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

Nowadays the freedom to make choices is considered of vital importance for decision-makers. Researchers investigating the psychological effects of choice provided empirical evidence about the many advantages of choice (i.e., increased intrinsic motivation, greater perception of self-determination, better performance, and greater life satisfaction). However, more recent studies demonstrated the downsides of choice. When the decision task difficulty exceeds the natural cognitive resources of human mind, the possibility to choose becomes more a source of unhappiness and dissatisfaction than an opportunity for a greater well-being. We here discuss in a detailed fashion the main findings of research in psychology and consumer behavior showing the bright sides and the downsides of choice.

Sustainable food consumption has attracted a widespread attention during last decades by scholars, policy makers and consumers. In line with this, farmers’ markets (FMs) have the potential to encourage sustainable agricultural production and consumption. By reducing the number of actors and distances along the food chain, these alternative food systems foster the reconnection between farmers and consumers and contribute to different social, economic and environmental sustainable goals. This paper provides insights on the role of consumers' sustainability concerns related to their motivation for shopping at FMs. By means of a choice experiment, we analyze the determinants of consumers’ WTP for buying apples at FMs. We are particularly interested in understanding how attitudes towards the three sustainability dimensions are related to consumer preferences in this context. We find that consumer attitudes towards direct contact with producers, contributing to farmers’ income, and environmental benefits can be directly related to product characteristics that are specific to FMs.

Noni juice is a globally popular health beverage that originates from the tropics. Traditional Tahitian healers believe the noni plant to be useful for a wide range of maladies, and noni juice consumers throughout the world have similar perceptions. Nevertheless, human clinical trials are necessary for an understanding of what the health benefits of noni juice truly are. A review of published human intervention studies suggest that noni juice may provide protection against tobacco smoke-induced DNA damage, blood lipid and homocysteine elevation, and systemic inflammation. Human interventions studies also suggest that noni juice may improve joint health, increase physical endurance, increase immune activity, inhibit glycation of proteins, aid weight management, help maintain bone health in women, help maintain normal blood pressure, and improve gum health. Further, these studies point to noni juice possessing notable antioxidant activity, more so than the other fruit juices that served as placebos. It is this antioxidant effect, and its interaction with the immune system and inflammation pathways, that may account for many of the observed health benefits of noni juice. However, the existing evidence does have some limitations in its application to noni juice products in general as all the peer-reviewed human interventions studies to-date have involved only one source of French Polynesian noni juice. Geographical factors and variations in processing methods are known to produce commercial noni juice products with divergent phytochemical and nutrient compositions. Therefore, other sources of noni products may have different toxicological and pharmacological profiles.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

This paper explores multiple perspectives and proofs regarding the validity of what is considered to be one of the – if not THE - most controversial proofs in the field of mathematics, historical and contemporary applications alike. We consider the various explanations and equivalents of the axiom along with the more widely receptive alternatives. Furthermore, we review the resistance the axiom has encountered in various fields and its potential use in the research and expansion of said fields.

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

Given the Income enabling nature of education as stipulated by human capital theory, it can be postulated that “ceteris paribus”, households with formally educated heads experience less food insecurity and monetary poverty than those with uneducated heads. We test this claim in the case of Burkina Faso, using the 2014 National Survey on Households Living Conditions, along with semi-parametric modeling techniques. In its design the study uses households “willingness and ability” to spend annually on food consumption a per-capita amount above the food poverty line of 102,040 CFA Franc to characterize “household food security”, and households “unwillingness or inability” to spend above the overall poverty line of 153,530 CFA Franc to characterize “monetary poverty”. In addition, the study relies not only on single equation multivariate probit and logit specifications, but also on both fully parametric and semi-parametric bivariate probit representations of food insecurity and monetary poverty. The results show that relaxing the linearity and independence assumptions through joint semi-parametric bivariate modeling captures better the true effects of heads of households’ educational attainment on households' food insecurity and monetary poverty. In fact, compared to households headed by someone with no education, those headed by someone with a primary, secondary or higher education are respectively 19.8% , 49.7% and 118.9% less likely to experience food insecurity, and respectively 40.1%, 77.0% and 172.3% less likely to experience monetary poverty in Burkina Faso. In addition, the experience of food insecurity and monetary poverty are highly correlated at 92.7%, suggesting that educational policies that alleviate poverty in Burkina Faso should also impact positively food security in the country.

Machine reading comprehension aims to teach machines to understand a text like a human, and is a new challenging direction in Artificial Intelligence. Datasets play an important role while describing or building an algorithm for machine reading comprehension. The type of answers we required from developed algorithm depends on datasets.The datasets are classified into two types, namely datasets with extractive answers and datasets with descriptive answers. This article summarize both datasets with an example of each type to get better insight of datasets in machine reading comprehension and which datasets to use depending the requirements.

Development of early math skills is linked to future success in mathematics and other academics. Educational videogames have been shown to promote academic achievement; however, few rigorous studies have evaluated the use of educational videogames in supporting math development, especially in early primary education. In the current study, an open-label randomized controlled trial was conducted involving 134 first grade students to determine, using standardized assessments, the impact of the educational mathematics tablet-based videogame, Knowledge Battle, on math scores and self-competency. Overall, Knowledge Battle did improve math skills in participants who played the game. Among those with lower pre-game math skills, the Knowledge Battle group’s mean math score increased more than the control group’s mean math score (9.7 vs. 6.0; p=0.02). There was no association between perceived sense of self-competency and total math score (p=0.8141). However, players who had a higher sense of self-competency were more likely to enjoy playing the game. In conclusion, our findings suggest that Knowledge Battle was an acceptable and enjoyable educational mathematical videogame for first grade students, and may be most impactful for those with low math skills.

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

The purpose of this study is to investigate the effect of academic advising on changing or maintaining majors in university degrees. It is also a goal of the study to determine which semester of the course study is most likely or less likely witness the change of major and whether advising contributes to that change. Through this correlational study, the researchers explored students’ perceptions about the academic advising they received and the relationship of its absence on students’ major change. The participants were 1725 undergraduate students from all year levels. One survey is used to collect the data for this study: Influences on Choice of Major Survey. Based on the findings, it is found that university advisors have a very poor effect on students' decisions to select their majors as 45.6% of the 1725 participants indicate NO influence of advising in their survey answers. Whereas career advancement opportunities, students' interests, and job opportunities indicate a strong effect on their majors’ selections as they score the highest means of 3.76, 3.73, 3.64 respectively. In addition, findings show that students are most likely changing their majors in their second year and specifically in the second semester. Second year major change scored 36.9% in the second semester and 30.9% in the first semester. More importantly, results indicate that there is a positive significant correlation between college advisor and change major in the second year (p = 0.000). It is to researchers understanding based on the findings that when students receive enough academic advising in the first year of study and continues steadily to the next year, the possibilities of students changing their majors decreases greatly.

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

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

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

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

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

This study aims to assess food security status of rural, peri-urban and urban households and role of socio-economic factors in ensuring food security. A survey was conducted to collect primary (quantitative) data from 630 respondents using proportionate sampling technique from Punjab, Pakistan. Cronbach’s Alpha reveals stability (>0.75) of data scale items. Using Dietary Intake Assessment (DIA), findings reveal urban households as highly food-secure whereas rural household as most vulnerable to food security at 2450kcal/day per person. Study indicates food price increase as the leading factor in preventing food security among households. Contrary, study identifies risk factors associated to food quality under the abundant availability and access as the new dimension to household food insecurity. Further, results of binary logit model show that socio-economic factors such as monthly income, total number of earners, education of household head and access to market are positively related with food security status whereas, social isolation, volatility in food prices and risk factors in food quality are negatively related with household food security. Therefore, study proposes educational orientation and entrepreneurial development as sustainable solution to ensure food security among masses. Besides, further country level researches are advised to deep delve the mounting menace of food security.

Choice poetics is a formalist framework that seeks to capture the impacts choices have on player experiences within narrative games. Developed in part to support algorithmic generation of narrative choices, the theory includes a detailed analytical framework for understanding the impressions choice structures make by analyzing the relationships between options, outcomes, and player goals. The theory also emphasizes the need to account for players’ various modes of engagement, which vary both during play and between players. In this work, we illustrate the non-computational application of choice poetics to the analysis of three different choices, in order to further develop the theory and make it more accessible to others. We focus first on analyzing so-called false choices in the game “Mass Effect”, and show how they actually provide meaningfully different outcomes for players who are utilizing certain modes of engagement. Second, we use choice poetics to examine the central repeated choice in “Undertale”, and show how it can be used to contrast two different player types that will approach a choice differently. Finally, we give an example of fine-grained analysis using a choice from the game “Papers Please”, which breaks down options and their outcomes to illustrate how the choice pushes players towards complicity via the introduction of uncertainty. Through all of these examples, we hope to show the usefulness of choice poetics as a framework for understanding narrative choices, and to demonstrate concretely how one could productively apply it to choices ‘in the wild’.

The study of eco-evolutionary feedbacks is in clear recent expansion. However, most studies concern predator-prey and host-parasite interactions, while the analysis of eco-evolutionary feedbacks involving sexual interactions is lagging behind. This is at odds with the potential of these interactions to engage in such processes. Indeed, there is now ample evidence that sexual selection is affected by ecological change. There is also evidence that sexual selection traits evolve rapidly, which may modify the ecological context of species, and thus the selection pressures they will be exposed to. Here, we first set a clear distinction between processes in which ecology drives evolution and those in which the contemporary evolution of populations may change their ecology, depending on which traits act as drivers and objects of change. We then review evidence for these processes and discuss examples of closed eco-evolutionary feedbacks in an attempt to understand how we can tear this loop apart. We suggest that a better understanding of eco-evolutionary feedbacks of sexual selection may help us understand the effects of sexual selection on the rate of adaptation, speciation, and extinction, and thus foster future research in this area.

This study used double-bounded dichotomous-choice to estimate and analyze the factors affecting households’ willingness to pay (WTP) for water quality improvement. This study notes that households with higher income, living near polluted water source, using tap water instead of natural water, who are handicraft producers, and who have more members are willing to pay more. However, households who rarely hear about environmental pollution issues and who are offered a higher bid are more likely to refuse to pay. Solutions to improve water quality are suggested such as to raise people's awareness through communication channels and social organizations; to increase income associated with environmental protection policies; to construct wastewater treatment plants; to encourage the relocation of production establishments to industrial parks and industrial complexes; to put regulations on collection, payment and sanctions in case of not declaring and paying fees into village conventions; to promulgate circulars, and bylaws to concretize and simplify regulations and policies of the Government, Ministry of Natural Resources and Environment.

This article takes an approach to explaining the behavioral manifestations of the decision making in US companies’ offer of health insurance that is grounded not only on their cost minimizing behavior, but also in a humanness dimension based on the African concept of Ubuntu. In this way, we define an Ubuntu based Random Utility modeling framework, describing the choice process as a tripartite decision making, and implemented using a nationally representative random sample of 1,061 American companies from the Dunn and Bradstreet Business data, supplied by Survey Sampling International to the Associated Press-NORC Center for Public Affairs Research. The results from the three sequentially implemented specifications showed that the relationship between management culture and health plan offering strategy is dependent on other relevant co-variates, which when left out, leads to the problem of omitted variables bias. However, when all variables are included but assumed to enter the relationship exogenously, this results in management culture not having any statistically significant effect on companies' decisions about scope of health plan offering. When the exogeneity assumption is relaxed through a recursively Bivariate Probit model, the system of two equations produces a highly significant management culture effect. In fact, in this later case we see that companies with groups and formal committee management culture are 1.58 times less likely to choose a multiple plan strategy over a single plan strategy, hence failing to show the more wholesome plan offering that would theoretically prevail under Ubuntu style management.

Background. Restoring large defects with proximal caries extending below the cemento-enamel junction and cavity margins located beneath the gingival tissues represents a very common clinical situation. The aim of this article is to propose a clinical classification of the localization subgingival margins of cavity.Material and methods. Diagnosis is carried out by periodontal probe perpendicular to the long axis of the tooth in the deepest point of the cavity’s margin. To describe the localization subgingival margins of cavity we use exponent which value is equal to the distance (integer number expressed in millimeters) of the level of epithelial attachment to the margin of the cavity. Three periodontal examiners, with >10 years of periodontal practice, were required to attend a calibration session aimed at the validation of the proposed classification. Results. The intrarater and interrater agreement among the localization subgingival margins of cavity: for intrarater agreement ranged from 0.74 to 0.95 (almost perfect agreement), whereas interrater agreement ranged from 0.26 to 0.59 (moderate agreement).Conclusions. The classification the localization subgingival margins of cavity is useful for reaching a more precise diagnosis.

: Background: Overweight and obesity are major risk factors for many chronic diseases, and weight-loss interventions often include systematic exercising and nutritional supplements. The purpose of this study was to determine the independent/synergistic effects of Spirulina maxima supplementation (6-week, 4.5 g/day) and a systematic physical exercise program (6 weeks/ 2 times) on body composition and cardiorespiratory fitness of overweight and obese subjects. Methods: 27 overweight and 25 obese sedentary male subjects were assigned to four interventions through a randomized double-blind, crossover controlled trial: Physical exercise program with (SE) or without (Ex) Spirulina maxima or no-exercise program with (Sm) and without (C) Spirulina maxima. Body composition and cardiorespiratory fitness parameters were taken during a maximal intensity test. Results: As compared to C group, SE, Sm and Ex groups reduced (p < 0.05) their body fat percentage while improving their maximal oxygen uptake (VO₂max; r = −0.40), being obese subjects more benefited. Weight loss, time to reach fatigue and onset of blood lactate accumulation were improved in both Spirulina maxima supplemented groups, regardless the subjects’ body composition. Conclusions: Spirulina maxima supplementation synergistically improves the effects of systematic exercise in body composition and cardiorespiratory fitness parameters in overweight but mostly in obese adults.

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

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

Energy system optimization models (ESOM) are widely used to inform about energy transition strategies. The heterogeneity of consumers, especially in the heat sector, is rarely considered in these model types. Integrating consumer heterogeneity and behavioral factors into ESOMs may generate new insights for energy policy. In this study a literature review was conducted, identifying empirical data on consumer behavior for adopting residential heating systems. This data was integrated into an ESOM for the German heat sector, combining established methods for integrating consumer heterogeneity and a novel approach for calculating indirect costs, representing behavioral factors. The incorporation of consumer choice leads to a higher diversity in technology market shares in a business as usual and an ambitious measures scenario. Especially, the future role of log wood technologies in the private household sector may have been underestimated in previous studies and should be discussed, when designing policies. Still, these findings need to be handled with care, since the empirical data basis and the methodological basis is limited.

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

: E-commerce sales surge represents a huge challenge for urban freight transport. Parcel lockers constitute a valid solution for addressing the challenges home deliveries imply. In fact, eliminating courier-consumer contact (also relevant for health-related issues, as made evident by COVID19 pandemic) and delivering in few predefined places might help coping with missed deliveries substantially. Furthermore, this option enables consolidated shipping and reducing delivery trip costs. This paper analyses and compares consumers’ preferences for alternative collection strategies. It investigates home delivery vs parcel locker use and forecasts their future market shares. This is performed based on both customers’ socio-economic variables and attributes characterising these alternative logistic fulfilment strategies. The case study considered rests upon a stated preference survey deployed in the city of Rome. The investigation specifically targets young people (i.e., population under 30 years) since they represent early adopters. Discrete choice models allow both quantifying the monetary value of parcel lockers attributes (i.e., willingness to pay measures) and estimating the potential demand for this innovative delivery scheme. Results show that distance and accessibility are the main choice determinants. Furthermore, there is an overall high propensity to adopt parcel lockers. This research can support policymakers when implementing such solutions.

In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.

Lichen secondary metabolites are generally considered as repellent compounds for lichen feeders. Nevertheless, if the only food available consists in lichens rich in secondary metabolites, lichenophages such as Notodiscus hookeri, a gastropod native from the Possession Island, seem able to implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites appears to play a key role in their feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behavior of Notodiscus hookeri fed exclusively with Usnea taylori, a lichen rich in usnic acid and arabitol. Snail feeding choice experiments with intact lichens vs acetone-rinsed lichens were carried out to study the influence of secondary metabolites. Simultaneously, usnic acid and arabitol were quantified and localized within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution induce preferential snail grazing. Then, no-choice feeding experiments were devised using usnic acid and arabitol embedded in artificial diet, separately or together. This case study demonstrated that the nutritional activity of N. hookerii was governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolites (usnic acid).

The objective of this study was to review the study design and preliminary results of the Recovery trial and analyze the implementability of the Recovery trial by comparing it with the European Discovery trial.Method: The study design of the Recovery trial in the latest version of protocol was described and deeply analyzed to address the issue of implementation of the trial. A comparative analysis of study design and implementation between the UK Recovery trial and the European Discovery trial was conducted following the description.Results: The Recovery trial is a pragmatic, randomized, controlled, adaptive, open-label clinical trial. The study design of the Recovery trial was reported in the ISRCTN registry, the EU Clinical Trials Register and the U.S. National Library of Medicine ClinicalTrials.gov registry. Initially published on the 13^th March 2020, the study protocol of the Recovery trial has been updated five times at the time of this writing. More than 11,000 patients have been enrolled and 80% have completed the follow-up. Thousands of health care professionals at 175 Trusts in the UK have been involved. Conclusion: The Recovery trial applies a study design to address the issue of implementation in the context of the COVID-19 pandemic and emergency. It was conceptually pragmatic with a clear vision to address the top priority: the control of mortality and rational use of scarce resources. By contrast, the Discovery trial was designed as an intellectual exercise and consequently failed to address the issue of implementation in emergency.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

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

Meta-analysis of plant sterol supplement studies suggests an 8% lowering of LDL cholesterol for 2 to 2.5g/day of plant sterols. Cereal foods have been rarely tested and one study showed a lower LDL lowering of 5.4% with 1.6g of plant sterol in breakfast cereal. We aimed to test a breakfast wheat biscuit with 2g of plant sterols in a single serve of two wholegrain wheat breakfast cereal biscuits. Fifty volunteers with a total cholesterol of >5.5mmol/L were recruited for a randomised crossover study with two 4-week periods with no washout of which 45 successfully completed the study. After exclusion of four outliers the difference in LDL cholesterol between standard wholegrain wheat breakfast cereal biscuit and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L or 5.6% (P=0.001) with a 95% confidence interval of 2.4-8.9%. Men and daily cereal consumers had greater responses 9.8% vs 3.6% and 7.2% vs 3.8% respectively (P<0.05). The LDL lowering effect of 2g of plant sterol enriched from one serve of wholegrain wheat breakfast cereal biscuit was not significantly different from other food products delivering 2-2.5g of plant sterols daily. Regular cereal consumers have a better response.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

Selenium and iodine are essential micronutrients for humans. They are often deficient in food supply due to low phytoavailable concentrations in soil. Agronomic biofortification of food crops is one approach to overcome micronutrient malnutrition. This study focused on German consumers’ willingness to purchase selenium- and/or iodine-biofortified apples. For this purpose, an online survey was carried out. In this context, consumers were asked to choose their most preferred apple product from a set card of product alternatives (Discrete Choice Experiment). The multinomial logit model results demonstrated that German consumers’ have a preference in particular for iodine-biofortified apples. Furthermore, apple choice was mainly influenced by price, health claims, and plastic-free packaging material. Viewed individually, selenium did not exert an effect on product choice whereas positive interactions between both micronutrients exist.

Pharmacological treatment is not very effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in the use of the multimodal analgesic approach. We performed a new, independent review to assess whether more evidence and of better-quality has become available since the last systematic review. We evaluated the efficacy, tolerability, and safety of double-blinded, randomized, controlled trials involving only adult participants and comparing combination therapy (CT: ≥ 2 drugs) to a placebo and/or at least one other comparator with an NP indication. The primary outcome assessed was the proportion of participants reporting ≥50% pain reductions from baseline. The secondary outcome assessed was the proportion of drop-outs due to treatment-emergent adverse events. After removing duplicates, 2323 citations were screened, with 164 articles assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only five lasted for at least 12 weeks and only six complied with the required data for complete analysis. CT has been adopted for years without robust evidence. Efforts have been made to achieve better-quality evidence, but the quality has not improved over the years. In this regard, guidelines for NP should attempt to make recommendations about CT research, prioritizing which combinations to analyze.

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

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccines in pipeline to prevent it but a systematic review on immunogenicity and safety of vaccine is lacking. Methods: This systematic review of RSV vaccine clinical trials was undertaken using 4 databases. Searches were conducted using both controlled vocabulary terms such as ‘Respiratory Syncytial Virus, Human’, ‘Respiratory Syncytial Virus Infections’, ‘Respiratory Syncytial Virus Vaccines’, ‘Immunization’, ‘Immunization Programs’ and ‘Vaccines’ and corresponding text word terms. The searches for published papers were limited to clinical trials published from January 2000 to August 6th, 2018. RSV infection case was defined as RSV associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically-confirmed test (Western Blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results: Of 4395 publications, 24 were included and data were extracted covering 4 major types of RSV vaccine candidates, these being live-attenuated/chimeric (n=9), recombinant-vector (n=10), subunit (n=1) and nanoparticle vaccines (n=4). For RSV infection cases, 7 trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. Conclusion: LID ∆M2-2, MEDI M2-2, and RSVcps2 (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate was considered as a potential effective vaccine. Although no promising vaccine was identified from pregnant-women test, RSV F-024 subunit vaccine candidate and an RSV F nanoparticle vaccine showed encouraging results in healthy non-pregnant women.

The present study explored the effects of a Second-generation mindfulness-based intervention known as Flow Meditation (Meditación-Fluir) in the improvement of life habits. A sample of university students (n = 51) in Spain were randomly assigned to a seven-week mindfulness treatment or a waiting list control group. Results showed that compared to the control group, individuals in the mindfulness group demonstrated significant improvements across all outcome measures, including healthy eating habits (balanced diet, intake rate, snacking between meals, decrease in consumption by emotional states negative, increased consumption by negative emotional states, amount of consumption, meal times, consumption of low-fat products), tobacco, alcohol and cannabis consumption, and resting habits. There were differences between males and females in some of these variables and a better effect of the treatment was evident in the females of the experimental group as compared to males. The Flow Meditation program shows promise for fostering healthy life habits, thus decreasing behaviors related to maladaptive eating, tobacco, alcohol and drug consumption, as well as negative resting habits, in university students. This mindfulness program can significantly contribute in the treatment of eating disorders and addictions, wherein negative emotional states and impulsivity are central features of the condition.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Pneumonia kills over two million children under-age of five every year. Oral amoxicillin was recommended by WHO as the first drug of choice for treatment of non-severe pneumonia. The study aimed to determine the clinical failure rate of amoxycillin for the treatment of childhood non-severe pneumonia at Primary Health Care Centers (PHCCs). A randomized controlled multicenter-trial study was conducted in Sana’a. IMCI strategy was used to enrollments the cases where randomly allocated to receive amoxicillin or co-trimoxazole orally for five days. Multivariate logistic regression was used for identified risk factors associated with clinical failure. A total of 254 children were enrolled, of whom 128 cases were treated with amoxicillin while 126 with co-trimoxazole. The clinical failure for amoxicillin was significantly more than co-trimoxazole (30% vs 10%) p value > 0.001. the most risk factor which significantly associated to amoxicillin failure were pre-infection in the last 6 months, while abnormal CBC and literate mothers were associated with clinical failure of co-trimoxazole (p value > 0.05). The use of co-trimoxazole as an alternative to amoxicillin for the treatment of non-severe pneumonia in the PHCCs and conducting further studies to determine the appropriate antibiotic as the first line of defense are recommended.

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

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

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

Attitudes and behaviours towards the natural environment have been extensively studied in certain cultural settings during the last 40 years. In education, the teacher's ability to grasp the fundamentals of an academic subject may define his or her own attitudes towards that discipline; certainly the reverse is also valid. The correlations between affective and cognitive domains appear to play a significant role in teaching-learning dynamics. In this study we seek to assess whether the affective posture towards school sciences of a cohort of teachers in rural communities shows an association with their cognitive competence in the disciplines. The results of this study provide evidence that there is a statistically significant correlation between the cognitive and affective domains for in-service teachers. The affective domain, therefore, could serve as a predictor for cognitive competency and self-efficacy expectancies with respect to both content and career fulfilment.

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

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

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

Aim: The overall aim of the study was to assess the reasons and experiences of participants involved in Antibody Mediated Prevention (AMP) HIV prevention clinical trial at University of North Carolina (UNC) Project, Lilongwe, Malawi. We determined the participants’ reasons for participating in HIV Prevention clinical trials; and the experiences of participants in HIV Prevention clinical trials. Methods: We adopted the qualitative cross-sectional study method. Data were collected using in-depth interviews (IDIs). Purposive sampling was used to select 12 study participants who consented to take part in the study. All participants were the ones taking part in the AMP HIV prevention study at the UNC Project. Data analysis was done concurrently with data collection using content analysis. Results: Individuals were motivated to participate in HIV research due to a range of perceived benefits. These included personal, health, and financial benefits. Participants' research experiences and their continued participation in HIV research were influenced by the research clinic context and the nature of their interactions with research staff. Conclusion: When the clinical trial study participants’ expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends

The city of Lisbon, has any other capital of a European country, has a large number of issues while managing the waste and recycling containers spread throughout the city. This document presents the results of a study promoted by the Lisbon City Council for trialing LPWAN technology on the waste management vertical under the Lisbon Smart City initiative. Current waste management is done using GSM sensors, and the aim is to use LPWAN to reduce the costs, improve range and reduce provisioning times when changing the communications provider. After an initial study, LoRa was selected as the LPWAN of choice for the trials. The study is composed of multiple use cases at different distances, types of recycling waste containers, placements (underground and surface) and different kinds of waste level measurement LoRa sensors, deployed in order to assess the impact of the different use cases on the LoRa sensor usage. The results shown that the underground waste containers present the most difficult challenge, where the container itself imposes attenuation levels of 26dB on the link budget. The results promoted the deployment of a city wide LoRa network available to all departments inside the Lisbon City Council, and considering the network capacity the network, the network is also available to citizens to be used freely.

Model selection and model averaging have been the popular approaches in handling modelling uncertainties. Fan and Li(2006) laid out a unified frame work for variable selection via penalized likelihood. The tuning parameter selection is vital in the optimization problem for the penalized estimators in achieving consistent selection and optimal estimation. Since the OLSpost-LASSO estimator by Belloni and Chernozhukov (2013), few studies have focused on the finite sample performances of the class of OLS post-penalty estimators with the tuning parameter choice determined by different tuning parameter selection approaches. We aim to supplement the existing model selection literature by studying such a class of OLS post-selection estimators. Inspired by the Shrinkage Averaging Estimator (SAE) by Schomaker(2012) and the Mallows Model Averaging (MMA) criterion by Hansen (2007), we further propose a Shrinkage Mallows Model Averaging (SMMA) estimator for averaging high dimensional sparse models. Based on the Monte Carlo design by Wang et al. (2009) which features an expanding sparse parameter space as the sample size increases, our Monte Carlo design further considers the effect of the effective sample size and the degree of model sparsity on the finite sample performances of model selection and model averaging estimators. From our data examples, we find that the OLS post-SCAD(BIC) estimator in finite sample outperforms most of the current penalized least squares estimators as long as the number of parameters does not exceed the sample size. In addition, the SMMA performs better given sparser models. This supports the use of the SMMA estimator when averaging high dimensional sparse models.

Interpretation of increased gain in the bovine animals is difficult to be validated due to inherent genetic variation to meet their requirement for energy and protein, and those may relate to the bull species, e.g., Thai swamp buffalo. Therein, the study aimed at investigating and predicting protein requirement systems, with providing abundant energy intake 2.20 Mcal/kg DM for maintenance and growth of Thai swamp buffaloes using the comparative prolonged feeding trial for 90 days. Sixteen bull Thai swamp buffaloes at the initial (Age: 18-24 months; BW: 233 ± 25.0 kg) were as-signed into four treatment groups, four buffaloes each, fed 5.42, 6.96, 8.94, and 10.71% DM crude protein (CP). CP intake, BW, and physiological fluid were determined. The net CP requirements for maintenance and growth of Thai swamp buffaloes were 5.41 g CP/kg W0.75 and 0.46 g CP/g average daily gain (ADG), respectively. Our results indicated that CP requirement increases, when BW increases. An increased dietary CP resulted in an increased number at blood urine nitrogen (N), N absorption, total volatile fatty acid, urinary purine derivative, and the microbial N. Notably, the net CP requirement for growth of Thai swamp buffalo was higher than it reported in NRC, but the maintenance was lower.

Over the past decade, Thailand has experienced a rapid increase in its elderly population. Many unfavorable health outcomes among elderly people are associated with nutrition. Nutrition in elderly people is affected by physical, mental, and social factors. This study explored the food choices and dietary practices among community-dwelling elderly people in Thailand from the perspective of both caregivers and the elderly people themselves. Six focus group discussions and six semi-structured interviews were conducted in the Samut Sakhon Province of Thailand. A combination of deductive and inductive thematic analyses was adopted, and the results show that physical and mental factors and societal factors are important determinants of food choices. Moreover, a changing food environment and economic factors were found to affect food choices. Issues of trust in food safety and food markets were highlighted as growing issues. Therefore, fostering healthy food choice interventions that consider both environmental and societal aspects is necessary.

Enhance®Fitness (EF) is an evidence-based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF in rural, community-dwelling older adults with symptomatic knee OA. A single arm pilot trial of remotely delivered EF classes was conducted. Videoconferencing was used to livestream the instructor-led, 1-hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post-intervention. A total of 15 participants were enrolled with a median age of 70 years (interquartile range [IQR]: 67-75) and 14 (93%) were women. Median EF class attendance rate was 91% (IQR: 85-94%). Knee pain, as measured by the Knee injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to 12-week endpoint (mean difference=-11.4 [95% CI:-20.9, -2.0); P=0.02). In addition, participants’ self-reported knee function improved significantly (mean difference in KOOS Function score=-11.8 [95% CI:-18.4, -5.2]; P&lt;0.01) as well as their physical capacity (mean difference in Timed Up and Go test time=1.8 seconds [95% CI: 0.2, 3.4]; P=0.03). All participants (100%) were very satisfied with remotely delivered EF classes and there were no serious adverse events. Findings from this pilot trial indicate that remotely delivered EF is feasible and acceptable in rural older adults with knee OA.

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

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double-blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and acceptability of the intervention in preparation for a future 8-week RCT which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n=10) and non-depressed (n=6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to diet allocation and study hypotheses. Health questionnaires were completed before and after the intervention, and, throughout the study, questionnaires assessed ratings of liking and sensory properties of the meals, adherence, and open-ended feedback. In the ND group, 75% of participants consumed no non-study foods, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

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

Very hot (> 65 °C) beverages such as espresso were evaluated by the International Agency for Research on Cancer (IARC) as probably carcinogenic to humans. For this reason, research into lowering beverage temperature without compromising its quality or taste is important. For espresso, one obvious possibility consists in lowering the brewing temperature. In two sensory trials using ISO 4120:2004 triangle test methodology, brewing temperatures of 80°C vs. 128°C and 80° vs. 93°C were compared. From the tested levels, espresso brewed at the lowest temperature had the highest acceptance. However, most tasters were unable to distinguish between 80°C and 93°C. The results of these pilot experiments proof the possibility to decrease the health hazard of very hot beverages by lower brewing temperatures.

The manipulation of participant allocation in randomized controlled trials to achieve equal groups sizes may introduce allocation bias potentially leading to larger treatment effect estimates. This study aimed to estimate the proportion of nursing trials that have precisely equal group sizes and examine if there was an association with trial outcome. Data were extracted from a sample of 148 randomized controlled trials published in nursing science journals in 2017. One hundred trials (68%) had precisely equal group sizes. Respectively, a positive outcome was reported in 70% and 58% of trials with equal/unequal groups. Trials from Asia were more likely to have equal group sizes than those from the rest of the world. Most trials reported a sample size calculation (n=105, 71%). In a third of trials (n=36, 34%), the number of participants recruited precisely matched the requirement of the sample size calculation; this was significantly more common in studies with equal group sizes. The high number of nursing trials with equal groups may suggest nurses con-ducting clinical trials are manipulating participant allocation to ensure equal group size increasing the risk of bias.

Purpose: To explore the influence of education and other factors on an athlete’s decision to return to sport post-concussion injury, and whether general risk-taking tendencies are related to return to sport post-concussion decisions in these athletes. Participants and Methods: A self-administered electronic survey was designed to examine their decision-making process when faced with scenario-based questions regarding returning to sport post-concussion injury. Students from the Health Sciences and Medicine Faculty at Bond University were invited to participate. Participants were allocated to a concussion education or non-education group prior to commencement of questionnaire via the random generator on Qualtrics software function. The risk propensity scale was used to assess the risk aversion of each participant. Results: Sixteen respondents were randomized evenly to education and non-education groups. Seven (43.8%) had previously received concussion education training prior to completing the questionnaire, with one (14%) choosing to return to sport in the scenario-based questions. The education group reported two (25%) respondents return to sport, while three (75%) respondents out of four returned to sport with no education or previous concussion training. Influential factors that impacted the decision whether to return to sport or not included: game importance, concussion severity and symptoms, and various internal and external factors. Finally, there was a divergence in results from the risk propensity scale when deciding to return to sport and general risk-taking propensities. Conclusion: This study identified several influential factors including game importance, concussion severity and symptoms which play a significant role in the return to sport decisions post-concussion injury.

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

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

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

Background: COVID-19 has impacted Indian engineering institutions (EIs) enormously. It has tightened its knot around EIs that forced their previous half-shut shades completely down to prevent the risk of spreading COVID-19. In such a situation, fetching new enrollments on EI campuses is a difficult and challenging task, as students’ behavior and family preferences have changed drastically due to mental stress and emotions attached to them. Historically, during crisis situations, institutions have struggled to return to the normal track. Consequently, it becomes a prerequisite to examine the choice characteristics influencing the selection of EI during the COVID-19 pandemic to make it ‘normal’ for ‘new’ enrollments. The purpose of this study is to critically examine choice characteristics that affect students’ choice for EI and consequently to explore relationships between institutions’ characteristics and the suitability of EI during the COVID-19 pandemic across students’ characteristics. Quantitative research, conducted through a self-reported survey composed of a closed-ended structured questionnaire, was purposefully incorporated into the students who recently were enrolled in EIs (batch years 2020-2021) belonging to the North Maharashtra region of India. Results:The findings of this study revealed dissimilarities across students’ characteristics regarding the suitability of EIs under pandemic conditions. Regression analysis revealed that EI characteristics such as proximity, image and reputation, quality education and curriculum delivery have significantly contributed to suitability under COVID-19. At the micro level, multiple relationships were noted between EI characteristics and the suitability of EI under the pandemic across students’ characteristics. Conclusion:Bringing ‘normality’ to ‘new’ enrollments totally depends on EI’s resilience in meeting the needs of diversity in the COVID-19 pandemic situation, which repositions themselves to govern student-centric strategies instituted for the overall suitability of EI under pandemic conditions. The study has successfully demonstrated how choice characteristics can be executed to regulate the ‘suitability’ of EI under the COVID-19 pandemic for the inclusion of diversity. It is useful for policy makers and academicians to reposition EIs that fetch diversity during the pandemic. This study is the first to provide insights into the performance of choice characteristics and their relationship with the suitability of EIs under a pandemic and can be a yardstick in administering new enrollments.

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low levels of a constant current via scalp electrodes to specifically targeted areas of the brain. The effects of tDCS on whole-body exercise performance has been of interest in recent literature. The purpose of the current investigation was to investigate if tDCS, administered via Halo Sport, influences time trial performance in trained cyclists, and if changes in exercise performance are associated with prefrontal cortex (PFC) activation and/or muscle oxygenation (SmO2). Methods: Twelve recreationally trained cyclists volunteered to participate in two 10-kilometer time trials following 20 minutes of tDCS or a sham condition. Results: T-tests showed there was no significant difference in performance (time to completion) or physiological measures (BLa-, HR, SmO2, PFC oxygenation) between the Halo and sham conditions. Conclusions: These results indicate that the application of tDCS via Halo Sport does not induce changes in exercise performance or related physiological parameters during a 10-kilometer cycling time trial.

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

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

Objective: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. Methods: Subjects (3x10³ ≤ peripheral blood leukocyte levels < 8x10³ cells/μl) who met the inclusion criteria were recruited for this study. Enrolled subjects (n=120) were randomly assigned to either the PTE group (n=60) who were given 2.5 g/day of PTE (as Porphyra tenera extract) in capsule form or the placebo group (n=60) who were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed by measuring natural killer cell (NK-cell) activity, cytokines, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. Results: Compared to baseline, NK cell activity (%) increased for all effector cell to target cell ratios in the PTE group after 8 weeks, but there were no changes in the placebo group (p<0.1). Subgroup analysis of 101 subjects without an URI revealed that NK-cell activity in the PTE group tended to be increased for all E:T ratios (E:T=12.5:1 p=0.068; E:T=25:1 p=0.036; E:T=50:1 p=0.081) compared to the placebo group. There was a significant difference between these two groups for the E:T=25:1 ratio, which increased from 20.3±12.0% at baseline to 23.2±12.4% after 8 weeks in the PTE group (p=0.036). There was no significant difference in levels of cytokines between these two groups. Conclusions: PTE supplementation appears to enhance immune function by improving NK-cell activity without adverse effects in healthy adults.

In a recent paper [1], I argued against backward in time effects used by several authors to explain delayed choice experiments. I gave an explanation showing that there is no physical influence propagating from the present to the past and modifying the state of the system at a time previous to the measurement. However, though the solution is straightforward in the case of delayed choice experiments involving only one particle, it is subtler in the case of experiments involving two entangled particles because they give rise to EPR-like situations. Considering that a measurement is not an actual change of the physical state of a system and is relative to the observer allows to understand that there is neither backward in time effects nor instantaneous collapse of the second system when the first one is measured, as is often postulated. This allows also to get rid of any non-locality [2]. In this paper, I want to go further into the consequences of this way of considering the measurement, that I have called Convivial Solipsism, and show that even if, in the usual sense, there is no physical effect of the present or of the future on the past, we must nevertheless consider that the observer’s past is sometimes not entirely determined and that it becomes determined only when certain measurements are done latter. This apparent contradiction disappears if one understand that each observer builds, through her own measurements, her own world (that I call the phenomenal world in Convivial Solipsism) which is different from what we are used to consider as the common world shared by everybody.

With growing city tourism, there is an increasing need for urban travel demand models to consider traffic generated by visitors. Existing research has concentrated on socio-demographic and journey-related factors to determine what influences the mode choice of tourists. In contrast, revealed preference data, like travel time, is almost never considered. In this article, we present the results of discrete choice modeling of city tourists’ mode choice based on revealed preference data from a survey we conducted in Kassel, Germany. We used multinomial logit models and determined the model parameters using maximum likelihood estimations. Surprisingly, travel time played a smaller role in mode choice than understood from previously established knowledge about everyday mobility. In the final model, travel time was only significant for the alternative walking. Also, most other sociodemographic and journey-related variables showed no significant influence. The final model reproduced the mode choice, but the goodness of fit was lower than expected from other research. We conclude that modeling the travel behavior of tourists is more complex than everyday mobility. An alternative approach that we suggest would be to model trip chains rather than single trips.

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

Egg-laying is one of the key aspects of female reproductive behavior in insects. Egg-laying has been studied since the dawn of Drosophila melanogaster as a model organism. The female’s internal state, hormones, and external factors, such as nutrition, light, and social environment, affect egg-laying output. However, only recently, neurobiological features of egg-laying behavior have been studied in detail. Fruitless and doublesex, two key players in the sex determination pathway, have become focal points in identifying neurons of reproductive significance in both central and peripheral nervous systems. The reproductive tract and external terminalia house sensory neurons that carry the sensory information of egg maturation, mating and egg-laying. These se include the presence of male accessory gland products and mechanical stimuli. The abdominal neuromere houses neurons that receive information from the reproductive tract, including sex peptide abdominal ganglion neurons (SAGs), and send their information to the brain. In the brain, neuronal groups like aDNs and pC1clusters modulate egg-laying decision-making, and other neurons like oviINs and oviDNs are necessary for egg-laying itself. Lastly, motor neurons involved in egg-laying, which are mostly octopaminergic, reside in the abdominal neuromere and orchestrate the muscle movements required for laying the egg. Egg-laying neuronal control is important in various evolutionary processes like cryptic female choice, and using different Drosophila species can provide intriguing avenues for the future of the field.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

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

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

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

Background There is anecdotal evidence that ivermectin may decrease the frequency of seizures in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy with ≥2 seizures/month were randomly allocated to receive over a one year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs (AED). Study outcomes included seizure freedom during the last four months (primary endpoint), decrease in microfilarial density, and occurrence of adverse events. A multiple logistic regression model was used to evaluate the primary outcome. Results Of the 197 OIPWE enrolled, 100 were randomized to receive ivermectin thrice, 52 twice, and 45 once. In an intent-to-treat combined analysis of data from group 1 and 2, the probability to become seizure-free for OIPWE treated with ivermectin twice per year was significantly higher than in those treated once (OR: 5.087, 95% CI: 1.378-19.749; p=0.018) and individuals who received ivermectin twice had a 4.471 (95% CI: 0.944-6.769, p=0.075) times higher odds of seizure freedom than those received ivermectin once per year. Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p=0.027). Conclusions Increasing the number of ivermectin treatments per year was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures. Registration: www.clinicaltrials.gov; NCT03852303

Guessing effects frequently occur in testing data in educational or psychological applications. Different item response models have been proposed to handle guessing effects in dichotomous test items. However, it has been pointed out in the literature that the oftenemployed three-parameter logistic model poses implausible assumptions regarding the guessing process. The four-parameter guessing model has been proposed as an alternative to circumvent these conceptual issues. In this article, the four-parameter guessing model is compared with alternative item response models for handling guessing effects through a simulation study and an empirical example. It turned out that model selection for item response models should be rather based on the AIC than the BIC. However, the RMSD item fit statistic used with typical cutoff values was found to be ineffective in detecting misspecified item response models. Furthermore, sufficiently large sample sizes are required for sufficiently precise item parameter estimation. Moreover, it is argued that the criterion of statistical model fit should not be the sole criterion of model choice. The item response model used in operational practice should be valid with respect to the meaning of the ability variable and the underlying model assumptions. In this sense, the four-parameter guessing model could be the model of choice in educational large-scale assessment studies.

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

Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system and dysregulation of its cellular functions are associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radio-sensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Further, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.

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

This paper presents the behavior of decision makers, the possible choices and the strategies 1 resulting from the uncertainties related to the integration of renewable energies. Its uncertainties 2 are the risks associated with the volatility of renewable sources, the dynamics of energy production 3 as well as the planning and operation of the electricity grid. The goal is to model the risk-averse 4 decision-maker’s behavior and the choice of integrating renewable energies into the electrical system. 5 Following a bibliographic approach, we expose a methodology to model the decision-maker’s 6 behavior(risk aversion and predilection for risk) to risk taking. The risk-averse decision maker may 7 adopt nonlinear utility functions. Risk aversion is a behavior that reflects the desire to avoid risk 8 decisions and thus reduces the risk of adverse consequences. A decision support tool is provided to 9 the decision-maker to choose a best-fit strategy based on his preferences. The rational and risk-averse 10 decision-maker would seek to maximize a concave utility function instead of seeking to minimize its 11 cost. Taste or aversion to risk can be modeled by a thematic function of utility.

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nuclei are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved. We also call for a revised manner in which to think about choice during random X-inactivation.

As urban populations and transport demand expand, Pakistani metropolitan centers face traffic congestion and environmental challenges. This research aims to assess carpooling (CP) to alleviate traffic congestion, fuel demand, and pollution. This study was conducted in Islamabad, a fast-growing city with a high percentage of personal cars in Pakistan, to assess the travelers’ perceptions, and public acceptance of CP and determine the effects on traffic congestion, fuel consumption, and CO2 emissions. The investigation of travelers' perceptions towards CP was conducted through a stated preference questionnaire survey. A total of 700 responses from one million population of Islamabad were collected as per Sloven's Formula. SPSS and Smart PLS software were used for data analysis. Various factors influencing peoples’ travel perceptions, mode choice, and tendency to carpool, were categorized to evaluate the relationship between travelers’ perception and the tendency to carpool in the presence of mode choice as a mediating variable. Confirmatory factor analysis was conducted in SMART PLS to refine the number of scale items for each variable. One-way ANOVA, step-wise and mediated multiple regression analysis was conducted in SPSS to check the direct and mediating relationship between different variables. Moreover, the probability of reducing traffic congestion and assessing fuel reduction resulting from CP was also analyzed. The findings imply that travelers’ mode choice acts as a mediator between the relationship between travelers’ perception and tendency to carpool. Furthermore, results predicted that CP might reduce 0.25 million cars on the road, about 33.6% of the total private vehicles. Thereby, saving up to 546,810 barrels per year, about 3.42% of Pakistan's total petrol consumption. The findings of this study could be helpful for transport planners, environmentalists, and policymakers to implement carpool systems. Thus, reducing traffic congestion and harmful CO2 emissions and maintaining a sustainable environment.

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

Mate choice that is based on behavioural traits is a common feature in the animal kingdom. Using the Trinidadian guppy, a species with mutual mate choice, we investigated whether males use female swimming activity – a behavioural trait known to differ consistently among individuals in many species – as a trait relevant for their mate choice. In a first experiment, we assessed male and female activity in an open field test alone (two repeated measures) and afterwards in heterosexual pairs (two repeated measures). In these pairs, we simultaneously assessed males’ mating efforts by counting number of sexual behaviours (courtship displays and copulation). Male and female guppies showed consistent individual differences in their swimming activity when tested both alone and in a pair, and these differences were maintained across both test situations. When controlling for male swimming behaviour and both male and female body size, males performed more courtship displays towards females with higher swimming activity. In a second experiment, we tested for a directional male preference for swimming activity by presenting males video animations of low and high active females in a dichotomous choice test. In congruence with experiment 1, we found males to spend significantly more time in association with the high active female stimulus. Both experiments thus point towards a directional male preference for higher activity levels in females. We discuss the adaptive significance of this preference as activity patterns might indicate individual female quality, health or reproductive state while, mechanistically, females that are more active might be more detectable to males as well.

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

Background: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of the stoves, with simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. Methods: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda either to a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). Results: 1585 women received the intervention, at a median (interquartile range) of 8.0 (5.0–15.0) days post-randomization and gestational age of 17.9 (15.4–20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of intervention households. 31.4% removed their traditional stoves upon receipt of the intervention, and among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). Conclusions: Fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high.

The phenomenon of quantum erasure exposed a remarkable ambiguity in the interpretation of quantum entanglement. On the one hand, the data is compatible with the possibility of arrow-of-time violations. On the other hand, it is also possible that temporal non-locality is an artifact of post-selection. Twenty years later, this problem can be solved with a quantum monogamy experiment, in which four entangled quanta are measured at the same time. If Bell violations can be recovered from a “monogamous” quantum system, then the arrow of time is obeyed at the quantum level.

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

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

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

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

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

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