Rivaroxaban and aspirin are commonly used antithrombotic agents that are used in combination for the prevention of coronary artery disease (CAD) and atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg Rivaroxaban twice daily with 75–100 mg aspirin daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to decrease the patient's pill burden and enhance medication adherence. The product formula was developed based on compatibility studies among the active ingredients and the active ingredients' compatibility studies. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants in the formula.

The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

This paper presents an extended Kalman filter derivation for loosely coupled GPS (Global Positioning System)/INS (Inertial Navigation System) integration based on quaternion attitude representation using the Earth-Centered Earth (ECEF) Frame. In this loosely coupling integration, both the position and velocity estimates from GPS receiver are used as the measurements to extended Kalman filter, and then they are integrated with inertial measurements from inertial measurement units (IMU) to estimate the attitude, position and velocity of an air vehicle. The velocity estimates which have centimeter level estimation error from the GPS receiver are used to improve the filter performance. For attitude estimation, the global attitude parameterization is given by a quaternion and a multiplicative quaternion-error approach is used to guarantee a normalization constraint of quaternion in the filter. Simulation results are shown to obtain the estimation of the attitude, position, velocity, biases and scale factors and to evaluate the performance of the EKF with the measurement combination composed of the two different t

Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.

This paper aims to introduce the notions of various types of Qc-contractions for which we establish some fixed circle and fixed disc theorems in the setting of metric spaces. Some illustrative examples are also provided to support our results. Moreover, we present some fixed circle and fixed disc results of integral type contractive self-mappings.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

Background: Computed tomography examinations have produced high radiation doses to patients, especially the CT brain. This study aimed to optimize the radiation dose and image quality in adult CT brain protocol. Materials and Methods: Images were acquired by Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). Image quality were also evaluataion by The AutoQA Plus software. Results: CT Number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. MTF showed a higher value in 100 and 120 kVp protocols, while high contrast spatial resolution showed a higher value in 80 and 100 kVp protocols. Low contrast detectability and CNR tended to increase when using high mAs, SNR and Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Conclusion: Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100-120 kVp, mAs ranging from 200-300 mAs, SNR level within the range of 0.7-1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.

Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients major Lyme symptoms remained in remission for a period of 25-30 months. In conclusion, Double dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/PTLDS, especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.

While there is a coordinated effort around reaching zero dose children and closing existing equity gaps in immunization delivery, it’s important that there is agreement and clarity around how ‘zero dose status’ is defined and what is gained and lost by using different indicators for zero dose status. There are two popular approaches used in research, program design, and advocacy to define zero dose status: one uses a single vaccine to serve as a proxy for zero dose status, while another uses a subset of vaccines to identify children who have missed all routine vaccines. We provide a global analysis utilizing the most recent publicly available DHS and MICS data to compare the number, proportion, and profile of children 12 to 23 months who are ‘penta-zero dose’ (have not received the pentavalent vaccine), ‘truly’ zero dose (have not received the BCG, polio, pentavalent, and measles vaccines), and ‘misclassified’ zero dose children (those who are penta-zero dose but have received at least one other vaccine). Our analysis includes 194,829 observations from 82 low- and middle-income countries. Globally, 14.2% of children are penta-zero dose and 7.5% are truly zero dose, suggesting that 46.5% of penta-zero dose children have had at least one contact with the immunization system. While there are similarities in the profile of children that are penta-zero dose and truly zero dose, there are key differences between the proportion of key characteristics among truly zero dose and misclassified zero dose children, including access to maternal and child health services. By understanding the extent of connection zero dose children may have with the health and immunization system and contrasting it with how much the use of a more feasible definition of zero dose may underestimate the level of vulnerability in the zero dose population, we provide insights that can help immunization programs design strategies that better target the most disadvantaged populations. If the vulnerability profiles of the truly zero dose children are qualitatively different from that of the penta zero dose children, then failing to distinguish the truly zero dose populations, and how to optimally reach them, may lead to the development of misguided or inefficient strategies for vaccinating the most disadvantaged population of children.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and &lt;14 Gy). Results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8% respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (P = 0.628), while Group 2 (&lt;14 Gy) exhibited significantly lower PTE (P = 0.039). The study concludes that SRS with a radiation dose &lt;14 Gy demonstrates comparable tumor control with reduced toxicity, advocating for consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

This study investigated the influence of nutrient inputs and their timing on saffron yield and quality. The study was conducted from 2016 to 2020 and involved the application of eight different fertilization treatments at various stages of saffron growth. These treatments included single doses in Autumn (A), Winter (W), and Spring (S); double doses in Winter-Spring (AW), Autumn-Spring (AS), and Winter-Spring (WS); and a triple dose in Autumn-Winter-Spring (AWS). A control group (C) received no fertilizer. A compound fertilizer with a 15-15-15 composition was applied across all treatments, with nitrogen (N) rates of 67.5 kg/ha for single doses (A, W, S), 135 kg/ha for double doses (AWF, ASF, WSF), and 202.5 kg/ha for the triple dose (AWSF). Similar rates were applied for phosphorus (P) and potassium (K). The findings demonstrated that fertilization generally enhanced saffron attributes. The triple dose treatment yielded the most effective results. The timing of fertilization also played a crucial role, as split applications during different growth stages led to higher production especially winter fertilization. However, spring fertilization had limited impact due to decreased plant activity and reduced nutrient absorption during that period. Although the yield increased, the qualitative aspects of saffron, including color (crocin), taste (picrocrocin), and aroma (safranal), were not significantly influenced by the fertilization treatments. Nevertheless, these attributes remained within the natural limits defined by ISO-3632, indicating that fertilization practices did not compromise saffron quality. Our study highlights the significance of nutrient inputs and their timing in optimizing saffron yield. It provides valuable insights for developing efficient fertilization programs to enhance saffron production while preserving its quality characteristics.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

Background: Although metastatic GCT is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remains lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. Methods: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. Results: Respondents included 30 staff; from 18 cancer centers across provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available for (70%) in 13 centers. HDCT regimen used included carboplatin and etoposide for 2 cycles (76% in 7 centers), 3 cycles (6% in two centers), and the TICE protocol (11%, in 2 centers). “Bridging” CDCT was used by 65% respondents. Post HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%) and sur-veillance only (6.3%). Conclusions: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT.

In the European Union (EU), cannabidiol products require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are under assessment at the European Food Safety Authority (EFSA). During the initial assessment of the application files, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) located several knowledge gaps in their 07 June 2022 statement on safety of cannabidiol as a novel food that need to be addressed before the evaluation of CBD can be concluded. Namely, the effect of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system needs to be clarified. Nevertheless, the available literature allows a benchmark dose (BMD)-response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers found increases in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a study at 4.3 mg/kg bw/day, which was defined by EFSA NDA panel as a lowest observed adverse effect level (LOAEL). The EFSA NDA panel currently concluded that the safety of CBD as a novel food cannot be evaluated, leading to a so-called clock stop of the applications until the applicants provide the required data. Meanwhile, the authors suggest that CBD products still available as food supplements on the EU market despite the lack of authorisation must be considered as “unsafe”. Products exceeding a health-based guidance value of 10 mg/day must be considered as being “unfit for consumption” (Article 14(1) and (2) (b) of Regulation No 178/2002), while the ones in exceedance of the human LOAEL must be considered “injurious to health” (Article 14(1) and (2) (a) of Regulation No 178/2002).

Drying grains in a fixed bed can be an interesting alternative to prevent undesirable breaks and fractures of solids due to mechanical shocks, something that cannot be avoided when drying in moving beds. A disadvantage of fixed bed drying is that there can be significant gradients in the critical variables if the layer of particulate solids is thick. This work shows that periodically changing the direction of drying air flow is an effective technique to reduce differences within the bed and allow better uniformity of the product. Drying in a thick layer of 10 cm of sorghum grains was carried out at 50 and 60oC for air flow velocity of 2.1 m.s-1. The results showed that despite increasing the total drying time, the technique actually allowed a significant decrease in the temperature gradients and moisture content of the sorghum grains. The change in direction of the air flow caused the drying front to be displaced, sometimes towards the top, sometimes towards the base of the bed. At 50oC, drying lasted a total of 240 min, bringing the sorghum grains to an average overall moisture content of 0.13 on a dry basis.

In this article, we introduce a relatively new concept of multi-valued (θ;R)-contractions and utilize the same to prove some xed point results for a new class of multi-valued mappings in metric spaces endowed with an amorphous binary relation. Illustrative examples are also provided to exhibit the utility of our results proved herein. Finally, we utilize some of our results to investigate the existence and uniqueness of a positive solution for the integral equation of Volterra type.

The purpose of this article is to characterize the Caristi type mapping by the absolute derivative. The equivalences of the Caristi mapping with contraction mapping is discussed too. In addition, it was shown that the contraction mapping can be characterized by its absolute derivative.

In this paper, the notion of θ∗-weak contraction is introduced, which is utilized to prove some fixed point results. These results are helpful to give a positive response to certain open question raised by Kannan [Amer. Math. Monthly 76:1969] and Rhoades [Contemp. Math. 72:1988] on the existence of contractive definition which does not force the mapping to be continuous at the fixed point. Some illustrative examples are also given to support our results. As applications of our result, we investigate the existence and uniqueness of a solution of non-linear matrix equations and integral equations of Volterra type as well.

The calculation and visualization of the dose field in the decommissioning of nuclear facilities is one of the important functions of the decommissioning virtual simulation system, which can provide accurate and intuitive radiation field distribution and play an important role in determining the demolition plan and protecting personnel during the engineering implementation process. This article investigates the development of dose field calculation and visualization in the reactor decommissioning virtual simulation systems, and preliminarily proposes a technical plan suitable for the development of the decommissioning dose field calculation and visualization display programs for the first Heavy Water Research Reactor (HWRR) in China. Besides, the applicability of the selected scheme is analyzed, the functional requirement and development direction of the HWRR reactor decommissioning dose field calculation and visual display module are preliminarily determined. Furthermore, the reactor vessel of HWRR reactor is modeled and the dose field distribution was calculated and visualized. This research can provide technical support for the development of the decommissioning simulation system for the first HWRR reactor in China.

The total ionizing dose (TID) effect significantly impacts the electrical parameters of fully depleted silicon on insulator (FDSOI) devices and even invalidates the on-off function of devices. At present, most of the irradiation research on the circuit level is focused on the single event effect, and the research on the total ionizing dose effect is very little. Therefore, this study mainly analyzes the influence of TID effects on a CMOS inverter circuit based on 22 nm FDSOI transistors. First, we constructed and calibrated an N-type FDSOI metal-oxide semiconductor (NMOS) structure and P-type FDSOI metal-oxide semiconductor (PMOS) structure. The transfer characteristics and trapped charge distribution of these devices were studied under different irradiation doses. Next, we studied the TID effect on an inverter circuit composed of these two MOS transistors. The simulation results show that when the radiation dose is 400 krad (Si), the logic threshold drift of the inverter is approximately 0.052 V. These results help further investigate the impact on integrated circuits in the irradiation environment.

Background: Manoka Health District (MHD), an enclaved archipelago district in Cameroon, is home to about 1,732 under-2 children. Over 90% of these children have not received a single dose of any vaccine. In this paper, we explored the reasons for the high proportion of zero-dose children in this district so as to generate information that policymakers can use to develop context-specific interventions to boast coverage for routine immunization (RI) in this remote fishing island Methodology: We collected qualitative data via key informant interviews (KII) and focused group discussions (FGD) and analyzed it using thematic analysis. Participants for KII were selected using purposive sampling, and a snowballing approach helped to recruit an intermixed population of locals and immigrants for FGDs. Results: MHD is a hard-to-reach zone with a lone health facility that lack a functional cold chain equipment to cover the 47 islets of the district. Diurnal floods, long distance, sea turbulence, infrastructural and resource constraints, and immigrant population without residence permits hinders optimal childhood vaccination. Insufficient community health workers and lack of proper community engagement with feedback loops hamper effective communication and vaccine uptake during campaigns and outreaches. The reasons for vaccination hesitancy included hospital-based vaccination preference over home-based vaccination, fear of post-vaccination fever, rumors, repeated postponement of the vaccination schedules, and refusal by some ethnic group leaders. Conclusion: This study revealed context-specific reasons for zero-dose childhood vaccination status in MHD. These findings should be leveraged to design tailored interventions to raise RI in MHD and similar under-vaccinated communities. Keywords: zero-dose, childhood vaccination, missed communities, Cameroon

Imidazoline derivatives, such as xylometazoline, naphazoline, tetryzoline, tramazoline or oxymetazoline play an important pharmacological role as nasal drops in the symptomatic treatment of rhinitis. When comparing the toxicological data of these substances, it is noticeable that Oxymetazoline has an LD₅₀ value which is two orders of magnitude lower than all other imidazoline derivatives. Thus, ten vials of commercially available oxymetazoline nasal drops already contain a lethal amount. An explanation for this unusually high toxicity has not yet been found.

Background: We considered a problem of inference in epidemiology when cumulative exposure is the true dose metric for disease, but investigators are only able to measure its duration on each subject. Methods: We undertook theoretical analysis of the problem in the context of a continuous response caused by cumulative exposure, when duration and intensity of exposure follow log-normal distributions, such that analysis by linear regression is natural. We present a Bayesian method to adjust duration-only analysis to incorporate partial knowledge about the relationship between duration and intensity of exposure and illustrate this method in the context of association of smoking and lung function. Results: We derive equations that (a) describe under what circumstances bias arises when duration of exposure is used as a proxy of cumulative exposure, (b) quantify the degree of such bias and loss of precision, and (c) describe how knowledge about relationship of duration and intensity of exposure can be used to recover an estimate of the effect of cumulative exposure when only duration was observed on every subject. Conclusions: Under our assumptions, when duration and intensity of exposure are either independent or positively correlated, we can be more confident in qualitatively interpreting the direction of effects that arise from use of duration of exposure per se. To make reliable inference about the magnitude of effect of cumulative exposure on the outcome, we can use external information on the relationship between duration and intensity of exposure even if intensity of exposure is not available at the individual level.

Oncological patients need the proper doses of medications to facilitate their recovery. The two basic approaches used in dosing Monoclonal Antibodies (mAbs) are fixed-dose combination and variable dosing. In Fixed-Dose Combination Drugs (FDCs), two or more active components are combined in a single formulation at a predetermined dose. Variable dosage, which has long been the industry standard, is the polar opposite of this approach. The body changes over time; the Body Surface Area (BSA) in square meters is often used as a Measure (m2). This study uses a systematic review. Most mAbs used in oncology are predominantly given as cytotoxic anticancer drugs using body-size-based (variable) regimens. Despite the benefits of fixed-dose, variable dosing has become the industry standard, despite being criticized for ineffectiveness. While variable dosing has some advantages, the prevalent view is that continuous dosing has significant advantages based on the balance of probabilities. After assessing each alternative, including its benefits and drawbacks, history of use, and suitability in the current context, fixed dosing emerges as a viable option.

In this paper, it is proved that s-iteration with error and Picard-Mann iteration with error iterative processes converge strongly to the unique fixed point of Lipschitzian strongly pseudo-contractive map. This convergence is almost -stable and -stable. Applications of these results to the operator equations, where is a strongly accretive and accretive mappings of into itself.

We introduce the notion of generalized contraction on dualistic partial metric spaces. A fixed point theorem for mappings satisfying above mentioned contraction is obtained. Some consequences of our result are obtained. We construct an example to demonstrate the effectiveness of our result among the corresponding results in partial metric spaces. Our results provide substantial generalizations and improvements of several well known results existing in the comparable literature. We discuss an application of our fixed point results to show the existence of solution of functional equations.

Tunneled central venous catheters (CVC) are mainly considered as rescue vascular access option in dialysis but still used in about one quarter of prevalent patients worldwide as being associated with poor performances and higher risks. Study design. In this retrospective single-center study, we aimed to report on clinical performances achieved with high-flow tunneled CVC (DualCath, DCath) and compared it with arteriovenous accesses (AVAs; AV fistula, AV graft, Thomas Shunt) in a hospital-based dialysis unit. Methods. Sixty-eight stage 5 chronic kidney disease dialysis dependent patients (CKD5D) receiving high volume hemodiafiltration were followed-up for 30 months. The study consisted of two phases: baseline cross-sectional and longitudinal follow-up of key performance indicators. Clinical performances consisting of effective blood flow and blood volume, recirculation, urea and ionic Kt/V and total Kt, ultrafiltration volume and percent reduction of ß2-M were measured monthly as part of quality control in our unit. Results. At baseline, effective blood flow with DCath was close to 400 ml/min, similar to AVAs. Recirculation with DCath (7%, 6-13%) was higher than AVAs. Diffusive dialysis dose delivered with DCath (spKt and eKt/V) and convective dialysis dose achieved with DCath were slightly lower than AVAs, but still much higher than recommended by guidelines. Percent reduction of ß2-M achieved with DCath was also 4 to 10% lower than AVAs. On longitudinal follow-up, main clinical performance indicators of DCath (total Kt and total ultrafiltration volume, L/session) were maintained very stable over time and close to those achieved with AVAs. Conclusions. As shown in this study, high-flow DualCath tunneled two single lumen silicone catheters may be used to deliver high volume hemodiafiltration in a reliable and consistent manner without compromising clinical performances. These results rely from the specific design of the two silicone cannulas and the strict adherence to best catheter practices.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

Vaccination has proven to be one of the most effective strategies against the COVID 19 pandemic. Several studies have evaluated and confirmed its effectiveness in different populations, particularly in reducing severe outcomes such as hospitalization and death. However, the potential of vaccination to protect against infection itself has been overlooked. The aim of this study was to determine the effectiveness of the booster dose in a sample of Colombian patients during the fourth wave of COVID-19 pandemic, which was associated with the emergence and predominance of the Omicron variant. A cross-sectional study was conducted on individuals who underwent RT-PCR testing for COVID-19 detection in a dedicated laboratory in Bogotá, Colombia, between December 30th 2021 and February 7th 2022. A total of 1,468 subjects were included in the study. The comparison between fully vaccinated individuals with a booster dose and those without the booster dose revealed a 28% reduction in the odds of infection (OR = 0.719 CI 0.531 - 0.971). Age (OR = 1,009 CI 1,001 - 1,018) and low economic status (OR= 1,812 CI 1,416- 2,319) were associated with an increased risk of infection.These findings suggest the need for booster vaccination in the general population to improve the prevention rates of SARS-CoV-2 infection and mitigate severe outcomes.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cells killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit of the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacting liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate reducing by 4 the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.

The new WHO Environmental Noise Guidelines for the European Region have recommendations for limiting noise exposure associated with adverse health effects. The limits are said to be based on a systematic review of existing evidence. This paper gives a systematic assessment of the presented evidence with respect to aircraft noise annoyance and demonstrates that the new guidelines are based on an arbitrary selection of existing studies comprising an imperfect and faulty set of data not representative for the general airport population.

In estimating logistic regression models, convergence of the maximization algorithm is critical, however, this may fail. Numerous bias correction methods for maximum likelihood estimates of the parameters have been conducted for cases of complete data sets and also longitudinal models. For binary response fixed effects panel data model, the conditional logit estimator is consistent for balanced data. When faced with missing covariates problem, researchers opt for various imputation techniques to make the data complete and without loss of generality consistent estimates still suffice asymptotically. For maximum likelihood estimates of the parameters for logistic regression in cases of imputed covariates, the optimal choice of an imputation technique which yields the best estimates with minimum variance is still elusive. The main aim of this paper is to examine the behaviour of the Hessian matrix with optimal values of the imputed covariates vector which will make the Newton-Raphson algorithm to converge faster through a reduced absolute value of the product of the score function and the inverse fisher information component. We focus on a method used to modify the conditional likelihood function through partitioning of the covariate matrix. We also confirm from the moduli of the Hessian matrices that the log likelihood of a panel data logistic model has a global maximum as the parameter estimates. Simulation results reveal that model based simulation perform better than classical imputation techniques yielding estimates with smaller bias and higher precision for the conditional maximum likelihood estimation of nonlinear panel models with single fixed effects.

Molecular diagnostics in healthcare relies increasingly on genomic and transcriptomic method-ologies and requires appropriate tissue specimens from which nucleic acids (NA) of sufficiently high quality can be obtained. Besides suration of ischemia and fixation type, NA quality depends on a variety of other pre-analytical parameters, like storage conditions and duration. It has been discussed that improper dehydration of tissue during processing influences quality of NAs and shelf-life of fixed tissue. Here we report on establishing a method to determine the amount of residual water in fixed, paraffin-embedded tissue (fixed by neutral buffered formalin, or a non-crosslinking fixative) and its correlation to the performance of NAs in qRT-PCR analyses. The amount of residual water depended primarily on the fixative type and the dehydration pro-tocol and, to a lesser extent on storage conditions and time. Moreover, we found that these pa-rameters were associated with the qRT-PCR performance of extracted NAs. Besides cross-linking of NAs and modification of nucleobases by formalin, hydrolysis of NAs by residual water was found to contribute to reduced qRT-PCR performance. The negative effects of residual water on NA stability are not only important for the design and interpretation of research, but must also be taken into account in clinical diagnostics where reanalysis of archived tissue from a primary tumour may be required, e.g., after disease recurrence. We conclude that improving shelf-life of fixed tissue requires meticulous dehydration and dry storage to minimize the degradative in-fluence of residual water on NAs.

In this paper, inspired by Jleli and Samet [journal of inequalities and applications 38 (2014) 2 1–8] we introduce two new classes of auxiliary functions and utilize the same to define (q, y)R-weak 3 contractions. Utilizing (q, y)R-weak contractions, we prove some fixed point theorems in the setting 4 of relational metric spaces. We employ some examples to substantiate the utility of our newly proved 5 results. Finally, we apply one of our newly proved results to ensure the existence and uniqueness of 6 solution of a Volterra-type integral equation.

A common reactor type in the chemical and process industry is the fixed-bed reactor. Accurate modeling can be achieved with particle-resolved Computational Fluid Dynamic (CFD) simulations. However, the underlying bed morphology plays a paramount role. Synthetic bed-generation methods are much more flexible and faster than image-based approaches. In this study, we look critically at the two different bed generation methods: Discrete Element Method (DEM) (in the commercial software STAR-CCM+) and the rigid-body model (in the open-source software Blender). The two approaches are compared in terms of synthetically generated beds with experimental data of overall and radial porosity, particle orientation, as well as radial velocities. Both models show accurate agreement for the porosity. However, only Blender shows similar particle orientation than the experimental results. The main drawback of the DEM is the long calculation time and the shape approximation with composite particles.

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

Background: External beam radiation therapy requires a sophisticated and laborious planning procedure. To improve the efficiency and quality of the planning procedure, machine learning predictions of the dose distributions have been introduced to speed up the planning procedure and to serve as quality assurance. The most recent dose prediction models are based on deep learning U-Nets that give good approximations of the dose in 3D almost instantly. It is our purpose to train a 3D dose prediction for glioblastoma VMAT treatment and test its robustness and sensitivity for the purpose of quality assurance of automatic contouring. Methods: From a cohort of 125 glioblastoma (GBM) patients, VMAT plans were created according to a clinical protocol. The initial model was trained on a concatenated 3D U-Net. A total of 60 cases were used for training, 15 for validation and 20 for testing. The prediction model was tested for sensitivity to dose changes according to realistic contour variations. Additionally, the model was tested for robustness by exposing it to a worst-case test set containing out-of-distribution cases.Results: The initially trained prediction model had a dose score of 0.94 Gy and a mean DVH score for all structures of 1.95 Gy. In terms of sensitivity, the model was able to predict the dose changes that occurred due to the contour variations with a mean error of 1.38 Gy.Conclusions: We obtained a 3D VMAT dose prediction model for GBM with limited data, providing good sensitivity to realistic contour variations. We tested and improved the model's robustness, by targeted updating the training set, making it a useful technique for dose awareness in the contouring evaluation and quality assurance.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

Abstract: Using adjuvants to optimize and increase the efficacy of herbicides is an acceptable manner to reduce herbicides undesirable impact on the environment in sustainable agriculture. In this study, it was demonstrated that the application of 0.1% of the non-ionic surfactant (NIS, Contact) and 0.5 L ha-1 of a crop oil concentrate (COC, Renol) did not improve the efficacy of rimsulfuron on Amaranthus retroflexus. In contrast, the same treatments enhanced performance and rainfastnes of rimsulfuron in Chenopodium album in pot expriments. Increasing non-ionic surfactant concentration to 1 L ha-1 increased rimsulfuron performance around 11-fold for Amaranthus retroflexus compared to around 3-fold for Chenopodium album. The same treatment, also reduced the rainfastness of rimsulfuron on Amaranthus retroflexus while improving the rainfastness of rimsulfuron on Chenopodium album. Measured ED50 and ED90 values of rimsulfuron indicated that the addition of the 0.2 L ha-1 of NIS improved the recommended (60 g ai. ha-1) and the reduced (30 g ai. ha-1) of rimsulfurom in field. The highest potato yield measured (60 tons per ha) when 60 g ai. ha-1 rimsulfuron was applied at three stages (S1, S4, and S7) without using a NIS; not significant differences were measured when the same dose of rimsulfuron was applied at the three (S1, S4, and S7) and two (S1, S4) stages with NIS.

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

The COVID-19 pandemic caused an unprecedented effect on national radiological investigations. Since the World Health Organization officially declared the COVID-19 as a global pandemic, health policies have been rapidly organized to limit the spread of the virus and decrease the risk of exposure. These restrictions, in combination with home-stay arrangements and the onset of economic recession. As a result of public policies, financial difficulties and patient fear, many radiology departments have suffered a significant reduction in diagnostic examinations with important implications for their economic stability. The aim of this work is to evaluate the economic impact of the COVID-19 pandemic in the Radiology Department of an infectious disease hospital.

Increasing genetic diversity in crop plants has been used for chemical mutagenesis. Through the application of various mutagenic agents, over 430 new varieties have been derived as rice mutants (Oryza sativa L.) Chemical mutagens such as ethyl methane sulphonate (EMS), diepoxybutane derivative (DEB), sodium azide, and gamma ray, x-ray, and quick neutron irradiation have been commonly used to induce a large number of functional variations in rice and others crops. Among chemical mutagens, ethyl methane sulfonate (EMS) is the alkylating agent most widely used in plants because it induces nucleotide substitutions to be extremely frequent, as detected in various genomes. In this study, seeds of potential genotype of the popular variety, (Oryza sativa L. Super Basmati variety) were treated with EMS at concentrations of 0.25%, 0.50%, 0.75%, 1% and 1.5%. Various measurements on the M1 generation determined EMS sensitivity. As concentration of applied EMS increased, will decrease in germination, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility under field conditions were observed in M1 generation as compared to the non-treatment control. Emergence, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility also decreased with increases in EMS mutagenesis in an approximately linear fashion. The LD₅₀ values were observed based on growth reduction of seedlings after EMS treatment with 0.25% and 0.50% on the rice variety (Oryza sativa L. spp.).

Local anaesthetic agents suppress action potentials in excitable tissues by blocking voltage-gated sodium channels. In doing so they inhibit the depolarisation of nociceptive nerve fibres and so prevent the transmission of pain impulses. UK legislation allows HCPC-registered Podiatrists with POM-A annotation access to six local anaesthetic drugs and two of these with the addition of adrenaline. The use of local anaesthetia has transformed the treatment of nail pathology by Podiatrists. In the UK, the drug of choice in podiatric practice is 3% mepivacaine hydrochloride: it is a good choice of drug for digital anaesthesia. This paper will review the chemistry, pharmacology and dose calculation of mepivacaine, and challenge some of the orthodoxy over the rigid calculation of maximum safe dosages.

Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO₂, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO₂ upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO₂ ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO₂. Five patients were discharged (median 6^th day, range 2^nd-14^th day), and four patients died (median 7^th day, range 3^rd-10^th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

Ozonated oil has several benefits for humans, as it contributes to numerous interventions, maintaining the quality of life and the well-being of individuals. Being a natural product, it has few or almost no side effects. Thus, the study aimed to verify the sensitivity and/or resistance of fixed o “Ozonated” and “Non-Ozonated” oils from Mauritia flexuosa (Buriti), Carapa guaianensis (Andiroba) and essential “Ozonated” oils from Menta piperita (Mint), Eugenia caryophyllus (Clove) in different concentrations, against internationally known bacteria from the American Type Culture Collection – ATCC, comparing with the “Non-Ozonated” versions of the respective oils, using the Agar diffusion technique. Thus, it is evident that the ozonation of the fixed oils of Buriti and Andiroba, as well as the essential oils of Mint and Clove, provided significant results, although they were statistically different. The Buriti and Andiroba oil were ineffective in inhibiting microorganisms. On the other hand, the essential oil of Mint and Clove obtained similar activity of inhibition of microorganisms. With regard to Ozonation, the Essential Oil of “Ozonated” Clove provided greater activity than the “Non-Ozonated” one, which inhibited only one tested microorganism, in addition to producing changes in its chemical composition, requiring individualized studies for the ozonation of each essential oil.

Photovoltaic shading devices (PVSDs) have the dual function of providing shade and generating electricity, which can reduce building energy consumption and improve indoor daylighting levels. This study adopts a parametric performance design method and establishes a one-click simulation process by using the Grasshopper platform and Ladybugtools. The research focuses on the effect of dynamic PVSDs on daylighting and energy consumption in an office building in Qingdao. Through simulation, the study calculates the monthly energy consumption and useful daylight illuminance (UDI) under different inclination angles and installation heights of PVSDs. And the optimal configuration of PVSDs for each month under three dynamic strategies (rotation, sliding, and hybrid) is determined. Additionally, different control strategies and fixed PVSDs are compared to clarify the impact of various control strategies on daylighting and energy consumption. The findings reveal that, compared to no shading, dynamic PVSDs in rotation strategy (with an installation height of 0 m), sliding strategy (with an inclination angle of 20°), and hybrid strategy can achieve energy savings of 32.13%, 47.22%, and 50.38%, respectively. They can increase the annual average UDI by 1.39%, 2.8%, and 3.1%, respectively.

Monge-Ampere equations have important research significance in many fields such as geometry, convex geometry and mathematical physics. In this paper, under some superlinear and sublinear conditions, the existence of nontrivial solutions for a system arising from Monge-Ampere equations with two parameters is investigated based on Guo-Krasnosel'skii fixed point theorem. In the end, two examples are given to illustrate our main results.

Bambara groundnut (BG) (Vigna subterranean L. verdc) is a highly nutritious and economically important leguminous crop of African origin that forms symbiotic relationships nitrogen fixing rhizobia, but it has a low yield. Currently, there is paucity of information on effective rhizobium inoculant, (to improve the yield), for BG which are cheaper and safer alternatives to chemical fertilizers. Indigenous rhizobia strains were trapped from 54 farm soils collected at three Nigerian states (Niger, Kaduna and Kano). Six selected rhizobium strains (Bradhyrhizobium spp) were identified using 16S rDNA sequencing, applied as inoculant in field experiment using completely randomized block design and compared with USDA110 strain (Bradhyrhizobim japonicum), urea fertilizer and un-inoculated plants on 2 selected BG varieties (TVSU1248 and TVSU 631). Nutrient utilization and nitrogen fixation in plants were determined at 6 weeks while leaf chlorophyll was determined forth-nightly. Seed yield was determined at maturity. The strains increased the %nitrogen (1.33±0.10 - ≥1.37±0.05), and %phosphorous (0.48±0.02 - ≥0.51±0.02), %nitrogen fixed (21.07±2.38 - ≥61.30±6.13), nodulation (72.50±21.075 - 154.00±23.79) and leaf chlorophyll were ≥49.74±1.47mg/L, ≥51.82±1.86mg/L and ≥49.65±1.56mg/L at 2nd, 4th and 6th week after planting respectively and the yield of BG (from average of 398.6 Kgha-1 to 1454.725 Kgha-1). Seed yield was highest (1869.85±273.68 Kgha-1) in BG variety TVSU1248 using BN5 strain. Indigenous Bambara-symbiotic strains significantly increased the seed yields, and plant nutrient, showing their potential as use for inoculant to improve the yield of Bambara groundnut.

Recently, Li et al [1] investigated the nonlinear Langevin equations existence including two fractional orders with infinite-point boundary conditions. It has shown that the outcomes given it does count on the solution form for which it has boundary values. It means that their solution needs more to be in the final step. In current work, we will have discussion about the existence and uniqueness for the same boundary conditions by investigating the closely explicit solution form that has no boundary values. Numerical example is supported to have more vision to compare the between new and previous results. It turns out that our results are superior.

In this paper, we consider with a class of system of differential equations whose argument transforms are involution. In this an initial value problem for a differential equation with involution is reduced to an initial value problem for a higher order ordinary differential equation. Than either two initial conditions are necessary for a solution, the equation is then reduced to a boundary value problem for a higher order ODE.

The effects of the surface waves generated by the wind have a significant effect on the currents. A wave current coupled model plays an important role in the design of offshore structures. The interaction between fluids such as incompressible ocean waves and current and offshore structures is significant with many real-time applications in offshore engineering. These coupled models can be applied to Offshore Floating Production Operating and offloading (FPSO), Wind or current turbines and offshore pipelines. The complex issues related to the design are analyzed by using Computational Fluid Dynamics, which requires an investigation of the multiphase flow between wave and current and the structure which is considered restrictive due to the computational cost. If viscous effects are neglected then the single-phase flow models have been recommended, where wave-current interaction have been modelled successfully. Models have been developed where velocities and pressure are computed and the results can be verified with the experimental results available in the literature. In this study the existing numerical methods, mesh types are discussed along with their coupling methods. Here single-phase and multiphase models with small and medium movement are reviewed and their applications are highlighted.

In the present study, Electrocoagulated Metal Hydroxide Sludge (EMHS) was analyzed as adsorbent material to remove both fluoride ion (F-) and arsenic V (As(V)) from aqueous effluents. This material was generated during an electrocoagulation process using Aluminum anode. It was characterized by using specific surface areas and the surface morphology was studied by scanning electron microscopy (SEM). Adsorbent fixed-beds are generally studied to remove different class of contaminants. EMHS was evaluated using a continuous flow rate column test with an experimental design. The effect of initial concentration of F- (2.5–10 mg L⁻¹) and the Empty Bed Contact Time (EBCT (0.4–0.8 min)) was studied following a central composite design methodology. The experimented parameters had a significant influence on saturation time, breakthrough volume, and breakthrough time. A response surface analysis was a tool for analyzing the adsorption study, showing interactions that are complicated to identify by others methods. The results, here reported, revealed that EMHS is an efficient and promising adsorbent material in order to remove F- and As(V) from water contaminated by these pollutants.

The paper aims to investigate on the determinants of the capital structure of the Italian SMEs and it is based on a large panel of Italian manufacturing SMEs observed in the years 2001-2013. The analysis achieves a comparative investigation between the capital structure of the firms belonging in the Southern region, the so-called Italian Mezzogiorno that is the slow growing area of the country, and the firms of the Center-northern region of Italy, that is the more developed area of the country. Fixed effect panel techniques applied to the several standard leverage models allows to reaffirm some distinctive features showing differences of the financial behavior of regional firms.

The Hepatitis B virus, chronically infects over 240 million persons worldwide. The Hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 hours of life followed by a minimum of 2 subsequent doses. In October 2021, Antigua and Barbuda, through it’s only public hospital - the Sir Lester Bird Medical Centre, instituted a hospital based Hepatitis B vaccine birth dose policy. Timely birth dose coverage was 72% and total birth dose coverage 81%. 10.5% of parents refused the hepatitis b – birth dose, of which 76% either felt uncomfortable or preferred to wait. 100% of babies born before arrival received timely vaccine administration, likewise 100% of Hepatitis B exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. A maternal Hepatitis B surface antigen result was available for 90.4% of mothers. Barriers to timely birth dose administration included vaccination hesitancy, gaps in healthcare worker knowledge, and the consistent supply of Hepatitis B vaccine. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother to child transmission of hepatitis B by 2030 possible.

To determine the impacts of metabolizable energy levels on the performance indices of geese and to forecast the ideal range of dietary metabolizable energy levels, this study was carried out. Literature on the effects of dietary metabolized energy level on the performance of geese was searched from CNKI, Wanfang, VIP, PubMed, Web of Science, and ScienceDirect databases from January 1, 2000, to December 31, 2022. A dose-response meta-analysis was performed by STATA (14.0), data were calculated by the robust error meta-regression model (REMR), and nonlinear dose-effect curves were plotted by the restricted cubic spline method (RCS). 29 papers were chosen from the 1,475 literatures that fit the criteria and were included in the dose-response meta-analysis. There were 6,079 geese included in the sample. The following production performance indices included average daily gain (ADG), average daily feed intake (ADFI), feed-to-gain ratio (F/G), dressed percentage, percentage of half-eviscerated yield, percentage of eviscerated yield, percentage of breast muscle, percentage of leg muscle and percentage of abdominal fat. The Egger test assessed publication bias, while sensitivity analysis was used to examine the heterogeneity. The verified results are consistent and reliable. The results indicated that for each group, the optimal dietary metabolizable energy level was about 13 to 13.5MJ/kg for medium-sized geese aged 0 to 4 weeks, 12 to 13MJ/kg for medium-sized geese aged above 5 weeks, 12.5 to 13MJ/kg for small-sized geese aged 0 to 4 weeks, and 13 to 13.5MJ/kg for mall-sized geese over 5 weeks of age. Future research should be conducted on related diets of large-sized geese, small-sized geese, and higher metabolizable energy levels.

We present here seven new zircon (U-Th)/He (ZHe) ages and three new zircon fission track ages (ZFT) analyzed from an age-elevation profile (Machu Picchu, Peru). ZFT data present older ages in comparison with the other thermochronological data, whereas the ZHe data interestingly present similar ages than the ones obtained with apatite (U-Th)/He (AHe). It has been proposed that He retention in zircon is linked to the damage dose, with an evolution of the closure-temperature from low values associated to low α-dose (<1016 α/g), subsequently increasing before decreasing again at very high α-dose (>1018 α /g). Studies have been focused on the He diffusion behavior at high α-dose, but little is known at low dose. We propose that the ZHe closure temperature at α-dose ranging from 0.6×1015 to 4×1016 α/g is in the range of ~60-80°C. This value is lower than the one proposed in the current damage model ZRDAAM and demonstrates that the ZHe and AHe methods could have similar closure temperatures at low α-dose (i.e. similar ages). These new data strengthen our previous geological conclusions and even highlight an about twice more important cooling rate than the one deduced from AHe and apatite fission-track data alone registered at Machu Picchu.

Background: Asthma is ranked 16th among the leading causes of years lived with disability and 28th among the leading causes of disease in the world. Metered dose inhaler remains the principal route for drug administration and it has greater advantages over systemic treatment. In routine use, however, a vast majority of patients make inhalation errors. Suboptimal inhaler technique worsens health outcomes, with poor disease control, and increases the risk of hospitalization. This study aimed to assess practice metered-dose inhalation techniques and associated factors among asthmatic patients at Debre Markos comprehensive specialized hospital, East Gojjam, Amhara region, Ethiopia. Methods: Prospective cross-sectional study was conducted from July 15 to August 30/ 2020. Data were collected through a semi-structured questioner. The data was analyzed using SPSS version 25. Associations between dependent and independent variables were assessed by using binary and multiple logistic regressions. P-values less than 0.05 were considered to be statistically significant in all cases. Results presented in tables, figures, numbers, and percentages. Result: A total of 166 patients had involved in the study, of which 52.4% were females. One hundred eleven (66.9%) of participants had good knowledge of asthma and inhalational techniques with the rest of them had poor knowledge. One hundred eight (65.1%) patients had effective practice on metered-dose inhaler use techniques. Participant's knowledge regarding asthma and meter dose inhaler and marital status has a significant association with their practice of metered-dose inhaler techniques with P-value 0.001 and 0.006 respectively. Conclusion: In this study, most participants are suffering from asthma for a long duration and they have repeated exacerbation. Around two-thirds of patients had good knowledge regarding asthma and meter dose inhaler and practice on metered-dose inhaler techniques. Participants who had poor knowledge and who were unmarried had poor practice on tech metered-dose inhaler techniques. Health education and counseling services should be consistently provided to the clients regarding the proper steps of inhalers use.

Background: Superspreading events are important drivers of the SARS-CoV-2 pandemic. By analyzing two outbreaks associated with choir rehearsals in March 2020, we demonstrate the risk of indoor, long-range (LR) transmission and singing, to help prevent similar outbreaks. Methods: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.Results: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively. WGS confirmed strain identity in both choirs and the primary case of choir 1 (transmitting presymptomatically). Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases’ emitted particles was 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (median: 89% vs. 18%, 95%CI: 80-95% vs. 6-36%). Observed AR in choir 1 (89%) was significantly higher than in choir 2 (24%). According to a risk model, first transmission in choir 1 occurred likely after 7 minutes of singing. The number of inhaled particles emitted by an infectious case, sufficient to infect 50% of exposed, was calculated to 1039-2883 particles (95%CI).Conclusions: Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. Given the potential for presymptomatic infectiousness, greatest caution is required wherever aerosols can accumulate.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

DNA vaccines are stable, safe, cost effective to produce and relatively quick and easy to manufacture. However, to date DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits and macaques, at 4 to 10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

This paper presents the results of investigations into the pyrolysis of waste polypropylene in a laboratory fixed-bed batch reactor. The experiments were designed and verified in such a way as to allow the application of the Response Surface Methodology (RSM) in the development of an empirical mathematical model that quantifies the impacts mentioned above. The influence of the mass of the raw material (50, 100 and 150 g), together with the reactor temperature (450, 475 and 500 °C) and the reaction time (45, 50 and 75 min) was examined. It has been shown that the mass of the raw material, i.e. the filling volume of the reactor, has a significant influence on the pyrolysis oil yield. This influence exceeds the influence of reactor temperature and reaction time. This was explained by observing the temperature change inside the reactor at three different spots at the bottom, middle and top of the reactor. Recorded temperature diagrams show that with greater masses of feedstock, local overheating occurs in the middle part of the reactor, which leads to overcracking of vapor products, and from there to an increased formation of non-condensable gases, i.e. reduced yield of pyrolytic oil.

In this paper, a positive answer to the open question of Fabino et al. is given, and the concept of I\c sik type set valued contractions is introduced and fixed point theorem for such contractions is established. Examples to support main theorems are given, and an application to integral inclusion is given.

This paper presents the results of investigations on the pyrolysis of tyres waste in a laboratory fixed bed batch reactor. The results regarding the influence of either the reaction temperature (425, 450, 475, and 500 °C) and the flow of the inert gas (0, 100, 300, and 500 mL/min) on products yield (referred to pyrolysis of waste tyres) are also considered and discussed. On the basis of the above mentioned findings, the most appropriate experimental conditions were selected to contribute to a higher yield of pyrolysis oil. The sample of pyrolysis oil obtained from the experiments carried out in the selected optimal conditions (reaction time 120 min, temperature 450 °C and the inert gas flow of 100 mL/min) was subjected to a calorimetric and infrared spectroscopy analysis. The results of IR spectroscopy analysis on this oil sample showed the following content in percentages (by mass): 32.59 % of aromatics, 51.06 % of paraffins and 16.35 % of naphthenes. The pyrolysis oil so obtained has a high calorific value (42 MJ/kg) and a low sulfur content (0.41 % by mass), which makes it an excellent raw material for energy production. The solid product, i.e. pyrolysis char or carbon black, has the potential to be used as an adsorbent or catalyst support after an activation process, which changes its irregular pore structure to a more voluminous one, making the overall structure more crystalline and symmetrical. Pyrolysis coal has a fairly high calorific value of 31 MJ/kg, when compared to typical solid fuels, so it can be used in energy production or as a feedstock for the gasification process.

Most of the literature on the optimization problem of transportation in supply chain networks (SCN) considered fixed costs (FC). However, in the practical applications of this problem it is important to study the effect of FC. This paper examines the impact of fixed cost increase as well as the variable cost on the optimization of a Two-Stage SCN. To do so, two mathematical models for mixed-integer nonlinear programming are developed. The first model optimizes fixed and variable costs in addition to the opening cost, whereas the second model only optimizes variable and opening costs. To evaluate the effect of considering FC on the optimization supply chain problem, four groups of instances are randomly generated, and solved using Lingo. The results of the two models are compared utilizing the average percentage deviation. In addition, sensitivity analysis is performed to determine the impact of changes in opening and variable costs on the considered optimization problem. The computational results and the sensitivity analysis show that the first model with minimized FC outperforms the second model, which does not consider the FC in minimization and FC affect the optimization.

We develop a quantitative microscopic theory of decaying Turbulence by studying the dimensional reduction of the Navier-Stokes loop equation for the velocity circulation. We have found an infinite dimensional manifold of solutions of the Navier-Stokes loop equation\cite{M93, M23PR} for the Wilson loop in decaying Turbulence in arbitrary dimension $d >2$. This family of solutions corresponds to a fractal curve in complex space $\mathbb C^d$, described by an algebraic equation between consecutive positions plus a nonlinear periodicity condition. We derive the constrained SDE for the evolution of the fractal curve at a fixed moment of physical time as a function of an auxiliary stochastic time. We expect this stochastic process to cover our fixed manifold of the solutions of the decaying Turbulence. The energy density of the fluid decays as $\mathcal E_0/t$, where $\mathcal E_0$ is an initial dissipation rate. Presumably, we have found a new phase of extreme Turbulence yet to be observed in real or numerical experiments.

The main issues of accounting reporting regarding goodwill are whether a firm’s management reliably conveys their private information about future earnings, and whether they disclose value-relevant and useful information to accounting users. In the current International Financial Reporting Standards (IFRS) regulations, the goodwill impairment test is based on management’s discretionary assessments. This study examines how goodwill impairment is reported under IFRS considering company- and industry-specific economic factors, proxies for earnings management, and macroeconomic crisis years. We extend previous research using Tobit and Logit regression, by employing a fixed-effects model. This approach is possible because of a panel data set comprising 449 of 600 active companies sampled from the STOXX Europe 600 index from 2005 to 2018. We find that goodwill impairments are largely concentrated in certain companies, industries, and years. The regression models show a significant negative correlation between companies’ return on total assets and goodwill impairments. Moreover, we discover that goodwill impairments have a significant positive correlation with goodwill intensity, debt ratio, and the proxy for reporting a one-off big bath charge. In addition, we find that the global financial crisis in 2008-2009 and the European debt crisis in 2011 differ significantly from other fiscal years

In this paper, the fixed-time stabilization problem for a class of uncertain chained system is addressed by using a novel nonsingular recursive terminal sliding mode control approach. A fixed-time controller and an adaptive law are designed to guarantee the uncertain chained form system both Lyapunov stable and fixed-time convergent within the settling time. The advantage of the controller based on the sliding mode is that the settling time does not depend on the system initial state. Furthermore, we use RBF neural network to estimate the uncertainty of the system. Finally, the simulation results demonstrate the performance of the control laws.

In the framework of a multiplicative metric space. We have discuss some Properties of convex structures in pseudo multiplicative metric space and have applied these properties toiobtain alfixed point results in complete pseudo. It would be interesting to prove some further results in such metric spaces with completeness property.

Traffic congestion is one of the foremost problems confronted by the urban and suburban tenants of today. Traffic congestion increases vehicle emissions and degrades air quality. Urban planners and policy makers have consequently been always investigating choices to alleviate traffic congestion and to enhance air quality. Teleworking is one option that has received significant consideration and has been studied in the recent past. The aim of the study is to explore the relationship between teleworking, air quality and traffic in Switzerland. The analysis relies on panel individual and household level data over the period 2002-2013. We examine five main air pollutants; the sulphur dioxide (SO₂), the ground-level ozone (O₃) the nitrogen dioxide (NO₂), the carbon monoxide (CO) and the particulate matter less than 10 microns (PM₁₀). Based on the fixed effects estimates, teleworking reduces traffic volume by 1.9 per cent. Furthermore, the reduction observed on air pollution is higher for NO₂, CO and PM₁₀ ranging between 3.3-3.7 per cent, followed by O₃ at 2.3 per cent and SO₂ at 2.1 per cent. According to instrumental variable (IV) approach and the two stage least squares (2SLS) method, the effect is higher ranging between 2.6-4.1 per cent. The respective reduction on traffic becomes 2.7 per cent. Overall, the main concluding remark of the study is that teleworking can be a promising tool for urban planning and development, focusing at the traffic volume reduction, and the air quality improvement. Additional policy implications of teleworking and its beneficial effects for the society are further discussed.

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph node or distant metastasis were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in 5 fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity.

(1) Background: “Zero-dose” (ZD) refers to a child not receiving any doses of the pentavalent (diphtheria-tetanus-pertussis-Haemophilus influenzae type b (Hib)-Hepatitis B) vaccine in the routine national immunization schedule. These children are vulnerable to vaccine-preventable diseases (VPDs), and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. The Luambo health district (HD) is one of the 26 HDs in the Kasai Central Province and has the largest number of ZD children. This study was conducted to examine the factors associated with ZD status in the Luambo HD; (2) Methods: We conducted a mixed study of children aged 12-23 months in the Luambo HD in the Kasai Central Province; (3) Results: A total of 445 children aged 12-23 months were included in the study, including 89 cases and 356 controls. Correlates of zero dose (ZD) status in children aged 12-23 months were mothers who were not receiving Antenatal Care (ANC), of not knowing any VPD, the fact of the children being born in Angola and the fact of the children being born at home. In addition, the perceptions of children’s parents influenced child immunization; (4) Conclusions: Missing ANC services during pregnancy leads to home delivery with consequences being lack of knowledge on childhood’s VPD and subsequently children not being vaccinated.

We aimed to investigate the clinical results following poor-quality embryo transfer and the parameters to foresee the prognosis. In this study, 2123 cycles that had day 3 and day 5 single-fresh embryo with a poor-quality embryo transfers and a good-quality embryo transfers were compared. The cycles according to transfer day were evaluated by conducting a subgroup analysis. The correlation between all the obtained demographic characteristics, controlled ovarian stimulation parameters and cycle results were analysed. Clinical pregnancy was established in 53 patients that underwent transfer in the poor-quality embryo group (14.9%). Of these patients, 36 had live birth (live birth rate per clinical pregnancy 67.9%). In cleavage-stage embryos, live birth rates per clinical pregnancy were higher in poor-quality blastocyst transfer. When analysing the factors affecting live births in poor-quality embryo group, as the total gonadotropin dose increases, the probability of live birth decreases, as in the probability of hCG positivity. In conclusion; although the probability of pregnant is low, when clinical pregnancy is established, there is a high chance of having a live birth after poor-quality embryo transfers. This could be regarded as an acceptable option in cycles when only poor-quality embryos were available.

This work presents patient radiation dose data for pediatric interventional cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient dose data distributions for kerma area-product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically in all weight and age bands, except the group between 1-5 years. The local DRLs were 69 Gy/cm2 (< 5 kg), 3.44 Gy/cm2 (5-<15 kg), 8.87 Gy/cm2 (15-<30 kg), 10.51 Gy/cm2 (30-<50 kg) y 22.61 Gy/cm2 (50-<80 kg), respectively. In conclusion, from comparing our results with other existing DRL values, we are similar to other centers and scope to continue optimizing the radiation dose values. This will contribute to setting national diagnostic reference levels (DRLs) for Colombia in the near future.

The papaya mealybug Paracoccus marginatus is an invasive, polyphagous pest and poses a quarantine threat to tropical and subtropical countries. Infested commodity internationally should be undergoing phytosanitary treatment, while irradiation is recommended to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-d-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy, respectively. Radiotolerance was compared using fiducial overlapping and lethal dose ratio (LDR) test, resulting in insignificant difference except for LDR test at LD90 (leading 90% mortality at 95% confidence level (CL)); the estimated dose for 99.9968% mortality at 95% CL was 176.5–185.2 Gy, which was validated in the confirmatory tests using gamma irradiation because gammy and X-rays have equal biological effect on pests. Therefore, a total of estimating 60,386 gravid females of papaya mealybug irradiated with 146.8–185.0 Gy resulted in no F1 nymphs developing. Eggs can therefore be used as an alternative to gravid females for dose-response tests; the recommended minimum dose for phytosanitary treatment of P. marginatus on infested commodity is 185 Gy, with treatment efficacy ≥ 99.9950% at 95% CL.

Angiogenesis is new blood vessel formation from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells, overexpression of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases, and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma [PRP]) im-prove tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or re-generation. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue re-pair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis other than a general one-size-fits-all statement that “PRP has angiogenic capabilities.” Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

The main aspects of material research: material synthesis, material structure, and material properties, are interrelated. Acquiring atomic structure information of electron beam sensitive materials by electron microscope, such as porous zeolites, organic-inorganic hybrid perovskites, metal-organic frameworks, is an important and challenging task. The difficulties in characterization of the structures will inevitably limit the optimization of their synthesis methods and further improve their performance. The emergence of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM), a STEM characterization technique capable of obtaining images with high signal-to-noise ratio under lower doses, has made great breakthroughs in the atomic structure characterization of these materials. This article reviews the developments and applications of iDPC-STEM in electron beam sensitive materials, and provides an outlook on its capabilities and development.

To resolve the controversial issues of UV-light-initiatedcornealcollagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen riboflavin (RF) concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), riboflavin concentration, diffusion and drops pre-operation and interoperation administration, concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square-root of light intensity, and light dose, respectively. The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

There is a lack of data comparing sugammadex with anticholinesterase for the quality of anaesthesia recovery, especially following a single bolus dose of rocuronium. Thus, we evaluated the influence of reversal with sugammadex or neostigmine on post-operative quality of recovery by using the Post-operative Quality Recovery Scale (PQRS). A total of 86 patients undergoing trans-pars plana vitrectomy (TPPV) under general anaesthesia were intubated following a single bolus dose of rocuronium (0.6 mg/kg). At the end of surgery, patients were received either neostigmine or sugammadex. The quality of recovery was assessed using the PQRS at 15 minutes and 40 minutes after surgery, and on post-operative day 1. The recovery rate in the physiological domain was higher in the sugammadex group at 15 minutes after surgery (P = 0.02). Though there were no significant differences in the overall cognitive recovery domain, patients in the sugammadex group could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the PQRS. The use of sugammadex may increase the quality of the post-operative physiological recovery at early post-operative periods compared with neostigmine use following a single bolus dose of rocuronium in patients undergoing TPPV with general anaesthesia.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

Facing the charging difficulties of free-floating shared electric vehicle and the high cost of mobile charging for single demand, this article proposes a collaborative charging planning method based on the complementary advantages of fixed charging stations and mobile charging vehicles, which can charge shared electric vehicles more efficiently and reduce the charging cost at the same time. A bi-level programming model for fixed and mobile cooperative charging is constructed. The upper level of the model is the minimization model of system charging total cost, seeking the optimal charging scheme and the number of mobile charging vehicles. The lower model is a fixed and mobile cooperative charging path planning model, which calculates the optimal routes for mobile charging vehicles and the shared electric vehicles that need to be transferred to the fixed charging station. The example results show that the cost of the proposed fixed-mobile cooperative charging scheme is reduced by 12.6% compared with the pure fixed charging scheme and 14.9% compared with the pure mobile charging scheme

Background - Mandibular flexion (MF) is a complex biomechanical phenomenon, which involves a deformation of the mandible, due mainly to the contraction of the masticatory muscles, and can have numerous clinical effects. The main aim of the current systematic review is to highlight the different factors that can increase MF, to help clinicians, identify patients to whom they should pay more attention. As a secondary outcome, we wanted to analyze the preventive measures and suitable techniques to be adopted to minimize the negative effects of this phenomenon on oral fixed rehabilitations. Methods - The review, which was carried out in accordance with the “Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) flowchart, was recorded in the “International Prospective Register of Systematic Reviews” (PROSPERO). As research questions, “Patient/Population, Intervention, Comparison and Outcomes” (PICO) questions were employed. Using the ROBINS-I technique, the risk of bias in non-randomized clinical studies was evaluated. Results - The initial electronic search identified over 1300 potential articles, of which 54 studies were included in this systematic review. Information regarding the relationship between MF and individual factors, mandibular movements, impression-taking and fixed rehabilitations were obtained. Conclusions – The studies included in this systematic review showed that MF is greater during protrusive movements, in the posterior areas of the lower jaw, and in patients with brachial facial type, greater jaw length, small gonial angle and less density, length and bone surface of the symphysis. The biomechanical effects of mandibular flexion on fixed restorations are debated. Prospective clinical and radiological observational studies should be conducted to evaluate the potential short-, medium- and long-term consequences of MF.

This study utilized panel data from 31 Chinese provinces over a period of nine years to investigate the impact of green finance on the upgrading of the agricultural industrial structure. A fixed-effect model was employed, and the findings indicate that green financing has a positive effect on the growth of China's agricultural industry. However, regional disparities exist, particularly in the uneven distribution of green financing across the eastern, central, and western regions. Moreover, it emphasizes the need to consider regional differences and tailor development strategies accordingly. To promote further development and transformation of China's agricultural industrial structure, the study recommends innovative green financial products, improved regulations and policies, and the integration of digital technologies.

The paper's main goal is to introduce a novel type of interpolative convex contraction and build up some fresh findings for it using the interpolative convex contractions' progressive approach. We have established certain conclusions using orbitally S-complete and Suzuki type contractions in F-metric spaces. My research aims to examine the fixed point method's efficacy in solving fractional differential equation with boundary conditions.

Predicting the tidal wave is essential not only to better understand hydrological cycle at the boundary between land and ocean but also to improve energy production in the coastal area. As affected by various factors such as astronomical, meteorological, and hydrological effects, predicting the tidal wave at the estuary remains uncertain. In this study, we present a novel method to improve short-term tidal wave predictions using a fixed-lag smoother based on sequential data assimilation (DA). The proposed method is implemented for the tidal wave predictions at the estuary of Nakdong River. As a result, the prediction accuracy was improved by 63.9% with DA and the calibration using the regression. Although the accuracy of DA diminished for increasing forecast lead times, the 1-hr lead forecast by DA had still 44.4% improvement over the open loop without DA. Plus, the optimal conditions for the fixed-lag smoother were analyzed in terms of the order of a smoothing function and the length of assimilation window and forecast lead time. It was suggested that the optimal DA configuration could be obtained with the 8th order polynomial as a smoothing function assimilated under 6-hr or longer past and future DA windows.

Open-cell metallic foams used as catalyst supports exhibit excellent transport properties. In this work, a unique application of metallic foam, as pelletized catalyst in a packed bed reactor, is examined. By using a wall-segment Computational Fluid Dynamics (CFD) setup, parametric analyses are carried out to investigate the influence of foam morphologies (cell size ϕ=0.45-3 mm and porosity ε=0.55-0.95) and intrinsic conductivity on flow and heat transport characteristics in a slender packed bed (N=Ddp=6.78) made of cylindrical metallic foam pellets. The transport processes have been modeled using an extended version of conventional particle-resolved CFD, i.e., flow and energy in inter-particle spaces are fully resolved, whereas porous-media model is used for the effective transport processes inside highly-porous foam pellets. Simulation inputs include the processing parameters relevant to Steam Methane Reforming (SMR), analyzed for low (Rep~100) and high (Rep~5000) flow regimes. The effect of foam morphologies on packed beds has shown that the desired requirements contradict each other, i.e., increase in cell size and porosity favor the reduction in pressure drop, however lowering the heat transfer efficiency. A design study is also conducted to find the optimum foam morphology of a cylindrical foam pellet at higher Rep~5000, which yields ϕ = 0.45, ε = 0.8. Suitable correlations to predict the friction factor and the overall heat transfer coefficient in a foam packed bed have been presented, which considers the effect of different foam morphologies over a range of particle Reynolds number, 100≤Rep≤5000.

Although CAD/CAM ceramics present a promising alternative to metal-ceramic fixed dental prostheses, little is known about their mid- and long-term clinical performance. This systematic review aims to estimate the survival and success rates and describes the underlying complication characteristics for CAD/CAM tooth-supported fixed dental prostheses (FDPs). We systematically searched MEDLINE and Web of Science to find relevant prospective studies with a follow-up of at least one year. We estimated pooled 1-, 5- and 10-year survival and success rates by combining the collected data in a Poisson regression model. Descriptive statistics were conducted to evaluate the distribution of failures and complications in the included studies. Risk of bias for the included studies was assessed with an adapted checklist for single-arm trials. Pooled estimated 1-, 5-, and 10-year survival rates ranged from 93.80% to 94.66%, 89.67% to 91.1%, and 79.33% to 82.20%, respectively. The corresponding success rates, excluding failures but including any other types of intervention, were 94.53% to 96.77%, 90.89% to 94.62%, and 81.78% to 89.25%. Secondary caries was the most frequent cause of failure, followed by chipping of the veneering. The most common cause of complication, excluding failures but requiring intervention, was chipping of the veneering. Risk of bias was generally acceptable for the included studies, with 7 studies associated with low risk of bias, 8 studies with a moderate risk of bias, and 3 studies with serious risk of bias. The current meta-analysis on CAD/CAM supported FDPs revealed satisfying survival and success rates for up to 10 years of exposure. More prospective studies focusing on long-term performance are needed to strengthen the evidence currently available in the literature.

Since smoke usually occurs before a flame arises, fire smoke detection is especially significant for early warning systems. In this paper, a DSATA(Depthwise Separability And Target Awareness) algorithm based on depthwise separability and target awareness is proposed. Existing deep learning methods with convolutional neural networks pretrained by abundant and vast datasets are always used to realize generic object recognition tasks. In the area of smoke detection, collecting large quantities of smoke data is a challenging task for small sample smoke objects. The basis is that the objects of interest can be arbitrary object classes with arbitrary forms. Thus, deep feature maps acquired by target-aware pretrained networks are used in modelling these objects of arbitrary forms to distinguish them from unpredictable and complex environments. In this paper, this scheme is introduced to deal with smoke detection. The depthwise separable method with a fixed convolution kernel replacing the training iterations can improve the speed of the algorithm to meet the enhanced requirements of real-time fire spreading for detecting speed. The experimental results demonstrate that the proposed algorithm can detect early smoke, is superior to the state-of-the-art methods in accuracy and speed, and can also realize real-time smoke detection.

The demographic profile of patients transitioning from chronic kidney disease to renal replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this population, exacerbated by the cardiovascular stress imposed by the HD procedure. The first year after transitioning to hemodialysis is associated with increased risks of hospitalization and mortality, particularly within the first 90–120 days, with greater vulnerability observed among the elderly. This review, based on data from clinics of Fresenius Medical Care Europe, Middle East, and Africa NephroCare, aims to optimize hemodialysis procedures to reduce mortality risk in stable incident and prevalent patients. It addresses critical aspects such as treatment duration, frequency, choice of dialysis membrane, dialysate composition, blood and dialysate flow rates, electrolyte composition, temperature control, target weight management, dialysis adequacy, and additional protocols, with a focus on mitigating prevalent intradialytic complications, particularly intradialytic hypotension prevention.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Purpose of Review Multipotent Mesenchymal stromal cells (MSCs) have recently risen to prominence in regenerative medicine for their powerful intrinsic properties of self-regeneration, immunomodulation, and multi-potency. They exhibited an excellent safety profile in early-phase clinical trials. Nevertheless, MSCs-based therapy suffers reduced efficacy in randomized clinical trials due to a poor understanding of their proper delivery modalities. Here, we intend to explore the current application of MSCs after tissue injuries. We specifically focus on tissue source, delivery routes, metabolic fitness, and cell dose. We further discuss potential approaches to optimize in vivo engraftment. Recent findings MSCs therapeutic effect mediates by paracrine and contact factors, which are cells' intrinsic physiological processes. The cell culture expansion process does not destroy MSCs' intrinsic properties. In vivo persistence of administered MSCs determines their therapeutic potency. Cell viability, fitness, immune match, and delivery route meticulously regulate their in vivo persistency. Different genetic or chemical modification strategies are currently applied to extend their in vivo lifespan and boost their pharmaceutical effect. Summary Improving the in vivo persistence of implanted MSCs could facilitate its clinical translation. This review highlights the pros and cons of different MSCs’ delivery strategies used in clinical or preclinical studies, emphasizing various modification approaches. These can promote prolonged graft cell survival.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Photon-counting Computed Tomography (PCCT) is a promising cardiovascular-imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in vascular imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of vascular conditions. Of the 13 records selected in the initial search, 7 articles were included in the present review: 6 cohort studies and 1 case report. This review synthesized the available literature on PCCT in vascular imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.