese, and contains 12,723, 34,251, and 14,123 questions for the three languages, respectively. We implement both rule-based and popular neural methods by sequentially combining a document retriever and a machine comprehension model. Through experiments, we find that even the current best method can only achieve 36.7%, 42.0%, and 70.1% of test accuracy on the English, traditional Chinese, and simplified Chinese questions, respectively. We expect MedQA to present great challenges to existing OpenQA systems and hope that it can serve as a platform to promote much stronger OpenQA models from the NLP community in the future.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

FMD is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are used to induce an immune response, but it is not sufficient to show the effect of preventing viral infection. In this study, we conducted to evaluate the increasing effect of FMD vaccine SP antibody by administrating Zn-ASP to 100 pigs from three test pig farms with feed. FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of FMD vaccine SP antibody in the 0.2% Zn-ASP-administered group significantly increased compared to that in the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8 and 16 weeks after the second vaccination, respectively (p<0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. IFN-γ and IgA were significantly increased by Zn-ASP administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p<0.05). On the other hand, serum AST, and CPK (p<0.001) were significantly decreased by Zn-ASP. Our results show that the administration of Zn-ASP is effective in enhancing the antibody titer and immunity of the FMD vaccine by FMD vaccination, and it is thought that it can be used as an oral adjuvant (OrAd) to prevent viral diseases such as FMD.

The purpose of the study was to investigate the bacterial viability of the initial biofilm on the surface of experimental modified dental resin composites. Twenty-five healthy individuals with good oral hygiene were included in this study. In a split-mouth design, they received acrylic splints with five experimental composite resin specimens. Four of them were modified with either a novel polymeric hollow beads delivery system or methacrylated polymerizable Irgasan (Antibacterial B), while one specimen served as unmodified control (ST). The delivery system based on Poly-Pore® was loaded with one of the active agents Tego® Protect 5000 (Antiadhesive A), Dimethicone (Antiadhesive B) or Irgasan (Antibacterial A). All study subjects refrained from toothbrushing during the study period. Specimens were detached from the splints after 8h and given a live/dead staining before fluorescence microscopy. Friedman test and post-hoc Nemenyi test were applied with significance level at p < 0.05. In summary all materials but Antibacterial B showed a significant antibacterial effect compared to ST. In conclusion dental resin composites with Poly-Pore loaded active agents show antibacterial effectiveness in situ.

Some of the European countries affected by COVID-19 have not learned from previous experience in China. Italy did not learn from China and Spain did neither learn from China nor from Italy. Confinement in Spain was postponed due to pressure from economic interests and traveling of infected people, especially from Madrid to the beaches in South-East Spain, was allowed. Strict confinement and border closure came late, when the curve of infected people and the death toll already had the worse trend worldwide. Tests to SARS-CoV-2 RNA detection by PCR, were first unavailable and, later, faulty and/or detecting antibodies and not the virus itself. Instead of mobilizing research laboratories for making tests, and instead of making masks and ventilators, mediatic scientists asked for money for controversial clinical trials and for obtaining a vaccine. In this scenario, common sense indicates that ad hoc measures should be taken at the end of confinement in order to minimize pain. The chain of errors should be avoided in the management of next pandemics by designing Good Practice Rules (GPRs). In addition, post-confinement measures should be implemented as soon as possible to be ready for SARS-CoV-2 return next season. In this sense a longitudinal study in the most affected cities (Madrid, Barcelona, Vitoria and Pamplona) should be performed with the primary objective of detecting carriers with no symptoms, to stratify patients according to symptoms, and to early detection of virus reappearance. Also relevant is to sequence as many viruses as possible to detect possible variants; there are still patients that are PCR positive.

E-scooters are a micromobility transportation option for completing short trips. In recent years, many ‎cities welcomed shared e-scooters in an effort to offer more mode choices, increase travelers' ‎convenience, and reduce automobile use in their service areas. However, a knowledge gap still remains ‎regarding the acceptability of shared e-scooters as a transportation option, which motivates additional ‎research on user and non-user preferences and attitudes toward e-scooter use. This study investigates ‎latent variables impacting the adoption of shared e-scooters in urban areas, focusing on mode choice ‎factors and attitudes towards e-scooter use and car use. The study utilizes machine learning (ML) ‎techniques and SHAP analysis to analyze survey data (N=1196) collected from travelers in Washington, ‎D.C., Miami, FL, and Los Angeles, CA, in 2021 and 2022. A comparative analysis is performed to develop ‎comprehensive demographic profiles of e-scooter users. The analysis reveals gender (male), age (25-39 ‎years age group), higher income, and educational background as the most relevant factors toward e-‎scooter use. Attitudinal variations among e-scooter users and non-users underscore the complexity of ‎perceptions toward e-scooter use, with significant differences in mode choice factors and attitudes ‎toward the use of e-scooters and private vehicles. Notably, educational background ranked as a significant ‎factor in Washington, D.C., and Miami, while Factor 3, derived from factor analysis and encompassing car ‎use attitudes and the utilization of technology, emerged as influential in Los Angeles. This research ‎contributes fresh insights into factors shaping e-scooter adoption, offering a foundation for informed ‎urban transportation planning and policymaking. The holistic approach showcased in this study enhances ‎understanding of shared micromobility and its implications for urban mobility.

Considering the aging society and budget constraints, a strategy for reforming public transportation welfare policies is essential for sustainability. Among the various transportation welfare policies, fare discount policies are provided to specific age groups, and most countries offer benefits to several public transportation. South Korea provides a fare-free policy limited to subways, and the need for policy modification is emerging due to sustainability problems caused by an aging society. Hence, the scope of the policy should be expanded to all travel modes, but the discount rate should be reduced, or the target group should be reduced in consideration of the budget. This study proposes a travel mode to focus on by city through the preference of the elderly. The latent class model is employed to classfy stated preference data collected from the survey. The estimation results show a significant preference heterogeneity depending on the level of subway supply by region, and a policy focused on subways would be more reasonable in cities with sufficient subway infrastructure. Hence, regarding sustainability, it may be more appropriate to focus on specific means than to provide the same discount policy for all public transport.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards a more and urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life-cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted in Austria. Individual partworth utilities were estimated by means of Hierarchical Bayes. Results show higher WTP for a positive evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negative evaluated multi-level label showed higher WTP compared to no label, pointing towards limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preferences for animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging and sustainability labels have only a small impact on the meat product choice of average consumers.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

This paper examines the importance of choice of cooking fuels in wellbeing, analysing relationships between the proportion of population with primary reliance on different types of fuels for cooking (predictor variable), and key wellbeing indices (outcome variables) - Personal Health, Social Life, Civic Engagement, Life Evaluation, Negative Experience. By combining two global datasets from Gallup and WHO, the study adds to current evidence by taking a global perspective. Controlling for demographic factors such as income per capita, age, education level, employment, etc., regression modelling of these relationships show that clean cooking fuels are influential in all of the key wellbeing indices with the exception of the Life Evaluation Index. Among the key wellbeing indices, Personal Health and Negative Experience Indices are the most strongly influenced by choice of clean cooking fuels. By adding access to electricity as an additional predictor variable, the analysis highlights the potential for integrating eCooking into national electrification plans as part of sustainable energy transitions, given that health outcomes (Personal health and Negative experience indices) appear to be as closely linked to choice of cooking fuels as to access to electricity.

Suppose for n∈ ℕ, set A⊆ℝⁿ and function f∶A→ℝⁿ. If set A, using the Hausdorff outer measure, is measurable in the sense of Carathèodory; we want to find an extension of the expected value, w.r.t the Hausdorff measure, that's unique, finite and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. The issue is current extensions of the expected value are finite for all functions in only a shy subset of ℝᴬ. The reason this issue wasn't resolved is mathematicians have not thought of the problem, focusing on application rather than generalization. Despite the lack of potential use, we'll attempt to solve the problem by defining a choice function---this shall choose a unique set of equivalent sequences of sets (Fₖ***) , where the set-theoretic limit of Fₖ*** is the graph of f; the measure Hʰ is the ℎ-Hausdorff measure, such for each k∈ℕ, 0 < Hʰ(Fₖ***) < +∞; and (fₖ*) is a sequence of functions where {(x,fₖ*(x))∶x∈ dom(Fₖ***)}=Fₖ***. Thus, the extended expected value of or E**[f,Fₖ***] is: ∀(ε>0)∃(N∈ℕ)∀(k∈N)(k≥N⇒1/Hʰ(dom(Fₖ***))∫dom(Fₖ*** )fₖ* dHʰ - E**[f,Fₖ***]<ε ) which should be unique, finite, and "natural" (defined on §2.3 & §2.4) for all f in a prevalent subset of ℝᴬ. Note we guessed the choice function using computer programming but we don’t use mathematical proofs due to the lack of expertise in the subject matter. Despite this, the biggest use of this research is the extension of the expected value is finite for "almost all" functions: this is easier to use in application when finding the "average" of functions covering an infinite expanse of space.

Types of DNA recombination include homologous recombination and nonhomologous recombination. Homologous DNA recombination is a general term that includes exchange of information between chromatids: (reciprocal) crossing-over, gene conversion, and post-meiotic segregation. Gene conversion is now thought to be a type of non-Mendelian segregation of heterozygous markers near the recombination initiation site. Thus, it includes both gene conversion and post-meiotic segregation previously described. DNA non-HR including transpositional recombination and site-specific recombination. Our understanding of the molecular mechanism by which DNA recombination occurs has significantly increased in the past decades. Currently The synthesis-dependent strand annealing model is now thought to give rise to most or all noncrossovers, with the double-strand-break repair model forming mainly crossovers. The Shapiro model proposed by Dr. J. Shapiro explains the molecular mechanism of transpositional recombination. Site-specific recombination results from another distinct model. We previously proposed a novel theory which can provide a more reasonable and simpler explanation accounting for DNA HR including the 3 classes of recombinogenic events described above. In the new supplementedly molecular model, DNA meiotic recombination can be initiated by a copy choice mechanism, that is, copying part of 1 single-stranded DNA template, followed by DNA polymerase switching to another single-stranded DNA template, and then resuming the following DNA synthesis along the new template. The current review suggests that transpositional recombination and site-specific recombination should be initiated by copy choice during DNA synthesis rather than break/join mechanism. The work indicates that review of DNA nonhomologous recombination are very necessary. The novel theory would challenge earlier models accounting for transpositional recombination and site-specific recombination and would be critical to the understanding of the mechanisms. We hope copy choice initiating DNA nonhomologous recombination will be one of the concepts that are explored. Proper and specific experiments are required to reconstruct the detailed mechanism described here.

Abstract Background: Cluster randomized controlled trials are increasingly becoming popular in public health research interventions and health services research in primary health care design and use in low and middle-income countries. However, the majority of researchers in these trials did not account correctly for the effect of confounders and clustering in the design and analysis stages. Objectives: This article aimed to review the main implications of implementing a cluster randomized controlled trials design in public health research and emphasize the practical application of proper analytical methods and the performance of different statistical models. Methods: The practical application of various analytical methods is validated via the utilization of experimental data from a public health research case study. This article also demonstrated the performance of hierarchical models and made comparisons in terms of empirically precise effect size estimates. Results: Three hierarchical statistical models were provided with highly varied effect sizes during the analysis of the intervention effect on outcome, such as model 1 (AOR: 14.32; 95% CI: 3.75–54.68), model 2 (ARR: 3.52; 95% CI: 2.16–5.77), and model 3 (ARR: 4.79; 95% CI: 2.69–5.52).Conclusion: Inaccurate results and potentially misleading conclusions can arise from improper cluster randomized controlled trial designs and analyses. This article has shown that real-world data can be adjusted for the effects of confounders and clustering, and we advocate for the routine use of suitable design and analytical methods. This article concludes that researchers should be careful when selecting hierarchical models to analyze cluster randomized controlled trials.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Background and aim. The study aimed to assess the efficacy of the treatment of Kan Jang®, a fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim in patients with mild symptoms of COVID-19. Methods. One hundred forty patients received six capsules of Kan Jang® (n = 68, daily dose of andrographolides – 90 mg) or placebo (n=72) and supportive treatment (paracetamol) for 14 consecutive days in a randomized, quadruple-blinded, placebo-controlled, two-parallel-group design. The efficacy outcomes were the rate of cases turning to severe, the detection rate of SARS-CoV-2 virus over the time of treatment, the duration and the severity of symptoms (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles) in the acute phase of the disease. Other efficacy measures included improving cognitive and physical performance, quality of life, and the levels of inflammatory blood markers - IL-6, c-reactive protein, and D-dimer. Results. Kan Jang® significantly (p < 0.05) reduced the rate of cases turning to severe (5.36%) compared to placebo (17.86%) and decreased the detection rate of SARS-CoV-2 virus over the time of treatment. The statistical difference in the rates of patients with clinical deterioration in the Kan Jang treatment and placebo control groups was significant (p = 0.0176) both in 112 patients included per protocol (IPP) analysis and in 140 patients included per intention to treat (ITT) analysis (p = 0.0236); the absolute risk reduction of cases by Kan Jang treatment was 12.5%, and the number Needed to Treat by Kan Jang was 8. The patient's recovery time (Number of sick days at the home/clinic) was shorter in the Kan Jang group compared with the placebo group. The rate of resolution of inflammatory symptoms in the Kan Jang® group was significantly higher compared with the placebo group, and relief of the severity of cough, sore throat/pain, runny nose, and muscle soreness. Kan Jang® significantly decreased the Wisconsin Upper Respiratory Symptoms scores compared to placebo in the sample size of 140 patients. However, the relief of fatigue and headache and the decrease of IL-6 in the blood was observed only in a subset of the 86 patients infected during the second three waves of the pandemic. Kan Jang® significantly increased physical activity and workout; however, it did not affect cognitive functions (attention and memory), Quality of life Score, inflammatory markers D-dimer, and c-reactive protein compared with the placebo group. Conclusions. Overall, the results of this study suggest that Kan Jang® is effective in treating mild and moderate COVID-19 irrespective of SARS-Cov-2 variants infection.

Cancer survival continues to improve in high-income countries, partly explained by advances in screening and treatment. Previous studies have mainly examined the relationship between individual dietary components and cancer prognosis in tumours with good therapeutic response (breast, colon and prostate cancers). The aim of this review was to assess qualitatively (and quantitatively where appropriate) the associations of dietary patterns and cancer prognosis from published prospective cohort studies, as well as the effect of diet interventions by means of randomized controlled trials (RCT). A systematic search was conducted in PubMed, and a total of 35 prospective cohort studies and 14 RCT published between 2011 and 2021 were selected. Better overall diet quality was associated with improved survival among breast and colorectal cancer survivors; adherence to the Mediterranean diet was associated to lower risk of mortality in colorectal and prostate cancer survivors. A meta-analysis using a random-effects model showed that higher versus lower diet quality was associated with a 23% reduction in overall mortality in breast cancer survivors. There was evidence that dietary interventions, generally combined with physical activity, improved overall quality of life, though most studies were in breast cancer survivors. Further cohort and intervention studies in other cancers are needed to make more specific recommendations.

This study focused on the characterization of lactic acid bacteria (LAB) in a renowned traditional Italian cheese, Pecorino di Farindola, to select an autochthonous culture and investigate its po-tential for the improvement of safety and functional properties. Two hundred and six LAB isolated throughout production and maturation from nine cheese lots of three farms were identified by 16S rRNA gene sequencing and tested for the presence of genes encoding virulence factors, vancomycin resistance (for enterococci), biogenic amines (BAs) and bacteriocin production, for antimicrobial activity, and for the capacity to survive in the gastro-intestinal tract (GIT) based on tolerance to low pH and bile salts and adhesion to CaCo-2 cells. A Lacticaseibacillus paracasei isolate was used in cheese making and determined a decline of spiked Listeria monocytogenes and Escherichia coli O157 faster than in control cheese. The autochthonous bacterial groups were numerically unaffected, apart from lactobacilli that were recovered in higher numbers in the cheese with added L. paracasei. Based on Repetitive Extragenic Palyndrome (Rep) PCR profiles, the added strain possibly dominated until day 88 in cheese. Results encourage further trials with autochthonous cultures to efficiently inhibit hazardous bacteria and enrich a functional microbiota in Pecorino di Farindola and similar cheeses.

A face serum composed of a combination of biologically active compounds was evaluated for safety and efficacy in vitro, in a repeat insult patch test and in a human clinical efficacy trial. The serum inhibited tyrosinase activity modestly, decreased collagenase activity and exhibited notable free radical scavenging activity in vitro. It is gentle to the skin, as the serum did not irritate the skin or produce symptoms of allergic contact dermatitis in the 55 healthy adults that participated in the repeat insult patch test. In the efficacy trial, daily application of the face serum for 30 days significantly increased skin hydration, with all 35 volunteers experiencing improvement. Substantial improvements in skin elasticity, roughness (fine lines and wrinkles), and brightness also occurred during the trial. Dermatological examination also revealed a trend for reduced comedone count with use of the serum. Self-assessment responses revealed that all volunteers experienced improvements in multiple skin quality parameters and that participant perceptions are consistent with the results of the instrumental analyses. These findings indicated that the measured improvements in skin quality are not only statistically significant but are also clinically relevant as they were great enough for users of the face serum to feel and recognize.

In India, where the transport sector contributes significantly to CO2 emissions, there has been a growing shift towards electric vehicles (EVs), particularly in the three-wheeler segment. Traditional auto-rickshaws, a staple in urban transportation, are often powered by internal combustion engines, leading to pollution and high fuel consumption. Electric three-wheelers, or e-rickshaws, have emerged as a cleaner, more efficient alternative, with zero tailpipe emissions. However, the successful adoption of electric three-wheelers depends on understanding the preferences and challenges faced by auto-rickshaw drivers, who are key to the Intermediate Public Transport (IPT) system. Based on this motivation, the study contributed to the literature by analyzing stated preference survey data from 2,403 respondents who purchased electric tricycles in 2023. We provide insights into the relationship between consumer demographics (such as age, income, gender, education), Vehicle operations, Vehicle financing and Electrification perspective and their preferences for specific electric and fuel tricycle segments. Finally, we estimate consumers' preference for electric tricycles and fuel tricycles. To do this, we use a discrete choice model and estimate the impact factor of Indian consumers in purchasing electric tricycles to obtain market penetration strategies for future electric tricycles.

In this work, optimal consumption and investment strategies are derived for risk-averse investors under the 4/2 stochastic volatility class of models. We work under an expected utility (EUT) framework and consider a Constant Relative Risk Aversion (CRRA) investor, who might also be ambiguity-averse. The corresponding Hamilton-Jacobi-Bellman (HJB) and HJB-Isaacs (HJBI) equations are solved in closed-form for a subset of the parametric space and under some restrictions on the portfolio setting, for complete markets. Conditions for proper changes of measure and well defined solutions are provided. These are the first analytical solutions for the 4/2 stochastic volatility model and the embedded 3/2 model for the type of excess returns established in .

In this paper, we will extend the expected value of the function w.r.t the uniform probability measure on sets measurable in the Caratheodory sense to be finite for a larger class of functions, since the set of all measurable functions with infinite or undefined expected values forms a prevalent subset of the set of all measurable functions, which means "almost all" measurable functions have infinite or undefined expected values. Before we define the specific problem in section 2, we will outline some preliminary definitions. We'll then define the specific problem (along with a partial solution in section 3) to visualize the complete solution. Along the way, we will ask a series of questions to clarify our understanding of the paper.

Food consumption in Europe is changing. Red meat consumption has been steadily decreasing in the past decades. The rising interest of consumers for healthier and more sustainable meat products provide red meat producers with the opportunity to differentiate their offers by ecolabels, origin and health claims. This international study analyses the European consumer preferences for red meat (beef, lamb and goat) in seven countries: Finland, France, Greece, Italy, Spain, Turkey and the United Kingdom. Through a choice experiment, 2.900 responses were collected. Mixed multinomial logit models were estimated to identify heterogeneous preferences among consumers at the country level. Results indicate substantial differences between the most relevant attributes for the average consumers, as well as their willingness to pay for them in each country. Nevertheless, national origin and organic labels were highly valued in most countries.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs) have been utilised to forecast the foreign exchange market (Forex). However, such models usually exhibit unstable behaviour, as data perturbations often downgrade the functionality of the entire network due to their monolithic architecture. Hence, this study proposes a novel neuroscience-informed modular network applied to the closing prices and the sentiments retrieved from Yahoo Finance and Twitter APIs, aiming to anticipate better price fluctuations in Euro to British Pound Sterling (EUR/GBP) rather than monolithic methods. The proposed model is based on a new modular CNN, replacing pooling layers with orthogonal kernel initialisation RNNs coupled with Monte Carlo Dropout (MCD), namely MCoRNNMCD. It combines two modules: i) a convolutional simple RNN and ii) a convolutional Gated Recurrent Unit (GRU), where orthogonality and MCD are added to reduce the overfitting, assessing each module's uncertainty. These parallel feature extraction modules concatenate their outputs to a final three-layer Artificial Neural Network (ANN) decision-making module. A comprehensive comparison viewing objective evaluation metrics such as the Mean Square Error (MSE) proved that the proposed MCoRNNMCD-ANN outperformed single CNN, LSTM, GRU, and the state-of-the-art hybrid BiCuDNNLSTM, CLSTM, CNN-LSTM, and LSTM-GRU in forecasting hourly EUR/GBP closing price fluctuations.

The COVID-19 pandemic has forced Indian engineering institutions (EIs) to bring their previous half-shut shades completely down. Fetching new admissions to EI campuses during the pandemic has become a ‘now or never’ situation for EIs. During crisis situations, institutions have struggled to return to the normal track. The pandemic has drastically changed students’ behavior and family preferences due to mental stress and the emotional life attached to it. Consequently, it becomes a prerequisite, and emergencies need to examine the choice characteristics influencing the selection of EI during the COVID-19 pandemic. The purpose of this study is to critically examine institutional influence and pandemic influence due to COVID-19 that affects students’ choice about an engineering institution (EI) and consequently to explore relationships between institutional and pandemic influence. The findings of this quantitative research, conducted through a self-reported survey, have revealed that institutional and pandemic influence have governed EI choice under the COVID-19 pandemic. Second, pandemic influence is positively affected by institutional influence. The study demonstrated that EIs will have to reposition themselves to normalize pandemic influence by tuning institutional characteristics that regulate situational influence and new enrollments. It can be yardstick for policy makers to attract new enrollments under pandemic situations.

Symmetry in biological and physical systems is a product of self-organization driven by evolutionary processes, or mechanical systems under constraints. Symmetry-based feature extraction or representation by neural networks may unravel the most informative contents in large image databases. Despite significant achievements of artificial intelligence in recognition and classification of regular patterns, the problem of uncertainty remains a major challenge in ambiguous data. In this study, we present an artificial neural network that detects symmetry uncertainty states in human observers. To this end, we exploit a neural network metric in the output of a biologically inspired Self-Organizing Map, the Quantization Error (SOM-QE). Shape pairs with perfect geometric mirror symmetry but a non-homogenous appearance, caused by local variations in hue, saturation, or lightness within and/or across the shapes in a given pair produce, as shown here, longer choice RT for ‘yes’ responses relative to symmetry. These data are consistently mirrored by the variations in the SOM-QE from unsupervised neural network analysis of the same stimulus images. The neural network metric is thus capable of detecting and scaling human symmetry uncertainty in response to patterns. Such capacity is tightly linked to the metric’s proven selectivity to local contrast and color variations in large and highly complex image data.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Tuberculosis (TB) associated with diabetes (DM) is a growing problem, particularly in low and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment with isoniazid (INH) or rifampicin (RIF) in people with DM. Participants were assigned six months of INH 300mg/day plus pyridoxine 75mg or three months of RIF 600mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TB preventive treatment is not safe enough to be considered a universal indication to patients with DM and LTBI. These results underline the need to search for alternative TB prevention in DM patients with better safety profiles.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Education for Sustainable Development (ESD) is considered vital to the success of the United Nations’ Sustainable Development Goals. Systems Thinking has been identified as a core competency necessary to incorporate into ESD. Systems Thinking orientated ESD learning tools, established methods of assessment of sustainability skills, and studies to demonstrate effectiveness of such learning tools, are all lacking. There is a wealth of experience in the System Dynamics field regarding the application of Systems Thinking and simulation to environmental problems, sustainability and systems education. Many System Dynamicists regard simulation as essential for teaching Systems Thinking. The substantial body of research into the design of effective simulation-based learning environments (SBLEs) can also inform ESD initiatives. This research describes a randomised controlled trial (n=106) to investigate whether an online sustainability learning tool that incorporates Systems Thinking and System Dynamics simulation increases understanding of a specific problem and supports transfer of knowledge to a second problem with a similar systemic structure. The effects of Systems Thinking and simulation were tested separately and in combination. The learning tool was designed for a single online learning session. Simulation was found to increase ESD learning outcomes significantly, and also to support transfer of skills, although less significantly.

The airport ground handling service (AGHS) equipment vendor selection (AGHSEVS) problem is critical for ramp work safety management, because AGHS equipment malfunctions affect airport ramp work safety. Appropriate vendor selection can prevent aircraft damage and delays in airlines schedules, and ensure reliable and high-quality ground handling service. The AGHSEVS problem is a time-consuming and complex process that requires professional knowledge and experience to make judgments. Specifically, AGHSEVS is a multi-criteria decision-making (MCDM) problem. Previous research has seldom integrated MCDM methods with linear and goal programming to solve the AGHSEVS problem. The objective of this study was to develop a new system evaluation model for AGHSEVS by considering both qualitative and quantitative methods. We test the proposed approach on an AGHS company in Taiwan.

This study investigates the factors influencing the choice of online and offline shopping trips and their impacts on urban transportation, environment, and economy in Tehran, Iran. A questionnaire survey was conducted to collect data from 1,000 active e-commerce users who made successful orders in both online and offline services in the last 20 days of 2021 in areas 2 and 5 of Tehran. A deep neural network model was developed to estimate the type of shopping trip based on 10 indicators, such as age, gender, car ownership, delivery cost, product price, etc. The performance of the model was compared with three other algorithms: MLP, decision tree, and KNN. The results showed that the deep neural network model had the highest accuracy of 95.63%. The most important factors affecting the choice of shopping trips were delivery cost, delivery time, and product price. This study provides insights for transportation planners, e-commerce managers, and policymakers to design effective strategies for reducing transportation costs, pollutant emissions, urban traffic, and increasing user satisfaction and sustainable development.

The recent consecutive economic and social crises impose sustainable “form farm to fork” food chain management to feed the global population. In this study we investigate young consumers (Gen Z) price perceptions in purchasing foods in Greece to find out the determinants ensuring sustainable, future food consumption. We used 8 overall price perceptions determinants, 5 with negative roles namely value &amp; price consciousness, coupon &amp; sales proneness, price mavenism and 3 with positive roles namely price-quality, price-value, and prestige-sensitivity for the formation of the study’s questionnaire. A total of 514 students (Gen Z by 85%) answered the questionnaire, promoted through the Google platform during September and October 2023. Data was analyzed with statistical tools, combining cross and chi-square tests. Between the negative determinants the “value consciousness” price perceptions (71.02%) were the most important parameters in purchasing food, followed by “price consciousness” (55.02%) parameters. “Coupon proneness” by 48.4% and “sales proneness” by 49% parameters were equally lower to the participants’ references, while “price mavenism” parameters were minimally preferred by only 26.4% by the participants. Participants exhibited major preference for “value to price” interconnection (66.7%) such as for good value for money, value exceeding its price, overvalued low priced foods, while their preference for “quality to price” interconnection was significantly lower (48.8%) such as for getting what you pay, more money for better quality, priced quality foods. The “prestige- sensitivity” price perception was out of their preference for food purchase (only 7.1%). Our findings indicate that young consumers (Gen Z) pay more attention to the value negative and positive parameters concerning price perceptions for food purchase rather than quality, coupons &amp; sales, low price, and mavenism or even prestige of the foods. This means that value issues such as the perceived environmental impact (green value), the climate crisis, the social signaling potential and others are high in their concerns for their future including their price perceptions for food purchase.

AbstractIntroduction: Increasing knowledge of obstetric danger signs (ODS) and encouraging birth preparedness and complication readiness (BPCR) practices are strategies to increase skilled maternal health service utilization in low-income countries. One of the methods to increase mothers' knowledge about ODS and promote BPCR practice is through health education intervention (HEI). However, the effect of context-specific community-based health education led by women's groups on these outcomes has not been comprehensively studied, and the existing evidence is inconclusive. Thus, we aimed to evaluate the effect of a context-specific community-based HEI led by women's groups on mothers' knowledge regarding ODS and BPCR practices in southern Ethiopia.Methods: An open-label, two-arm parallel group cluster-randomized controlled trial was conducted from January to August 2023 on pregnant women from 24 clusters (kebeles) (12 interventions and 12 controls) in the northern zone of the Sidama region. The Open Data Kit smartphone application was utilized to collect data. The intention-to-treat analysis was used to compare outcomes between groups. We fitted multi-level mixed-effects modified Poisson regression with robust standard error to account for between and within cluster effects. Results: One thousand and seventy pregnant women (540 in the intervention and 530 in the control clusters) responded to this study, making the overall response rate 95.02%. Excessive vaginal bleeding (94.3% in the interventional group vs. 88.7% in the control group) was the commonest ODS mentioned during childbirth. Overall, 68.7% of women in the intervention group and 36.2% of mothers in the control group had good knowledge of ODS (P-value < 0.001). Saving money and materials (97.1% in the interventional group vs. 92.7% in the control group) was the most frequently practiced BPCR plan. Overall, 64.3% of women in the intervention group and 38.9% of mothers in the control group practiced BPCR (P-value < 0.001). HEI significantly increased overall knowledge of ODS (adjusted risk ratio [ARR]: 1.71; 99% CI: 1.14-2.57) and improved overall BPCR practice (ARR: 1.55; 99% CI: 1.02-2.39). Conclusions: A community-based HEI led by women's groups improved mothers' knowledge regarding ODS and BPCR practices in a rural setting in southern Ethiopia. Interventions designed to increase women's knowledge of ODS and improve BPCR practice must implement context-specific, community-based HEI that aligns with World Health Organization recommendations. Trial registration: NCT05865873

We introduce linear probing hashing schemes that construct a hash table of size $n$, with constant load factor $\alpha$, on which the worst-case unsuccessful search time is asymptotically almost surely $O(\log \log n)$. The schemes employ two linear probe sequences to find empty cells for the keys. Matching lower bounds on the maximum cluster size produced by any algorithm that uses two linear probe sequences are obtained as well.

Background: Globally, women’s responsibility for unpaid care work (UCW) remains a barrier to gender equality and women’s empowerment. Rwanda, a low-income country, has a legal and policy framework for promoting gender equality but remains a patriarchal society with women responsible for UCW. Reseaux des Femmes, a local NGO, has been delivering a programme targeted at reducing and redistributing the UCW of women with the objective of gender transformational change. However, there has been no impact evaluation of their intervention to date. Methods/Design: The impact evaluation will be a proof-of-concept critical realist cluster control trial (CRcCT) to evaluate for which women, how and under what circumstances the intervention reduces and redistributes women’s UCW, promote gender equality and women’s empowerment, and improves women’s quality of life. Four clusters of villages in each of five districts in Rwanda will be randomly allocated to the intervention or control arms, and all eligible households, those headed by a couple with at least one child under 12 years, will be recruited. This will yield a sample of around 550 intervention households and 550 control. Discussion: This protocol describes the design of mixed-methods research to evaluate an intervention in Rwanda aimed at reducing and redistributing the time women spend on UCW, thereby promoting gender equality and women’s empowerment. This paper will contribute to our understanding of interventions for transforming gender relations from a scholarly perspective. From a policy perspective, it will act as a proof of concept of Reseaux des Femmes’ Programme.

Low vitamin D status in winter permits viral epidemics. During winter, people who do not take vitamin D supplements are likely to have low serum 25-hydroxyvitamin D [25(OH)D] concentrations. Vitamin D can reduce the risk of viral epidemics and pandemics in several ways. First, higher 25(OH)D concentrations reduce the risk of many chronic diseases, including cancers, cardiovascular disease, chronic respiratory tract infections (RTIs), diabetes mellitus, and hypertension. Patients with chronic diseases have significantly higher risk of death from RTIs than otherwise healthy people. Second, vitamin D reduces risk of RTIs through three mechanisms: maintaining tight junctions, killing enveloped viruses through induction of cathelicidin and defensins, and reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia. Observational and supplementation trials have reported higher 25(OH)D concentrations associated with reduced risk of dengue, hepatitis, herpesvirus, hepatitis B and C viruses, human immunodeficiency virus, influenza, respiratory syncytial virus infections, and pneumonia. Results of a community field trial reported herein indicated that 25(OH)D concentrations above 50 ng/ml (125 nmol/l) vs. <20 ng/ml were associated with a 27% reduction in influenza-like illnesses. From the available evidence, we hypothesize that raising serum 25(OH)D concentrations through vitamin D supplementation could reduce the incidence, severity, and risk of death from influenza, pneumonia, and the current COVID-19 epidemic.

Online and offline shopping trip have different impacts on various aspects of urban life, such as e-commerce, transportation systems, and sustainability. Therefore, it is important to evaluate the factors that influence their choices. We use a hybrid machine learning model that combines a gray wolf optimization algorithm and a deep convolutional neural network to estimate shopping trip based on a survey of 1,000 active e-commerce users who made successful orders in both online and offline services in the last 20 days of 2021 in areas 2 and 5 of Tehran. The gray wolf optimization algorithm performs feature selection and hyperparameter tuning for the deep convolutional neural network, which is a powerful deep learning model for image recognition and classification. The results show that our model achieves an accuracy of 97.81% with an MSE of 0.325 by selecting seven out of ten features. The most important features are delivery cost, delivery time, product price, car ownership. In addition, comparing the performance of the proposed method with other methods showed that the proposed algorithm with an accuracy of 97.81%, the accuracies of the single deep learning model, MLP neural network, decision tree, and KNN models were 95.63%, 90.0%, 86.49%, and 80.16%, respectively.

A few empirical examples document fixed alternative male mating strategies in animals. Here we focus on the polymorphism of male mating strategies in the ruff (Calidris pugnax, Aves Charadriiformes). In ruffs, three fixed alternative male mating strategies coexist and are signaled by extreme plumage polymorphism. We first present relevant data on the biology of the species. Then we review the available knowledge of the behavioral ecology of ruffs during the breeding season and we detail the characteristics of each of the three known fixed male mating strategies. We next turn to the exceptional quality results accumulated on both the structural and functional genomics of the ruff over the past few years. We show how much these genomic data can shed a new, mechanistic light on the evolution and maintenance of the three fixed alternative male mating strategies. We then look if there are sufficient indication to support frequency-dependent selection as key mechanism in maintaining these three strategies. Specifically, we search for evidences of equal fitness among individuals using each of the three strategies. Finally, we propose three lines of research avenues that will help to understand the eco-evolutionary dynamics of phenotypic differences within natural populations of this iconic model species.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

One important motivation for the implementation of the Water Framework Directive is the creation of non-market environmental benefits such as improved ecological quality, or greater opportunities for open-access river recreation via microbial pollution remediation. Pollution sources impacting on ecological or recreational water quality can be uncorrelated but non-market benefits arising from riverine improvements are typically conflated within benefit valuation studies. Using stated preference choice experiments, we seek to disaggregate these sources of value for different river users, thereby allowing decision makers to understand the consequences of adopting alternative investment strategies. Our results suggest anglers derive greater value from improvements to the ecological quality of river water, in contrast to swimmers and rowers for whom greater value is gained from improvements to recreational quality. We also find three distinct groups of respondents: a majority preferring ecological over recreational improvements, a substantial minority holding opposing preference orderings and a small proportion expressing relatively low values for either form of river quality enhancement. As such, this research demonstrates that the non-market benefits which may accrue from different types of water quality improvements are nuanced in terms of their potential beneficiaries and, by inference, their overall value and policy implications.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

While the importance of corporate governance has been broadly acknowledged in global financial markets and academic research, how to devise a practical evaluation system is relatively unexplored. This paper attempts to refine the Corporate Governance Evaluation System (CGES), constructed by the Taiwan Stock Exchange (TWSE) since 2014. The current CGES has several debatable issues in its complicated design (e.g., it comprises over 80 indicators in different types). To resolve those issues, this study invited ten senior domain experts (including several CEOs of financial holding companies) to retrieve 13 essential criteria from the CGES in four dimensions. And this study integrates several multiple criteria decision-making (MCDM) methods (i.e., Decision-making trial and evaluation laboratory (DEMATEL), modified VIKOR, DEMATEL-based analytical network process (DANP)) and the fuzzy evaluation technique to rank the exemplary companies. The obtained ranking is consistent with the one released from the CGES in 2017. This study conducted additional experiments to ensure the robustness of the findings. The newly devised model not only supports the ranking decisions but also provides a managerial guidance for companies to pursue systematic improvements. These findings enrich the understanding of corporate governance and contribute to gaining business sustainability for financial holding companies.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

Urban areas are centres of business and innovation. Freight transport is indispensable for the proper functioning of any modern urban society. Urban areas can’t function without an appropriate freight transport system, due to the need to replenish stocks of food and other goods in retail shops. The complexity of the decisions concerning implementation of measures to improve the movement of goods in the city requires tools designed to support this process. The purpose of this article is to introduce the possibility of applying the Analytic Hierarchy Process (AHP) as well as the Decision Making Trial and Evaluation Laboratory Method (DEMATEL) in choosing a set of measures and in analysing in the field of distribution logistics, which will help to solve the delivery problems and streamline the cargo flows in Szczecin, in the context of sustainable development.