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Introduction: We developed low-cost, portable paper-based diagnostic devices for detection of human immunoglobulin M (IgM) and immunoglobulin G (IgG) in serum without any sample preparation. These devices can be used to help identify presence of diseases, used to provide rapid results (<5 minutes), readily used by untrained personnel, employed in austere environments, configured to obtain multiplexed assays, and easily disposed of.Materials and Methods: We successfully accomplished colorimetric detection of human IgG and human IgM using a sandwich-style assay within the microfluidic paper device via vertical flow immunoassay configuration. The reaction zone in the wax printed paper layer is a small circular pattern. Gold nanoparticles conjugated with anti-human IgG and IgM antibodies have been used for colorimetric detection of IgG or IgM by naked eye. Colorimetric signal can be precisely quantified through implementation of image analysis software which can be developed as an app for a smartphone. The size of the device is 2 cm × 2 cm × 1 mm.Results: Colorimetric detection of human IgG was accomplished at 100 fg/mL concentration using a gold nanoparticle-conjugated anti-human IgG antibody. The developed platform has a dynamic range of IgM and IgG concentrations between 0.1 pg/mL and 100 μg/mL. These devices provided a color readout in <5 minutes using 20 µL of serum. We also demonstrated that the devices show a significant degree of ruggedness and temperature stability as they were able to provide satisfactory results (detection of 0.1 pg/mL IgG) after 14 days of long stability and shelf-life experiment at an elevated temperature of at least 50 ˚C-the shelf life can be as long as 180 days under ambient conditions for detection of 100 µg/mL IgG.Conclusions: Because of the inherent simplicity of the device operation and their ease of use, there is no variation between samples and users of the device. This low-cost approach enables multiplexing with >1 measurement performed in parallel at the same time. We anticipate that because of the sensitivity, specificity, ease of use, and overall reliability, this approach will become a standard for diagnosis of diseases and health conditions. [ABSTRACT FROM AUTHOR]

Background The extensive and continuous reuse of sensitive health data could enhance the role of population health research on public decisions. This paper describes the design principles and the different building blocks that have supported the implementation and deployment of Population Health Information Research Infrastructure (PHIRI), the strengths and challenges of the approach and some future developments. Methods The design and implementation of PHIRI have been developed upon: (i) the data visiting principle—data does not move but code moves; (ii) the orchestration of the research question throughout a workflow that ensured legal, organizational, semantic and technological interoperability and (iii) a 'master–worker' federated computational architecture that supported the development of four uses cases. Results Nine participants nodes and 28 Euro-Peristat members completed the deployment of the infrastructure according to the expected outputs. As a consequence, each use case produced and published their own common data model, the analytical pipeline and the corresponding research outputs. All the digital objects were developed and published according to Open Science and FAIR principles. Conclusion PHIRI has successfully supported the development of four use cases in a federated manner, overcoming limitations for the reuse of sensitive health data and providing a methodology to achieve interoperability in multiple research nodes. [ABSTRACT FROM AUTHOR]

This paper aims to guide the stakeholder engagement process related to plastic pollution research in marine environments. We draw on advice identified during an online workshop (Ocean Plastic Workshop 2022) organized by Early Career Ocean Professionals (ECOPs) from 11 countries, held in April 2022. International experts and workshop participants discussed their experiences in the collaborative development and implementation of ocean plastic pollution projects held worldwide, guided by three main questions: (i) What is the role of scientists in a multi-stakeholder project? (ii) How should scientists communicate with other stakeholders? (iii) Which stakeholders are missing in collaborative projects, and why are they missing? This multidisciplinary, co-learning approach highlights the value of stakeholder engagement for ocean plastic projects with an end goal to identify and implement ocean plastic solutions via innovative technologies, informing policy, community engagement, or a combination of all three approaches. The target outcomes of the workshop described in this paper include the identification of transdisciplinary (academic-stakeholder) engagement frameworks and specific suggestions that can serve as guidelines for the development of future plastic pollution projects. [ABSTRACT FROM AUTHOR]

Princeton—Stanford Working Papers in Classics (PSWPC) is a web-based series of work-in-progress scripts by members of two leading departments of classics. It introduces the humanities to a new form of scholarly communication and represents a major advance in the free availability of classical-studies scholarship in cyberspace. This article both reviews the initial performance of this open-access experiment and the benefits and challenges of working papers more generally for classical studies. After 2 years of operation PSWPC has proven to be a clear success. This series has built up a large international readership and a sizeable body of pre-prints and performs important scholarly and community- outreach functions. As this performance is largely due to its congruency with the working arrangements of ancient historians and classicists and the global demand for open-access scholarship, the series confirms the viability of this means of scholarly communication, and the likelihood of its expansion in our discipline. But modifications are required to increase the benefits this series brings and the amount of scholarship it makes freely available online. Finally, departments wishing to replicate its success will have to consider other important developments, such as the increasing availability of post-prints, the linking of research funding to open access, and the emergence of new cyber-infrastructure. [ABSTRACT FROM AUTHOR]

Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health. The importance of ID research in understanding diseases, leading to treatments and vaccines, is emphasized, along with the need to address persistent and new infections, antimicrobial resistance, and threats like HIV and influenza. The paper analyzes the physician-scientist workforce's struggles, including funding, training, and research-practice integration gaps. We suggest increased funding, better training, and mentorship, more collaborative and interdisciplinary research, and improved recognition systems. The article stresses the urgency of supporting physician-scientists in ID, advocating for proactive prevention and preparedness, and calls for immediate action to enhance ID research and care. [ABSTRACT FROM AUTHOR]

Background Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. Methods In the VOICE community—a European healthcare centre cluster intending to address VBHC from theory to practice—information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. Results Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. Conclusions To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions. [ABSTRACT FROM AUTHOR]

In recent years, research on the psychological aspects and assessment of video games has become more and more important due to their impact in entertainment and education. The development of psychometric instruments to measure different factors of a player’s engagement and skills in playing video games and to measure different factors of the game’s playability and attractiveness is essential to this research. This article reviews two papers on measuring the player’s subjective experiences playing the game by IJsselsteijn et al. (2007, Characterising and Measuring User Experiences in Digital Games. ACE Conference ’07, June 13–15, Salzburg, Austria) and the player’s level of engagement in playing games by Brockmyer et al. (2009, The Development of the Game Engagement Questionnaire: A Measure of Engagement in Video Game-playing. J. Exp. Soc. Psychol., 45, 624–634). While approaching the topic with very different purposes and methodologies, both papers contribute important ideas and useful scales that should be used by researchers in the field. [ABSTRACT FROM PUBLISHER]

Highly cited articles are very different from 'ordinary' cited articles. Typically, they are authored by a large number of scientists, often involving international collaboration. The majority of the papers represent regular journal articles (81%), although review articles (12%) are over-represented compared to the national average. The citation curves of highly cited papers follow a typical pattern of rise and decline. However, different types of citation curves can be identified, reflecting possible differences in the cognitive function of the articles. Highly cited papers typically obtain citations from a large number of different journals and from papers representing both close and remote fields. However, this pattern is not very different from the average distribution for all papers. We discuss how the findings can be explained by introducing a conceptual distinction between quality dynamics and visibility dynamics. [ABSTRACT FROM AUTHOR]

During this centennial year of the American Society of Animal Science (ASAS), it is of interest to look back over the history of our Society and, in particular, to the many contributions made by researchers in the area of swine nutrition. A great number of basic and applied research studies involving the nutrition of weanling, growing, and finishing pigs, and gestating and lactating sows have been conducted by swine nutritionists during the past 100 yr. Most of these studies were conducted at universities by animal scientists or by the graduate students under their leadership. Others were conducted by nutritionists in the feed and pharmaceutical industries and government scientists at ARS/USDA research centers. Contributions were also made by animal scientists beyond our borders. Much of the research was published in the Journal of Animal Science during its 66 yr of existence. Before the first issue of the journal was published in 1942, some of the earlier studies were reported in the Proceedings of the Annual Meeting of the Society of Animal Production, the forerunner of ASAS. These research studies have progressively led to a better understanding of the role and utilization of dietary energy, protein, AA, carbohydrates, fats, minerals, and vitamins by pigs and have helped to quantify the nutrient requirements of pigs for various stages of growth, for sows during gestation and lactation, and to a limited extent, for boars. Determining the nutritional value of a wide array of feedstuffs, evaluating feeding strategies, and assessing the value of growth-promoting and carcass-enhancing agents have been important research contributions as well. To identify the particular studies that were among the most instrumental in contributing to our present knowledge of swine nutrition is, to say the least, a daunting assignment. To aid in this task, a survey of swine nutritionists was conducted in which they were asked to identify and rank the 10 most significant findings in swine nutrition during the past 100 yr. The results of that survey are presented in this paper. [ABSTRACT FROM AUTHOR]

Forage-animal production agriculture is implementing infrastructure changes and management strategies to adjust to increased energy-related costs of fuel, feed grains, fertilizers, and seeds. The primary objectives of this position paper are to assess future research and extension scientific needs in forage utilization, financial support for the discipline, and changing status and number of scientists. A survey questionnaire returned from 25 land-grant universities in the eastern half of the United States rated the top 4 research needs as 1) pasture systems and efficiency of production; 2) interfacing with energy concerns; 3) forage cultivar evaluations and persistence; and 4) environment impacts. Plant-animal future research needs at 11 USDA-ARS regional locations are targeted at sustainable management and improved livestock performance, ecophysiology and ecology of grasslands, environment impacts, and improved technologies for nutritive value assessments. Extension scientists from 17 southern and northeastern states listed the top 3 needs as forage persistence, soil fertility and nutrient management, and pasture systems and efficiency of production. Grant funds currently provide more than 40% of land-grant university research and extension efforts in forage utilization, and scientists estimate that this support base will increase to 55 to 60% of the funding total by 2013. Reduced allocation of state and federal funding has contributed to a reduction in the number of full-time equivalent (FTE) scientists engaged in forage utilization research and extension activities. The current 25 state FTE conducting research number about 2.8 per state. This includes 10 states with >3, 11 states with <2, and 3 states with <1 FTE. Increased interest in cellulosic energy, climate change, and environmental impact may offer new opportunities for these FTE to participate in integrated cross-discipline research Extension programming, and technology transfer methods will change to accommodate reduced funding but with increasing numbers of novice, recreation-oriented landowners. [ABSTRACT FROM AUTHOR]

A multirepeat in a string is a substring (factor) that appears a predefined number of times. A multirepeat is maximal if it cannot be extended either to the right or to the left and produce a multirepeat. In this paper, we present algorithms for two different versions of the problem of finding maximal multirepeats in a set of strings. In the case of arbitrary gaps, we propose an algorithm with O(σN2n + α) time complexity. When the gap is bounded in a small range c, we propose an algorithm with O((c2 + σ2)mN2n log(Nn) + α) time complexity. Here, N is the number of strings, n the mean length of each string, m the multiplicity of the multirepeat and α the number of reported occurrences. Our results extend previous work by considering sets of strings as well as by generalizing pairs to multirepeats. [ABSTRACT FROM AUTHOR]

From a historical perspective, it is difficult to identify a specific date that launched the field of endocrinology. One "biomarker" of the inception of endocrinology traces back to Ernest Henry Starling, who first introduced the word hormone in a talk given in 1905 at the Royal College of Physicians in London (Starling, 1905). A historical look at the field of endocrine regulation of animal growth since 1905 conveys that countless scientists worldwide worked to advance the scientific evidence base, which led to the commercial development of hormone-based products that enhanced growth and beneficially changed carcass composition of meat animals. This review will discuss some of seminal contributions that include the discovery of hormones (like ST and β-adrenergic agonists) that have been shown to play key roles in regulating growth and nutrient partitioning of livestock, the mechanisms by which these hormones act, and the development of products for application in animal agriculture. [ABSTRACT FROM AUTHOR]

Discoveries, understanding, and innovations in meat science during the last century have led to revolutionary changes in meat and poultry production, processing, marketing, and consumption. American Society of Animal Science members have made key contributions in most, if not all, categories of advancement. The first US university meat science program was begun in Minnesota in 1905. Use of mechanical refrigeration in the meatpacking industry, improved transportation and packaging, and home refrigeration provided more flexibility, variety, and consistency in meat and meat products in the early 1900s. Cooperative meat research was begun by 27 universities in 1925, with a focus on the observational characterization of carcass traits and composition, meat quality attributes, and causes of the wide variation in these variables. Scientific study of genetic, nutritional, and environmental influences on the growth, physiology, and postmortem biochemistry of muscle often used muscle-comparative investigations. Rigor mortis, cold shortening and thaw rigor, postmortem muscle metabolism, postmortem tenderization and tenderness variation, and postmortem myoglobin and lipid oxidation were studied vigorously in the 1960s and beyond, defining the biochemical bases for associated outcomes in fresh and processed products. Value-added benefits resulted from implementation of electrical stimulation, boxed beef and modified-atmosphere packaging, restructuring technologies, collagen recovery, and muscle profiling work. Isolation, purification, and definition of the primary structure and biophysical properties of the myofribillar and cytoskeletal proteins in muscle aided the understanding of contraction and postmortem changes. The role of Ca-dependent proteases in meat tenderness and muscle growth is being clarified. The chemistry of meat curing, meat emulsion formation, fermentation, and other processing methods led to new technologies, new meat products, and new benchmarks in product shelf life and quality. Meat safety assurance and our ability to manage the microbiological causes of food-borne illness and spoilage are imminently important now and in the future. [ABSTRACT FROM AUTHOR]

Over the next quarter century in North America, the following eventualities are likely for physiology and endocrinology research with agricultural animals. 1) Total funding adjusted for inflation will change little but will come less from public sources, and most of that will be in the context of human health. Much of the privately funded research will be herd specific and remain proprietary. 2) The numbers of MS, PhD, and postdoctoral students probably will decrease, but research in the context of credentialing will remain important. 3) Resources such as expanded databases in genomics and proteomics, and remarkable new tools such as small inhibitory RNA will continue to become available, likely at a faster rate than in the previous 25 yr. 4) The huge amounts of data from production agriculture will make agricultural animals ideal models for some kinds of basic research, such as studying fetal programming, resulting in synergy with more applied research. Most of these experimental animals will be in private production herds and flocks, even when work is publicly funded. 5) The trend toward more interdisciplinary research will continue, especially considering interactions among reproduction, health, nutrition, selective breeding, management factors, and societal concerns; reductionist research probing deeper into cellular and molecular mechanisms will remain important, as will whole-animal approaches. 6) Agricultural animals are a product of evolution plus selective breeding. Insights drawn from the former will aid progress in the latter. One focus of research in physiology and endocrinology will be understanding heterosis, inbreeding depression, and epigenetic effects as it becomes possible to manipulate and identify the allelic structure of individual animals. 7) Additional insightful concepts will evolve that will simplify thinking in some respects, such as the maternal to embryonic shift in transcribed RNA in early embryos; however, animal biology will turn out to be even more complex than most of us currently imagine. [ABSTRACT FROM AUTHOR]

Departments of animal sciences must be relevant to a society in which a small number of people can raise almost all the food animal products needed. The declining number of people involved in animal agriculture has decreased enrollment of students interested in food animals in many departments of animal science. However, several departments welcomed students from a diverse background and began research on animals other than food animals. In many states, the undergraduate enrollment is made up primarily of students interested only in companion animals. A benefit of this is that we have recruited new students into animal agriculture and they have gone on to excellent careers. We have a new challenge now: how to maintain and expand the efforts in teaching, research, and outreach of companion animal science. Departments wishing to expand in teaching have examples of successful courses and curricula from other departments. Some departments have expanded their teaching efforts across their own university to teach about pets to a wider audience than their own majors; other departments can follow. In research, a small number of faculty have been able to establish extramurally funded projects on pets, including horses. But it will be difficult for more than a handful of departments to have a serious research effort in dogs, cats, birds, fish, or exotic animals. Departments will have to make a concerted effort to invest in such endeavors; joint ventures with other universities and colleges of veterinary medicine (or medicine) will probably be required. Funding sources for "traditional" efforts in nutrition, reproduction, and physiology are small and inconsistent; however, with the progress of the equine, canine, and feline genome projects, there should be opportunities from federal funding sources aimed at using animal models for human health. In addition, efforts in animal behavior and welfare can be expanded, perhaps with some funding from private foundations or animal-supportive organizations. [ABSTRACT FROM AUTHOR]

Goat research in the United States has increased but at a rate less than that in production. Research on goat meat includes nutritional quality, packaging, color, sensory characteristics, and preslaughter management. Goat skins have value for leather, but quality of goat leather has not been extensively studied. Research in the production, quality, antibiotic residues, and sensory characteristics of goat milk and its products has aided development of the US dairy goat industry. Limited progress has been made in genetic improvement of milk or meat production. There is need to explore applications of genomics and proteomics and improve consistency in texture and functionality of goat cheeses. New goat meat and milk products are needed to increase demand and meet the diverse tastes of the American public. Despite research progress in control of mohair and cashmere growth, erratic prices and sale of raw materials have contributed to further declines in US production. Innovative and cooperative ventures are needed for profit sharing up to the consumer level. Internal parasites pose the greatest challenge to goat production in humid areas largely because of anthelmintic resistance. Study of alternative controls is required, including immunity enhancement via nutrition, vaccination, pasture management such as co-grazing with cattle, and genetic resistance. Similarly, the importance of health management is increasing related in part to a lack of effective vaccines for many diseases. Nutrition research should address requirements for vitamins and minerals, efficiencies of protein utilization, adjusting energy requirements for nutritional plane, acclimatization, and grazing conditions, feed intake prediction, and management practices for rapid-growth production systems. Moreover, efficient technology transfer methods are needed to disseminate current knowledge and that gained in future research. [ABSTRACT FROM AUTHOR]

One hundred years ago, there were more than 48 million sheep in the United States. In 1910, they were valued at $4/head, with 43% of income coming from the sale of sheep, lambs, and meat and 57% coming from wool. Over the years, fluctuations in this ratio have challenged the breeder and researcher alike. By 2007, sheep numbers had declined to 6.2 million, with the average sheep shearing 3.4 kg of wool (representing <10% of income), 0.2 kg more than in 1909 but 0.5 kg less than fleeces in 1955. Sheep operations have declined by more than 170,000 in the past 40 yr. A cursory examination of this information might lead one to conclude that animal science research has made little impact on sheep production in the United States. On the contrary, lamb crops in the new millennium (range = 109 to 115%) are greater than those recorded in the 1920s (85 to 89%) and dressed lamb weights increased from 18 to 32 kg from 1940 to the present. In the past century, researchers conducted thousands of investigations, with progress reported in new, existing, and crossbreed evaluations, quantitative and molecular genetics, selection, nutrition, fiber, meat, hides, milk, growth, physiology, reproduction, endocrinology, management, behavior, the environment, disease, pharmacology, toxicology, and range, pasture, and forage utilization such that a vast amount of new information was accrued. Our understanding of sheep has benefited also from research conducted on other species, and vice versa. Many factors that have contributed to the decline in the sheep industry are not influenced easily by academic research (e.g., low per capita consumption of lamb meat, predation, reluctance to adopt new technologies, cost and availability of laborers with sheep- related skills, and fewer young people pursuing careers in agriculture). The size of the US sheep industry is expected to remain stable, with possible slow growth in the foreseeable future. To remain profitable, producers will take advantage of new (or previously unused) technologies, the desire of the public for things natural, domestic niche and international fiber markets, and the ability of the sheep to control noxious weeds and thrive in suboptimal ecosystems. [ABSTRACT FROM AUTHOR]

Objectives Research among older adults reveals that the loss of core network members is a risk factor for loneliness. Still, it is not clear whether all such losses induce similar levels of loneliness, particularly as network members are distributed at varied geographic distances. Neither is it clear whether tie addition—the other ubiquitous aspect of network turnover in later life—offsets the loneliness that arises from different network loss scenarios. Methods This paper scrutinized core network losses across multiple relationship–distance scenarios. We used the fourth and sixth waves of data from the Survey of Health, Ageing, and Retirement in Europe and estimated fixed-effect models. Results The loss of a child from a core network increases feelings of loneliness across variant distances, especially when not complemented by additional connections. Losing relatives or nonkin core connections in proximity (within 1 km and 5 km radius, respectively) is also associated with increased loneliness, yet such effects are also largely mitigated by the addition of new core network members. Discussion The relationship between core network member losses and loneliness can significantly differ based on the nature of the lost connection and its geographic distance. Active rebalancing of one's core network following losses and proactive network expansion can serve as pivotal strategies to prevent loneliness for the aging population. [ABSTRACT FROM AUTHOR]

Calls for professional papers for presentation at the mid-year Clinical Meeting of the American Society of Health-System Pharmacists in Orlando, Florida. Changes in the submission process to improve the quality of the presentations; Deadline for Management Case Study, professional, student and resident poster submissions; Selection criteria that will be used by a blinded peer review panel.

A large number of observational studies have found a J-shaped relationship between alcohol intake and ischemic heart disease (IHD) risk. However, some studies suggest that the alleged cardio-protective effect may be an artifact in the way that the elevated risk for abstainers is due to self-selection on risk factors for IHD. The aim of this paper is to estimate the association between alcohol and IHD-mortality on the basis of aggregate time-series data, where the problem with selection effects is not present. In addition, we will analyze SES-specific mortality to investigate whether there is any socio-economic gradient in the relationship at issue. SES was measured by educational level. We used IHD-mortality in three educational groups as outcome. Per capita alcohol consumption was proxied by Systembolaget's alcohol sales (litres of alcohol 100% per capita 15+). Swedish quarterly data on mortality and alcohol consumption spanned the period 1991Q1–2020Q4. We applied SARIMA time-series analysis. Survey data were used to construct an indicator of heavy SES-specific episodic drinking. The estimated association between per capita consumption and IHD-mortality was positive and statistically significant in the two groups with primary and secondary education, but not in the group with postsecondary education. The association was significantly stronger the lower the educational group. Although the associations were generally stronger for males than for females, these differences were not statistically significant (P  > 0.05). Our findings suggest that the detrimental impact of per capita consumption on IHD-mortality was stronger the lower the educational group. [ABSTRACT FROM AUTHOR]

Objective A brain health equity neuropsychology research framework (NRF) is crucial to the anti-racist movement in cognitive assessments. Universalist interpretation of neuropsychological tools contributes to systemic disparities, and there is a need for a clear conceptual framework for disentangling the direct and indirect impact of social determinants of health (SDH) on brain-behavior relationships and neuropsychological performance. The aim of this paper is to present a NRF anchored in the principles of brain health and health equity that is inclusive, and can be implemented across racially and ethnically diverse communities. Methods The Re-engaging Individuals and societies for Structural Evolution (RISE) NRF aims to address this via a two-pronged approach: 1. Focusing on community engagement and recruitment and retention of individuals and societies typically not equitably represented in brain health studies, and 2. Integrating the conceptual structure of individual, community, and SDH, while considering the broader historical and current structures that differentially shape these. Results The proposed RISE NRF is dynamic and multidirectional. It identifies barriers and proposes strategies to engage communities and diversify recruitment. It identifies evidence-based guidance on non-cognitive determinants of health to include, consider or explore in brain health research. Conclusion The RISE NRF can guide the development of culturally and linguistically responsive methodologies and assist with clearly conceptualized and contextualized interpretation of neuropsychological tools to foment a transformative science that benefits the brain health of marginalized communities. [ABSTRACT FROM AUTHOR]

Aims A mediator is a variable that explains the underlying mechanism between an independent variable and a dependent variable. The indirect effect indicates the effect from the predictor to the outcome variable via the mediator. In contrast, the direct effect represents the predictor's effort on the outcome variable after controlling for the mediator. Methods A single study rarely provides enough evidence to answer research questions in a particular domain. Replications are generally recommended as the gold standard to conduct scientific research. When a sufficient number of studies have been conducted addressing similar research questions, a meta-analysis can be used to synthesize those studies' findings. Results The main objective of this paper is to introduce two frameworks to integrating studies using mediation analysis. The first framework involves calculating standardized indirect effects and direct effects and conducting a multivariate meta-analysis on those effect sizes. The second one uses meta-analytic structural equation modeling to synthesize correlation matrices and fit mediation models on the average correlation matrix. We illustrate these procedures on a real dataset using the R statistical platform. Conclusion This paper closes with some further directions for future studies. [ABSTRACT FROM AUTHOR]

Care homes enable people with advanced physical and cognitive impairment to live well with 24-h support from staff. They are a feature of care systems in most countries. They have proved pivotal to the coronavirus disease 2019 (COVID-19) response. We searched Age and Ageing for care-home articles published since 2015. From these we collated 42 into the Age and Ageing care-home collection. This collection draws together important papers that show how Age and Ageing is helping to shape and grow care-home research. The   collection outlines the technical issues that researchers face by grouping together important feasibility trials conducted in the sector. It looks at the challenges of measuring quality of life and working with routine data in care homes. It brings together observational studies considering loneliness, functional dependency, stroke outcomes, prescribing and acute deterioration. Health services research in care homes is represented by two studies that demonstrate realist evaluation as a way to make sense of service innovations. Papers are included that consider: non-pharmacological strategies for residents with dementia, end-of-life care, sexuality and intimacy and the care-home workforce. Given the importance of the COVID-19 pandemic in care homes, all of the care home COVID-19 papers published in Age and Ageing to date are included. Finally, a group of papers that present innovative approaches to research in care homes, each of which give voice to residents and/or staff, are collated and presented as a way of moving towards a more resident and care home centred research agenda. [ABSTRACT FROM AUTHOR]

The knowledge of the gestational age of the newborn is essential for management. In the absence of a dating scan, the postnatal assessment scores have drawbacks of being difficult to learn and administer in the community. The measurement of the foot length is easy, reproducible and offers an objective assessment. The objective of this study was to determine the correlation of postnatal (<48 h) foot length measurement (with calipers) with gestational age as determined by antenatal dating ultrasound, create a predictive model for the same and propose foot length measurement cutoffs for <37 and <34 weeks of gestation. Secondary objectives were to assess the correlation between foot length as measured with calipers and that measured with a ruler and a paper footprint. This was a hospital-based cross-sectional study. Among the 520 babies assessed, the correlation of foot length with gestational age was 0.89. Operational cutoffs for the categories of <37 and <34 weeks at a sensitivity of 95% were <70 and <65 mm, respectively. The Pearson's correlation between foot length as measured by caliper and ruler was 0.95 and between caliper and paper footprint was 0.87. This study correlating foot length and gestational age has the potential to help neonatal care providers make informed management decisions, particularly in resource-limited settings. [ABSTRACT FROM AUTHOR]

Study Question: Are there temporal trends of sperm concentration (SC) and total sperm count (TSC) in Chinese healthy males from 1981 to 2019?Summary Answer: Our result indicated a temporal decrease in SC and TSC among 327 373 healthy Chinese men in the recent four decades.What Is Known Already: A review of 61 papers reported a temporal decline in SC and TSC from 1938 to 1990. This trend was later confirmed by a systematic review of 185 published papers from 1981 to 2013. However, the majority of the included individuals were from western countries. In China, whether SC and TSC have declined remains controversial.Study Design, Size, Duration: This systematic review of published articles used data extracted from Pubmed, Science Direct, Embase, China-National-Knowledge-Infrastructure (CNKI) and Wanfang Data to assess changes in SC and TSC in China from 1981 to 2019.Participants/materials, Setting, Methods: A total of 111 studies including 327 373 individuals who provided semen samples from 1981 to 2019 were extracted for the present analysis. Study selection and data extraction were performed by two independent researchers. The trends in SC and TSC were analysed using liner-regression and meta-regression before and after adjusting for potential covariates. Moreover, subgroups, categorised based on geographic region, fertility status or recruitment source, were also analysed.Main Results and the Role Of Chance: SC declined significantly (slope liner-regression = -0.748 million/ml/year; P = 0.005; slope meta-regression = -0.824 million/ml/year; P < 0.001) between 1981 and 2019 in China. Trends for TSC was similar to that for SC (slope liner-regression = -2.073 million/year; P = 0.032; slope meta-regression = -2.188 million/year; P = 0.003). In subgroup meta-regression analyses, males with definite fertility had continuous declines in SC (slope northern group=-2.268, P = 0.009; slope southern group=-1.014, P = 0.009) and TSC (slope northern group=-9.675, P = 0.010; slope southern group=-3.215, P = 0.042). However, in the unselected group, where fertility status was unknown, the obvious downward trend in SC was only seen in males from Northern regions (slope = -0.836, P = 0.003). Another subgroup analysis demonstrated that obvious decreases in SC (slope = -1.432, P < 0.001) and TSC (slope=-4.315, P = 0.001) were only seen in volunteer groups but not in pre-pregnancy examination groups and other recruitment groups. The results changed minimally in multiple sensitivity analyses.Limitations, Reasons For Caution: The validity of the meta-analysis results was limited mainly by the quality of the included studies. Additionally, our study spanned many decades and the recommended criteria for some semen parameter assessments have significantly changed, which may bring about some unavoidable bias. Moreover, the data remain insufficient especially in some provinces of China.Wider Implications Of the Findings: The present study is the first study to report significant decreases in SC and TSC in 327 373 healthy Chinese men between 1981 and 2019, indicating a serious reproductive health warning. Further studies on the causes of the declines are urgently needed.Study Funding/competing Interest(s): D.Z. is supported by the National Natural Science Funding of China, Natural Science Funding of Shaanxi Province, Science Funding of Health Department, Shaanxi Province, Fundamental Research Funds for the Central University and the Project of Independent Innovative Experiment for Postgraduates in Medicine in Xi'an Jiaotong University. The authors have no conflicts of interests to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

International research and collaboration has been a part of the National Cancer Institute's (NCI) mission since its creation in 1937. Early on, efforts were limited to international exchange of information to ensure that US cancer patients could benefit from advances in other countries. As NCI's research grant portfolio grew in the 1950s, it included a modest number of grants to foreign institutions, primarily in the United Kingdom and Europe. In the 1960s, the development of geographic pathology, which aimed to study cancer etiology through variations in cancer incidence and risk factors, led to an increase in NCI-funded international research, including research in low- and middle-income countries. In this paper, we review key international research programs, focusing particularly on the first 50 years of NCI history. The first NCI-led overseas research programs, established in the 1960s in Ghana and Uganda, generated influential research but also struggled with logistical challenges and political instability. The 1971 National Cancer Act was followed by the creation of a number of bilateral agreements with foreign governments, including China, Japan, and Russia, to support cooperation in technology and medicine. Although these agreements were broad without specific scientific goals, they provided an important mechanism for sustained collaborations in specific areas. With the creation of the NCI Center for Global Health in 2011, NCI's global cancer research efforts gained sustained focus. Because the global cancer burden has evolved over time, increasingly impacting low- and middle-income countries, NCI's role in global cancer research remains more important than ever. [ABSTRACT FROM AUTHOR]

Introduction: The number and variety of alternative tobacco and nicotine products that can potentially provide reduced-risk choices for cigarette smokers who switch completely to such products instead of continued smoking have grown substantially in the past decade. Innovation and choice are likely to improve the prospects of smokers making the switch, but this provides challenges to regulators and manufacturers to ensure that changes to regulations and products promote and do not hinder contributions to tobacco harm reduction.Aims and Methods: This paper looks at where bridging data sets for tobacco heating products, closed system vaping products, and oral nicotine products might enable innovation while protecting the interests of consumers.Results: We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones.Conclusions: Bridging across specific product ranges can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality.Implications: Bridging partial data sets is an established practice within other industries, that aims to improve efficiency with regulatory approvals, accepts natural product variation, and supports product innovation. We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones. This in turn can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality. [ABSTRACT FROM AUTHOR]

Introduction: In India, 38.7% of adults are exposed to SHS at home and 30.2% at work. This paper estimates the direct economic costs of diseases attributable to secondhand smoking (SHS) in India for persons aged 15 years and above.Aims and Methods: Nationally representative data on healthcare expenditures, healthcare utilization, and SHS prevalence were used to estimate economic costs attributable to SHS. A prevalence-based attributable risk approach was used for estimating the attributable direct costs. To estimate the SHS-attributable fraction, the excess utilization of healthcare among SHS exposed non-smokers compared to unexposed non-smokers was estimated using a method of propensity score matching (PSM).Results: The annual direct economic costs attributable to SHS from all diseases in India in the year 2017 for persons aged more than 15 years amounted to INR 566.7 billion (USD 8.7 billion). This amounted to INR 705 per adult non-smoker. The SHS attributable costs were higher among the youngest age group 20 to 24, and women bear 71% of the direct medical costs attributable to SHS.Conclusions: The annual direct economic costs of SHS amount to approximately 0.33% of India's Gross Domestic Product (GDP), or 8.1% of total healthcare expenditures in India. It is also much larger than the total excise tax revenue from cigarettes and bidis. As bidi smoking is the most popular form of smoking in India and bidis are mostly consumed by the poor, a disproportionate burden of SHS is likely borne by poor households in India.Implications: In India, 38.7% of adults are exposed to SHS at home and 30.2% at work. However, there is no estimate of the economic burden of any kind from SHS exposure in India. This study used a prevalence-based attributable risk approach combined with a PSM technique to estimate excess healthcare utilization for SHS exposed non-smokers and the annual direct economic costs of SHS in India. Annual direct SHS-attributable costs in India is INR 566.7 billion (USD 8.7 billion) SHS costs constituted 0.33% of GDP and 8.1% of healthcare expenditures in India. [ABSTRACT FROM AUTHOR]

This paper assesses the challenges and the benefits of 2 methodological approaches for improving the study of transnational mobilities of older adults: mixed methods and inclusiveness. The first approach refers to a mixed-methods research design based on surveys and qualitative interviews. We share our experience of conducting a "fully mixed-concurrent-equal-status-design" research project, for which we collected data through quantitative surveys on transnational practices of people aged 55+. Furthermore, we conducted semistructured interviews with adults aged 64+ living or who have lived in Switzerland and spend part of the year in Spain. The second approach relates to the use of an inclusive sample diversified in terms of nationality and migration backgrounds. The inclusive design affects the formulation of questions asked to all participants (and the response options provided in the survey), as well as decisions related to language choices and translations. These elements have to be considered to ensure that older adults from different backgrounds feel included. In a research project on transnational mobility of older adults, conducting an inclusive plus mixed-methods research project pushes researchers to find strategies to balance research objectives with available resources. Maximizing the research team's methodological background appears to be a suitable approach to address different population groups while working within a budget. [ABSTRACT FROM AUTHOR]

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington's disease as a specific example, and suggest potential strategies to address these challenges. Huntington's disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington's disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington's Disease and the European Huntington's Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington's disease. [ABSTRACT FROM AUTHOR]

Introduction: The current study was designed to test the potential role of recombinant human MG53 (rhMG53) protein on protecting against alkaline-induced corneal injury in mice.Materials and Methods: A round filter paper with 2-mm diameter was soaked in 1 mol/L of NaOH solution. The mouse alkaline injury was generated by placing the filter paper directly on the cornea for 30 seconds and washed with 30-mL saline; 10 µL of rhMG53 solution (20 µg/mL) or saline control was topically administrated on the mouse corneas (twice per day for 10 days). Re-epithelialization was measured by fluorescein staining and imaged by a slit lamp equipped with a digital camera. Clinical neovascularization and opacity scores were measured every day after injury. Ten days after injury, mice were sacrificed and corneas were dissected out for flat mount staining of CD31 for neovascularization.Results: MG53 was present in both dog aqueous humor and human tears. mg53-/- corneas were more susceptible to alkaline-induced corneal injury. Topical treatment of rhMG53 improved re-epithelialization, suppressed neovascularization, and fibrosis induced by alkaline injury.Conclusions: rhMG53 may be an effective means to treat corneal wounding. [ABSTRACT FROM AUTHOR]

Introduction: The U.S. Army medics are often the first responders in the care of sick and injured soldiers on the battlefield, sick call in a Role 2 aid station and garrison clinics. Sick call medics are required to utilize the Algorithm Directed Troop Medical Care (ADTMC) to care for and then render a disposition for these soldiers. The current ADTMC manual is a thick, heavy paper manual. A desktop and smartphone application has been developed that contains the entire ADTMC manual algorithm-based content. Our goal is to enhance the medics' clinical learning and critical thinking skills while improving their evaluation, disposition, and documentation during patient encounters.Materials and Methods: The application was field-tested with the 173rd IBCT (A) while attending a field exercise at Grafenwoehr, Germany. At the unit's Role 2 tent setup, the use of the paper manual to the utilization of the same material via the ADTMC application was compared by observing the medics' workflows directly while they were caring for ill and injured soldiers.Results: Medics, while examining patients, would demonstrate 50% faster exam time using the application compared to medics using only the manual. Moreover, a 50% decrease in document processing time as a result of digitization of the paper documentation process was confirmed. The application ("app") enabled the medics to continue their screening assessments and patient disposition duties on a desktop computer or a smartphone without the need to refer to the paper manual.Conclusion: Medics, by adopting this tool, will become quicker, more efficient, and develop critical thinking skills. In other words, the ability to objectively evaluate patients in order to form a proper disposition of sick and injured soldiers during training, in the field, as well as in garrison. When utilized properly, the ADTMC application ensures that soldiers reporting to sick call are expeditiously routed to the appropriate level of care, and is a vehicle for further training for medics in the care of soldiers. [ABSTRACT FROM AUTHOR]

Background: E-values are a recently introduced approach to evaluate confounding in observational studies. We aimed to empirically assess the current use of E-values in published literature.Methods: We conducted a systematic literature search for all publications, published up till the end of 2018, which cited at least one of two inceptive E-value papers and presented E-values for original data. For these case publications we identified control publications, matched by journal and issue, where the authors had not calculated E-values.Results: In total, 87 papers presented 516 E-values. Of the 87 papers, 14 concluded that residual confounding likely threatens at least some of the main conclusions. Seven of these 14 named potential uncontrolled confounders. 19 of 87 papers related E-value magnitudes to expected strengths of field-specific confounders. The median E-value was 1.88, 1.82, and 2.02 for the 43, 348, and 125 E-values where confounding was felt likely to affect the results, unlikely to affect the results, or not commented upon, respectively. The 69 case-control publication pairs dealt with effect sizes of similar magnitude. Of 69 control publications, 52 did not comment on unmeasured confounding and 44/69 case publications concluded that confounding was unlikely to affect study conclusions.Conclusions: Few papers using E-values conclude that confounding threatens their results, and their E-values overlap in magnitude with those of papers acknowledging susceptibility to confounding. Facile automation in calculating E-values may compound the already poor handling of confounding. E-values should not be a substitute for careful consideration of potential sources of unmeasured confounding. If used, they should be interpreted in the context of expected confounding in specific fields. [ABSTRACT FROM AUTHOR]

Good data curation is integral to cohort studies, but it is not always done to a level necessary to ensure the longevity of the data a study holds. In this opinion paper, we introduce the concept of data curation debt-the data curation equivalent to the software engineering principle of technical debt. Using the context of UK cohort studies, we define data curation debt-describing examples and their potential impact. We highlight that accruing this debt can make it more difficult to use the data in the future. Additionally, the long-running nature of cohort studies means that interest is accrued on this debt and compounded over time-increasing the impact a debt could have on a study and its stakeholders. Primary causes of data curation debt are discussed across three categories: longevity of hardware, software and data formats; funding; and skills shortages. Based on cross-domain best practice, strategies to reduce the debt and preventive measures are proposed-with importance given to the recognition and transparent reporting of data curation debt. Describing the debt in this way, we encapsulate a multi-faceted issue in simple terms understandable by all cohort study stakeholders. Data curation debt is not only confined to the UK, but is an issue the international community must be aware of and address. This paper aims to stimulate a discussion between cohort studies and their stakeholders on how to address the issue of data curation debt. If data curation debt is left unchecked it could become impossible to use highly valued cohort study data, and ultimately represents an existential risk to studies themselves. [ABSTRACT FROM AUTHOR]

Objectives: To assess the quality of evidence on the effectiveness of local US laws restricting the sale of flavored tobacco products.Methods: We conducted a systematic search and qualitative scoping review of English-language papers published through May 2020 that evaluated flavored tobacco sales policies implemented by US jurisdictions during 2010-2019. We constructed a conceptual model for flavored and menthol tobacco sales restriction outcomes, assigned GRADE quality of evidence ratings to policy outcomes evaluated through the included studies, and summarized factors that might explain weak or inconsistent findings.Results: We found moderate to high quality of evidence associating policy implementation with reduced availability, marketing, and sales of policy-restricted products, and decreased youth and adult tobacco use of these products; however, policy exclusions and exemptions, implementation challenges, tobacco industry actions (e.g., marketing of concept-named flavored products; exploiting policy exemptions for certain store types), and consumer responses (e.g., cross-border or illicit purchasing) might undermine or mitigate intended policy effects.Conclusions: Flavored and menthol tobacco product sales restrictions implemented and evaluated in US jurisdictions appear to have achieved some of their intended outcomes; however, deficiencies in study designs, methods, and metrics could contribute to equivocal findings on quality of evidence associating policy implementation and outcomes. Gaps in the evidence are beginning to be filled with research using more rigorous study designs, improved measurement and analytic methods, and longer-term follow-up.Implications: In the absence of comprehensive federal action, US jurisdictions have the obligation to restrict flavored and menthol product sales to protect vulnerable populations from tobacco-related harms. The considerable expenditure of financial resources, political will, and time dedicated to policy adoption and implementation argue for evaluation studies designed to maximize the quality of evidence. This review offers generalizable insights into evaluation findings that can inform efforts to enhance tobacco control policy implementation and impact in the US and globally. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper.Methods: An enzyme-linked immunosorbent assay (ELISA) targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection.Results: In the ELISA, the anti-EBOV IVIG was shown to have a 7-fold increase in immunoglobulin G (IgG) titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately 5- to 6-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or 2 days after infection.Conclusions: These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and postexposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses. [ABSTRACT FROM AUTHOR]

Introduction: Diversification away from tobacco production has been identified as a priority for Malawi, historically one of the world's most tobacco-reliant countries.Methods: This paper refers to a nationally representative data set to characterize broad trends in production since 2000 to understand whether Malawi is shifting away from tobacco and how production has changed over time.Results: From 2004 to 2019, the share of Malawian crop farmers producing tobacco fell from 16% to 5%, and tobacco's share of the total value of crop production also declined sharply. Tobacco farms are generally growing larger (in size and scale of production) over time. However, land productivity remains low, with net returns of 93 000 MWK (128 USD) per hectare at the median. Farm-gate prices for tobacco have declined relative to the prices of maize or fertilizer, rendering tobacco a less lucrative avenue to generate the cash income needed to purchase these key items. In addition, the share of the export price received by farmers has also declined over time, with the median farm-gate price representing 32% of the export price in 2004 and 18% in 2019.Conclusions: In some respects, a transition away from tobacco has already occurred. Additional research is needed to understand why the farm-gate share of tobacco export prices has declined over this period and how the livelihoods of smallholder farm-households that exited tobacco production have been affected.Implications: To the extent that tobacco prices appear to be declining, there is a need to rigorously assess whether farmers have suitable crop alternatives (with established markets) and other livelihood options. Likely, investments are yet needed to foster strong alternatives to tobacco; such investments include research and development in on-farm technologies to raise the productivity of non-tobacco crops, as well as improvements in non-tobacco value chains to reduce transportation costs and promote private investment. [ABSTRACT FROM AUTHOR]

Background: Changes in tobacco products, use patterns, and assessment technology in the last 15 years led the Society for Research on Nicotine and Tobacco (SRNT) Treatment Research Network to call for an update to the 2003 SRNT recommendations for assessing abstinence in clinical trials of smoking cessation interventions.Methods: The SRNT Treatment Research Network convened a group of investigators with decades of experience in conducting tobacco treatment clinical trials. To arrive at the updated recommendations, the authors reviewed the recommendations of the prior SRNT Workgroup as well as current literature. Ten additional experts in the field provided feedback on this paper and these recommendations.Results: With respect to defining abstinence, the authors recommend: (1) continuing to use the definition of no use of combustible tobacco products (regardless of use of noncombustible tobacco products [e.g., snus] and alternative products [e.g., e-cigarettes]) and collecting additional data to permit alternate abstinence definitions; (2) no use of combustible or smokeless tobacco products; and (3) no use of combustible or smokeless tobacco products or alternative products, as appropriate for the research question being addressed. The authors also recommend reporting point prevalence and prolonged abstinence at multiple timepoints (end of treatment, ≥3 months after the end of treatment, and ≥6 months postquit or posttreatment initiation).Conclusions: Defining abstinence requires specification of which products a user must abstain from using, the type of abstinence (i.e., point prevalence or continuous), and the duration of abstinence. These recommendations are intended to serve as guidelines for investigators as they collect the necessary data to accurately describe participants' abstinence during smoking cessation clinical trials.Implications: This paper provides updated recommendations for defining abstinence in the context of smoking cessation treatment clinical trials. [ABSTRACT FROM AUTHOR]

Background: The endocannabinoid system (ECS) consists of the cannabinoid receptors CB1 and CB2, the main endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and their metabolic enzymes N-acylphosphatidylethanolamine-specific phospholipase D, fatty acid amide hydrolase, diacylglycerol lipase and monoacylglycerol lipase. This system is involved in the modulation of essential physiological processes. Its role in the reproductive system has become significantly important in recent years, given its major role in events such as gametogenesis, decidualisation, implantation and placentation.Objective and Rationale: In this paper, we review the literature and summarize the role of the ECS elements in reproduction and their potential as early markers for diagnosis of reproductive disorders or as pharmacological targets for treatment.Search Methods: Original research and review papers published from 1964 to June 2019 were selected in terms of relevance, reliability and quality by searching PubMed, MEDLINE and Web of Science, using the following search terms: endocannabinoid system and endometriosis; endocannabinoid system and ectopic pregnancy; endocannabinoid system and miscarriage; endocannabinoid system and pre-eclampsia; endocannabinoid system and endometrial cancer; endocannabinoid system and reproduction; endocannabinoid, endometrium; placenta; N-acylethanolamines; anandamide; 2-arachidonoylglycerol; and cannabinoids.Outcomes: This review demonstrates relevant information concerning ECS alterations in endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. We highlight the importance of the endocannabinoids in endometrial and placental physiology and pathophysiology, from studies in vitro and in vivo and in clinical observations. The most studied of the endogenous cannabinoids is AEA. The levels of AEA were increased in plasma of patients with endometriosis and miscarriage, as well as in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial cancer. Changes in the pattern of expression of the cannabinoid receptor CB1 were also observed in endometrial biopsies of endometriosis, fallopian tube and decidua of patients with ectopic pregnancy and pre-eclamptic placenta. Moreover, alterations in CB2 expression have been reported in association with endometrial cancer. In general, studies on the cannabinoid signalling through CB2 and on the biological activities of the other major endocannabinoid, namely 2-AG, as well as its metabolic enzymes are scarce and avidly required.Wider Implications: The pathophysiological mechanisms involved in the described endometrial and placental pathologies are still unclear and lack the means for an early diagnosis. Based on current evidence, though alterations in ECS are demonstrated at tissue level, it is difficult to associate plasmatic changes in AEA with specific endometrial and placental diseases. Thus, pairing alterations in AEA levels with 2-AG and/or other endocannabinoid-like molecules may provide more accurate and early diagnoses. In addition, patients may benefit from new therapies that target the ECS and endocannabinoid signalling. [ABSTRACT FROM AUTHOR]

In a recent paper Samir Okasha has suggested an application of Arrow's impossibility theorem to theory choice. When epistemic virtues are interpreted as 'voters' in charge of ranking competing theories, and there are more than two theories at stake, the final ordering is bound to coincide with the one proposed by one of the voters (the dictator), provided a number of seemingly reasonable conditions are in place. In a similar spirit, Jacob Stegenga has shown that Arrow's theorem applies to the amalgamation of evidence; the 'voters' here are the different sources of evidence. As with Okasha's proposal, it is not clear how to avoid Arrow's pessimistic conclusion. In this paper we develop a novel argument that purports to show that, in typical examples, Arrow's result does not obtain when dealing with evidence amalgamation. The reason is that we cannot escape the well-known Duhem problem: the evidence actually confirms (or disconfirms) complex conjunctions that include various auxiliary hypotheses. We argue that confirmational holism induces us to restrict the domain of a reasonable amalgamation function, thus violating one of Arrow's conditions. The upshot is that we are now able to see the Duhem problem under a different, positive light – namely, as a phenomenon that makes the aggregation of the evidence possible in the first place, when there are at least three options on the table. [ABSTRACT FROM AUTHOR]

Background: Human male infertility has a notable genetic component, including well-established diagnoses such as Klinefelter syndrome, Y-chromosome microdeletions and monogenic causes. Approximately 4% of all infertile men are now diagnosed with a genetic cause, but a majority (60-70%) remain without a clear diagnosis and are classified as unexplained. This is likely in large part due to a delay in the field adopting next-generation sequencing (NGS) technologies, and the absence of clear statements from field leaders as to what constitutes a validated cause of human male infertility (the current paper aims to address this). Fortunately, there has been a significant increase in the number of male infertility NGS studies. These have revealed a considerable number of novel gene-disease relationships (GDRs), which each require stringent assessment to validate the strength of genotype-phenotype associations. To definitively assess which of these GDRs are clinically relevant, the International Male Infertility Genomics Consortium (IMIGC) has identified the need for a systematic review and a comprehensive overview of known male infertility genes and an assessment of the evidence for reported GDRs.Objective and Rationale: In 2019, the first standardised clinical validity assessment of monogenic causes of male infertility was published. Here, we provide a comprehensive update of the subsequent 1.5 years, employing the joint expertise of the IMIGC to systematically evaluate all available evidence (as of 1 July 2020) for monogenic causes of isolated or syndromic male infertility, endocrine disorders or reproductive system abnormalities affecting the male sex organs. In addition, we systematically assessed the evidence for all previously reported possible monogenic causes of male infertility, using a framework designed for a more appropriate clinical interpretation of disease genes.Search Methods: We performed a literature search according to the PRISMA guidelines up until 1 July 2020 for publications in English, using search terms related to 'male infertility' in combination with the word 'genetics' in PubMed. Next, the quality and the extent of all evidence supporting selected genes were assessed using an established and standardised scoring method. We assessed the experimental quality, patient phenotype assessment and functional evidence based on gene expression, mutant in-vitro cell and in-vivo animal model phenotypes. A final score was used to determine the clinical validity of each GDR, across the following five categories: no evidence, limited, moderate, strong or definitive. Variants were also reclassified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines and were recorded in spreadsheets for each GDR, which are available at imigc.org.Outcomes: The primary outcome of this review was an overview of all known GDRs for monogenic causes of human male infertility and their clinical validity. We identified a total of 120 genes that were moderately, strongly or definitively linked to 104 infertility phenotypes.Wider Implications: Our systematic review curates all currently available evidence to reveal the strength of GDRs in male infertility. The existing guidelines for genetic testing in male infertility cases are based on studies published 25 years ago, and an update is far overdue. The identification of 104 high-probability 'human male infertility genes' is a 33% increase from the number identified in 2019. The insights generated in the current review will provide the impetus for an update of existing guidelines, will inform novel evidence-based genetic testing strategies used in clinics, and will identify gaps in our knowledge of male infertility genetics. We discuss the relevant international guidelines regarding research related to gene discovery and provide specific recommendations to the field of male infertility. Based on our findings, the IMIGC consortium recommend several updates to the genetic testing standards currently employed in the field of human male infertility, most important being the adoption of exome sequencing, or at least sequencing of the genes validated in this study, and expanding the patient groups for which genetic testing is recommended. [ABSTRACT FROM AUTHOR]

Background: Spermatozoa acquire their motility and fertilizing abilities during their maturation through the epididymis. This process is controlled by epididymal epithelial cells that possess features adapted to sense and respond to their surrounding environment and to communicate with spermatozoa. During the past decade, new intercellular communication processes have been discovered, including the secretion and transport of molecules from the epithelium to spermatozoa via extracellular vesicles (EVs), as well as sensing of the intraluminal milieu by cellular extensions.Objective and Rationale: This review addresses recent findings regarding epididymal epithelial cell features and interactions between spermatozoa and the epididymal epithelium as well as epigenetic modifications undergone by spermatozoa during transit through the epididymal microenvironment.Search Methods: A systematic search was conducted in Pubmed with the keyword 'epididymis'. Results were filtered on original research articles published from 2009 to 2021 and written in the English language. One hundred fifteen original articles presenting recent advancements on the epididymis contribution to sperm maturation were selected. Some additional papers cited in the primary reference were also included. A special focus was given to higher mammalian species, particularly rodents, bovines and humans, that are the most studied in this field.Outcomes: This review provides novel insights into the contribution of epididymal epithelium and EVs to post-testicular sperm maturation. First, new immune cell populations have been described in the epididymis, where they are proposed to play a role in protecting the environment surrounding sperm against infections or autoimmune responses. Second, novel epididymal cell extensions, including dendrites, axopodia and primary cilia, have been identified as sensors of the environment surrounding sperm. Third, new functions have been outlined for epididymal EVs, which modify the sperm epigenetic profile and participate in transgenerational epigenetic inheritance of paternal traits.Wider Implications: Although the majority of these findings result from studies in rodents, this fundamental research will ultimately improve our knowledge of human reproductive physiopathologies. Recent discoveries linking sperm epigenetic modifications with paternal environmental exposure and progeny outcome further stress the importance of advancing fundamental research on the epididymis. From this, new therapeutic options for infertile couples and better counseling strategies may arise to increase positive health outcomes in children conceived either naturally or with ART. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the prevalence of obesity in women of reproductive age is increasing. Bariatric surgery is currently viewed as the most effective, long-term solution for this problem. Preconception bariatric surgery can reduce the prevalence of obesity-related subfertility and adverse maternal, pregnancy and birth outcomes. Maternal health during the periconception period is crucial for optimal gametogenesis and for embryonic and fetal development which also affects health in the later lives of both mother and offspring. Although preconception bariatric surgery improves several pregnancy outcomes, it can also increase the prevalence of pregnancy complications due to excessive and rapid weight loss. This can lead to iatrogenic malnutrition with vitamin deficiencies and derangements in metabolic and endocrine homeostasis. Thus, bariatric surgery can greatly influence periconception maternal health with consequences for reproduction, pregnancy and health in later life. However, its influence on periconception maternal health itself has never been reviewed systematically.Objective and Rationale: The aim of this review was to investigate associations between bariatric surgery and determinants of periconception maternal health such as endocrine changes, fertility, vitamin status, irregular menstrual cycles, miscarriages and congenital malformations.Search Methods: Medline, Embase, PubMed, Web of Science, Google Scholar and the Cochrane databases were used for the literature search until 1 November 2020. The search strategy terms included, among others, bariatric surgery, hormones, fertility, malformations, miscarriages and vitamin status. We searched for human studies that were written in English. Abstracts, reviews, meta-analyses and conference papers were excluded. The ErasmusAGE score was used to assess the quality of the included studies.Outcomes: A total of 51 articles were analysed. The mean quality score was 5 (range 2-8). After bariatric surgery, hormonal axes normalized and menstrual cycle regularity was restored, resulting in increased fertility. Overall, there were no short-term risks for reproductive outcomes such as the increased risk of miscarriages or congenital malformations. However, the risk of vitamin deficiencies was generally increased after bariatric surgery. A meta-analysis of 20 studies showed a significant decrease in infertility (risk difference (RD) -0.24, 95% confidence interval (CI) -0.42, -0.05) and menstrual cycle irregularities (RD -0.24, 95% CI -0.34, -0.15) with no difference in rates of miscarriage (RD 0.00, 95% CI -0.09, 0.10) and congenital malformations (RD 0.01, 95% CI -0.02, 0.03).Wider Implications: The current systematic review and meta-analysis show associations between bariatric surgery and periconception maternal health and underlines the need for providing and personalizing preconception care for women after bariatric surgery. We recommend preconception care including the recommendation of postponing pregnancy until weight loss has stabilized, irrespective of the surgery-to-pregnancy interval, and until vitamin status is normalized. Therefore, regular monitoring of vitamin status and vitamin supplementation to restore deficiencies is recommended. Furthermore, this systematic review emphasizes the need for a long-term follow-up research of these women from the periconception period onwards as well as their pregnancies and offspring, to further improve care and outcomes of these mothers and children. [ABSTRACT FROM AUTHOR]

Background: Stanniocalcin-1 (STC-1) is a widely expressed glycoprotein hormone involved in a diverse spectrum of physiological and pathophysiological processes including angiogenesis, mineral homeostasis, cell proliferation, inflammation and apoptosis. Over the last 20 years, numerous studies have reported STC-1 expression within female reproductive tissues including the uterus, ovaries and placenta and implicated STC-1 in processes such as ovarian follicular development, blastocyst implantation, vascular remodelling in early pregnancy and placental development. Notably, dysregulation of STC-1 within reproductive tissues has been linked to the onset of severe reproductive disorders including endometriosis, polycystic ovary syndrome, poor trophoblast invasion and placental perfusion in early pregnancy. Furthermore, significant changes in tissue expression and in maternal systemic concentration take place throughout pregnancy and further substantiate the vital role of this protein in reproductive health and disease.Objective and Rationale: Our aim is to provide a comprehensive overview of the existing literature, to summarise the expression profile and roles of STC-1 within the female reproductive system and its associated pathologies. We highlight the gaps in the current knowledge and suggest potential avenues for future research.Search Methods: Relevant studies were identified through searching the PubMed database using the following search terms: 'stanniocalcin-1', 'placenta', 'ovary', 'endometrium', 'pregnancy', 'reproduction', 'early gestation'. Only English language papers published between 1995 and 2020 were included.Outcomes: This review provides compelling evidence of the vital function that STC-1 plays within the female reproductive system. The literature presented summarise the wide expression profile of STC-1 within female reproductive organs, as well as highlighting the putative roles of STC-1 in various functions in the reproductive system. Moreover, the observed link between altered STC-1 expression and the onset of various reproductive pathologies is presented, including those in pregnancy whose aetiology occurs in the first trimester. This summary emphasises the requirement for further studies on the mechanisms underlying the regulation of STC-1 expression and function.Wider Implications: STC-1 is a pleiotropic hormone involved in the regulation of a number of important biological functions needed to maintain female reproductive health. There is also growing evidence that dysregulation of STC-1 is implicated in common reproductive and obstetric disorders. Greater understanding of the physiology and biochemistry of STC-1 within the field may therefore identify possible targets for therapeutic intervention and/or diagnosis. [ABSTRACT FROM AUTHOR]

Comments on the progress in nicotine research. Development of experimental models for the study of the various component processes of nicotine dependence; Difficulties in sustaining treatment gains for drug dependence in general; Usefulness of biological and behavioral studies in understanding the acquisition of tobacco-use behavior.

Background: Rigorously designed longitudinal studies can inform how best to reduce the widening health gap between Indigenous and non-Indigenous children.Methods: A systematic review was performed to identify and present the breadth and depth of longitudinal studies reporting the health and well-being of Indigenous children (aged 0-18 years) globally. Databases were searched up to 23 June 2020. Study characteristics were mapped according to domains of the life course model of health. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools. Reported level of Indigenous involvement was also appraised; PROSPERO registration CRD42018089950.Results: From 5545 citations, 380 eligible papers were included for analysis, representing 210 individual studies. Of these, 41% were located in Australia (n = 88), 22.8% in the USA (n = 42), 11.9% in Canada (n = 25) and 10.9% in New Zealand (n = 23). Research tended to focus on either health outcomes (50.9%) or health-risk exposures (43.8%); 55% of studies were graded as 'good' quality; and 89% of studies made at least one reference to the involvement of Indigenous peoples over the course of their research.Conclusions: We identified gaps in the longitudinal assessment of cultural factors influencing Indigenous child health at the macrosocial level, including connection to culture and country, intergenerational trauma, and racism or discrimination. Future longitudinal research needs to be conducted with strong Indigenous leadership and participation including holistic concepts of health. This is critical if we are to better understand the systematic factors driving health inequities experienced by Indigenous children globally. [ABSTRACT FROM AUTHOR]

Introduction: Smokeless tobacco (ST) is a significant South Asian public health problem. This paper reports a qualitative study of a sample of South Asian ST users.Methods: Interviews, using a piloted topic guide, with 33 consenting, urban dwelling adult ST users explored their ST initiation, continued use, and cessation attempts. Framework data analysis was used to analyze country specific data before a thematic cross-country synthesis was completed.Results: Participants reported long-term ST use and high dependency. All reported strong cessation motivation and multiple failed attempts because of ease of purchasing ST, tobacco dependency, and lack of institutional support.Conclusions: Interventions to support cessation attempts among consumers of South Asian ST products should address the multiple challenges of developing an integrated ST policy, including cessation services.Implications: This study provides detailed understanding of the barriers and drivers to ST initiation, use, and cessation for users in Bangladesh, India, and Pakistan. It is the first study to directly compare these three countries. The insight was then used to adapt an existing behavioral support intervention for ST cessation for testing in these countries. [ABSTRACT FROM AUTHOR]

Introduction: Smoking rates are alarmingly high among young people experiencing homelessness (YEH), yet there are no evidence-based cessation programs for this population. This paper presents results from a pilot evaluation of a text messaging-based smoking cessation treatment, as an adjunct to brief group cessation counseling, to improve abstinence rates among 18-25-year-old smokers experiencing homelessness. The goal of this study was to estimate effect sizes for a larger trial and it was not powered to detect group differences.Aims and Methods: YEH smokers who had a working cell phone with them at recruitment were randomized to receive a group counseling session, nicotine patches, and written material on quitting (n = 37) or a similar program that also included a 6-week automated text messaging intervention (TMI) to provide ongoing support for quitting (n = 40). Smoking outcomes were evaluated through a 90-day follow-up.Results: Seven-day point prevalence abstinence at 90-day follow-up was higher in the TMI condition than standard condition (17.50% vs. 8.11%, respectively; Cohen's h = .37); however, the 90-day continuous abstinence rate was not statistically different from zero in either condition. Reductions in the number of days smoked in the past 30 days from baseline to follow-up were greater in the TMI condition than the standard condition (-14.24 vs. -8.62, respectively; Cohen's d = .49).Conclusions: Adding a 6-week TMI support to a brief group counseling and pharmacotherapy protocol holds promise for smoking reduction and abstinence among YEH smokers. Results indicate that further development and evaluation of the TMI in this population is warranted.Trial Registration: ClinicalTrials.gov Identifier NCT03874585. Registered March 14, 2019, https://clinicaltrials.gov/ct2/show/record/NCT03874585.Implications: This is the first study to evaluate the feasibility of using a text messaging-based intervention (TMI) for behavior change with 18-25 year olds experiencing homelessness, and more specifically, the first to test a TMI to provide ongoing support for smoking cessation. Small to medium effect sizes for the TMI are promising in terms of implementing a TMI using participants' own cell phones, as well as the efficacy of this approach as an adjunct to standard care (brief group counseling and pharmacotherapy) for smoking cessation among YEH. [ABSTRACT FROM AUTHOR]

In 2019, the National Institutes of Health combined the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) into the MACS/WIHS Combined Cohort Study (MWCCS). In this paper, participants who made a study visit during October 2018–September 2019 (targeted for MWCCS enrollment) are described by human immunodeficiency virus (HIV) serostatus and compared with people living with HIV (PLWH) in the United States. Participants include 2,115 women and 1,901 men with a median age of 56 years (interquartile range, 48–63); 62% are PLWH. Study sites encompass the South (18%), the Mid-Atlantic/Northeast (45%), the West Coast (22%), and the Midwest (15%). Participant race/ethnicity approximates that of PLWH throughout the United States. Longitudinal data and specimens collected for 35 years (men) and 25 years (women) were combined. Differences in data collection and coding were reviewed, and key risk factor and comorbidity data were harmonized. For example, recent use of alcohol (62%) and tobacco (28%) are common, as are dyslipidemia (64%), hypertension (56%), obesity (42%), mildly or severely impaired daily activities (31%), depressive symptoms (28%), and diabetes (22%). The MWCCS repository includes serum, plasma, peripheral blood mononuclear cells, cell pellets, urine, cervicovaginal lavage samples, oral samples, B-cell lines, stool, and semen specimens. Demographic differences between the MACS and WIHS can confound analyses by sex. The merged MWCCS is both an ongoing observational cohort study and a valuable resource for harmonized longitudinal data and specimens for HIV-related research. [ABSTRACT FROM AUTHOR]