Menstrual hygiene management in schools: midway progress update on the “MHM in Ten” 2014–2024 global agenda

Progress has been made in recent years to bring attention to the challenges faced by school-aged girls around managing menstruation in educational settings that lack adequate physical environments and social support in low- and middle-income countries. To enable more synergistic and sustained progress on addressing menstruation-related needs while in school, an effort was undertaken in 2014 to map out a vision, priorities, and a ten-year agenda for transforming girls’ experiences, referred to as Menstrual Hygiene Management in Ten (MHM in Ten). The overarching vision is that girls have the information, support, and enabling school environment for managing menstruation with dignity, safety and comfort by 2024. This requires improved research evidence and translation for impactful national level policies. As 2019 marked the midway point, we assessed progress made on the five key priorities, and remaining work to be done, through global outreach to the growing network of academics, non-governmental organizations, advocates, social entrepreneurs, United Nations agencies, donors, and national governments. This paper delineates the key insights to inform and support the growing MHM commitment globally to maximize progress to reach our vision by 2024. Corresponding to the five priorities, we found that (priority 1) the evidence base for MHM in schools has strengthened considerably, (priority 2) global guidelines for MHM in schools have yet to be created, and (priority 3) numerous evidence-based advocacy platforms have emerged to support MHM efforts. We also identified (priority 4) a growing engagement, responsibility, and ownership of MHM in schools among governments globally, and that although MHM is beginning to be integrated into country-level education systems (priority 5), resources are lacking. Overall, progress is being made against identified priorities. We provide recommendations for advancing the MHM in Ten agenda. This includes continued building of the evidence, and expanding the number of countries with national level policies and the requisite funding and capacity to truly transform schools for all students and teachers who menstruate

Menstrual hygiene management in schools: midway progress update on the "MHM in Ten" 2014-2024 global agenda.

Progress has been made in recent years to bring attention to the challenges faced by school-aged girls around managing menstruation in educational settings that lack adequate physical environments and social support in low- and middle-income countries. To enable more synergistic and sustained progress on addressing menstruation-related needs while in school, an effort was undertaken in 2014 to map out a vision, priorities, and a ten-year agenda for transforming girls' experiences, referred to as Menstrual Hygiene Management in Ten (MHM in Ten). The overarching vision is that girls have the information, support, and enabling school environment for managing menstruation with dignity, safety and comfort by 2024. This requires improved research evidence and translation for impactful national level policies. As 2019 marked the midway point, we assessed progress made on the five key priorities, and remaining work to be done, through global outreach to the growing network of academics, non-governmental organizations, advocates, social entrepreneurs, United Nations agencies, donors, and national governments. This paper delineates the key insights to inform and support the growing MHM commitment globally to maximize progress to reach our vision by 2024. Corresponding to the five priorities, we found that (priority 1) the evidence base for MHM in schools has strengthened considerably, (priority 2) global guidelines for MHM in schools have yet to be created, and (priority 3) numerous evidence-based advocacy platforms have emerged to support MHM efforts. We also identified (priority 4) a growing engagement, responsibility, and ownership of MHM in schools among governments globally, and that although MHM is beginning to be integrated into country-level education systems (priority 5), resources are lacking. Overall, progress is being made against identified priorities. We provide recommendations for advancing the MHM in Ten agenda. This includes continued building of the evidence, and expanding the number of countries with national level policies and the requisite funding and capacity to truly transform schools for all students and teachers who menstruate

Brugia malayi Gene Expression in Response to the Targeting of the Wolbachia Endosymbiont by Tetracycline Treatment

Filarial parasites afflict hundreds of millions of individuals worldwide, and cause significant public health problems in many of the poorest countries in the world. Most of the human filarial parasite species, including Brugia malayi, harbor endosymbiotic bacteria of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female worm. The need exists for the development of new chemotherapeutic approaches that can practically exploit the vulnerability of the filaria to the loss of the Wolbachia. In this study we performed ultrastructural and microarray analyses of female worms collected from infected jirds treated with tetracycline. Results suggest that the endosymbiotic bacteria were specifically affected by the antibiotic. Furthermore, in response to the targeting of the endosymbiont, the parasites modulated expression of their genes. When exposed to tetracycline, the parasites over-expressed genes involved in protein synthesis. Expression of genes involved in cuticle biosynthesis and energy metabolism was, on the other hand, limited

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Stereotypic horses (Equus caballus) are not cognitively impaired

Stereotypies in animals are thought to arise from an interaction between genetic predisposition and sub-optimal housing conditions. In domestic horses, a well-studied stereotypy is crib-biting, an abnormal behaviour that appears to help individuals to cope with stressful situations. One prominent hypothesis states that animals affected by stereotypies are cognitively less flexible compared to healthy controls, due to sensitization of a specific brain area, the basal ganglia. The aim of this study was to test this hypothesis in crib-biting and healthy controls, using a cognitive task, reversal learning, which has been used as a diagnostic for basal ganglia dysfunction. The procedure consisted of exposing subjects to four learning tasks; first and second acquisition, and their reversals. For each task, we measured the number of trials to reach criterion and heart rate and heart-rate variability. Importantly, we did not try to prevent crib-biters from executing their stereotypic behaviour. We found that the first reversal learning task required the largest number of trials, confirming its challenging nature. Interestingly, the second reversal learning task required significantly fewer trials to reach criterion, suggesting generalisation learning. However, we did not find any performance differences across groups; both stereotypic and control animals required a similar numbers of trials and did not differ in their physiological responses. Our results thus challenge the widely held belief that crib-biting horses, and stereotypic animals more generally, are cognitively impaired. We conclude that cognitive underperformance may occur in stereotypic horses if they are prevented from crib-biting to cope with experienced stress.PostprintPeer reviewe

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Development of a dichotomous indicator for population-level assessment of dietary diversity in women of reproductive age

Background: Dietary diversity is a key element of diet quality, but diets of women of reproductive age (WRA; aged 15-49 y) in resource-poor settings are often deficient in a range of micronutrients. Previous work showed associations between simple food-group diversity indicators (FGIs) and micronutrient adequacy among WRA. For operational and advocacy purposes, however, there is strong demand for a dichotomous indicator reflecting an acceptable level of dietary diversity. Objective: The aim of the study was to develop a dichotomous indicator of dietary diversity inWRA. Methods: We performed a secondary analysis of 9 data sets containing quantitative dietary data from WRA in resource-poor settings (total n = 4166). From the raw dietary data, we calculated an individual "mean probability of adequacy" (MPA) across 11 micronutrients. Several candidate FGIs were constructed. Indicator performance in predicting an MPA > 0.60 was assessed within each data set by using receiver-operating characteristic analysis and sensitivity and specificity analysis at various FGI cutoffs. The analysis was performed separately for nonpregnant and nonlactating (NPNL) women and for lactating women. Results: We identified 2 "best candidate" dichotomous indicators on the basis of 9- or 10-point food-group scores (FGI-9 and FGI-10) with a cutoff of ≥ 5 food groups. Both were significantly correlated to MPA in each site (P < 0.001). Areas under the curve were moderate, ranging from 0.62 to 0.82 among NPNL women and from 0.56 to 0.90 among lactating women. Comparisons of results slightly favored FGI-10 for all women. Conclusions: When resource-intensive dietary methods are not feasible, a simple dichotomous indicator based on a cutoff of ≥ 5 of 10 defined food groups reflects "minimum dietary diversity for women of reproductive age." According to the conclusions of a consensus meeting of experts, this indicator is well suited for population-level assessment, advocacy, and possibly also for tracking of change in dietary diversity across time.</p

Non-animal methods to predict skin sensitization (II): an assessment of defined approaches^**

<p>Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple <i>in vitro</i> and <i>in chemico</i> skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain <i>in silico</i> predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating <i>in vitro, in chemico</i>, and <i>in silico</i> inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.</p