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BACKGROUND: Hypercholesterolaemia and physical inactivity significantly contribute towards risk of coronary heart disease. Increased physical activity may be an effective way to improve lipid profiles in hypercholesterolaemic individuals. The aim of this study was to investigate whether a home-based physical activity program meeting current guidelines improved the lipid profile of hypercholesterolaemic men. METHODS: Sixty-seven hypercholesterolaemic men (55.1 (4.9) years), from Bristol England, recruited between 2002-2004, were randomized to either 12 weeks of brisk walking sufficient to expend at least 300 kcal each walk or control condition. Fasting lipids including total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, insulin, blood pressure and anthropometric characteristics were measured at baseline and follow-up. Compliance was monitored using accelerometers and activity logs. RESULTS: After controlling for baseline differences, TC/HDL-C was significantly lower in the intervention group at follow-up (-0.28, 95% CI: -0.52, -0.03, p=0.03). An increase in HDL-C (0.07 mmol/l: -0.01, 0.12, p=0.07) and reduction in TG (-0.30 mmol/l: -0.64, 0.03, p=0.07) in intervention participants were of borderline statistical significance. Weight significantly decreased in intervention participants (-1.40 kg: -2.43, -0.38, p<0.01). No other significant between group effects were found. Compliance to the walking program was 97.6%. CONCLUSIONS: Twelve weeks of moderate intensity walking was sufficient to improve TC/HDL-C in hypercholesterolaemic men, primarily through improvement in HDL-C. Copyright © 2008 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: The rising prevalence of obesity in children may be due to a reduction in physical activity (PA). OBJECTIVE: Our aim was to study the associations of objectively measured PA volume and its subcomponents with indicators of body fatness. DESIGN: A cross-sectional study of 1292 children aged 9-10 y from 4 distinct regions in Europe (Odense, Denmark; the island of Madeira, Portugal; Oslo; and Tartu, Estonia) was conducted. PA was measured by accelerometry, and indicators of body fatness were the sum of 5 skinfold thicknesses and body mass index (BMI; in kg/m(2)). We examined the associations between PA and body fatness by using general linear models adjusted for potential confounding variables. RESULTS: After adjustment for sex, study location, sexual maturity, birth weight, and parental BMI, time (min/d) spent at moderate and vigorous PA (P = 0.032) and time (min/d) spent at vigorous PA were significantly (P = 0.015) and independently associated with body fatness. Sex, study location, sexual maturity, birth weight, and parental BMI explained 29% (adjusted R(2) = 0.29) of the variation in body fatness. Time spent at vigorous PA explained an additional 0.5%. Children who accumulated <1 h of moderate PA/d were significantly fatter than were those who accumulated >2 h/d. CONCLUSIONS: The accumulated amount of time spent at moderate and vigorous PA is related to body fatness in children, but this relation is weak; the explained variance was <1%. Copyright © 2004 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Questionnaire surveys suggest physical activity levels in children are low, particularly among children from deprived areas. Using accelerometers, it was found that children from a deprived inner city school were active at recommended levels and had similar levels of activity to children in other studies from more affluent populations. However, this finding was dependent on the threshold used to define moderate activity. [ABSTRACT FROM AUTHOR]

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Bedient CE, Magrina JF, Noble BN, et al. Comparison of robotic and laparoscopic myomectomy. Am J Obstet Gynecol 2009;201:566.e1-5. [ABSTRACT FROM AUTHOR]

Background: Active travel is a possible method to increase physical activity in children, but the precise contribution of walking to school to daily physical activity is unclear.Purpose: To combine accelerometer and GPS data to quantify moderate-to-vigorous physical activity (MVPA) on the walk to and from school in relation to overall daily levels.Methods: Participants were 141 children aged 11-12 years from the PEACH Project (Personal and Environmental Associated with Children's Health) in Bristol, England, measured between 2008 and 2009. Eighty-four children met the inclusion criteria and were included in the final analysis. Accelerometers measured physical activity, GPS receivers recorded location, and mode of travel was self-reported. Data were analyzed between April and October 2011. Combined accelerometer and GPS data were mapped in a GIS. Minutes of MVPA were compared for school journeys taking place between 8:00 AM and 9:00 AM and between 3:00 PM and 5:00 PM and in relation to whole-day levels.Results: Physical activity levels during journeys to and from school were highly similar, and contributed 22.2 minutes (33.7%) of total daily MVPA. In addition, MVPA on the journey did not differ between boys and girls, but because girls have lower levels of daily physical activity than boys, the journey contributed a greater proportion of their daily MVPA (35.6% vs 31.3%).Conclusions: The journey to and from school is a significant contributor to MVPA in children aged 11-12 years. Combining GPS and accelerometer data within a GIS is a useful approach to quantifying specific journeys. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine whether the number of participants with multiple coronary heart disease (CHD) risk factors exceeded the number expected from a random distribution.Methods: A cross-sectional study of 1020 randomly selected boys and girls, 9 and 15 years old, was conducted. Risk factors were total cholesterol, HDL-cholesterol, triglyceride, serum insulin, and blood pressure. Physical fitness was assessed from a maximal cycle test and body fat from the sum of four skinfolds. Risk factors selected in the analysis were those related to the metabolic syndrome.Results: More participants than expected had four or five CHD risk factors. Four risk factors were found in 3.03 (95% confidence interval (CI): 2.24-4.10) times as many participants as expected from a random distribution and five risk factors were found in 8.70 (95% CI: 4.35-17.4) times as many participants as expected. Fifty (5.4%) had four or five risk factors and in these individuals physical fitness was 1.2 standard deviation (SD) lower and body mass index (BMI) 1.6 SD higher than mean values for the population.Conclusion: Clustering of risk factors for the metabolic syndrome was found in children and adolescents. Low levels of physical fitness and raised BMI in these individuals indicate that lifestyle factors such as physical activity and diet may influence the development of these unhealthy risk profiles. [ABSTRACT FROM AUTHOR]

There is substantial evidence for timing (time perception) abnormalities related to developmental disabilities, particularly autism spectrum disorder. These findings have been reported in humans and nonhuman preclinical models. Our research objective was to extend that work to a genetic knockout (KO) model of fragile X/developmental disability, the FMR1 KO rat. We also sought to test delay discounting in the model and assess potential relations between timing and choice behavior. Consistent with previous human and nonhuman work, we found reduced timing precision in the FMR1 KO rats. We also discovered significantly increased smaller, sooner reward choice in the FMR1 KO rats. Performance on the timing task appeared to be unrelated to performance on the choice task for both model and control rats. These results add to what has become increasingly clear: timing is disrupted in humans diagnosed with developmental disabilities and in nonhuman models designed to model developmental disabilities. Our findings are consistent with those of previous work and the first to our knowledge to show such effects in the FMR1 KO rat. We discuss the potential clinical implications and future directions surrounding potential "timing interventions" for individuals diagnosed with developmental disabilities., (© 2024 Society for the Experimental Analysis of Behavior.)

Background/objective: Atypical femur fractures (AFFs) caused by long-term bisphosphonate use are associated with high rates of delayed healing and nonunion., Case Report: A 64-year-old woman with osteopenia on alendronate for 15 years sustained a displaced left AFF following a fall from standing height. Imaging showed an acute displaced transverse diaphyseal left femur fracture with lateral cortical thickening and beaking. She underwent an open reduction and internal fixation with insertion of a cephalomedullary nail placed in compression mode, utilizing a novel technique involving intraoperative removal of the endosteal hypertrophied cortical bone at the fracture site. Alendronate was stopped and teriparatide was initiated postoperatively. Radiographs at 3.5 months postsurgery showed evidence of normal fracture union with mature callus formation., Discussion: AFFs caused by prolonged bisphosphonate use have a high rate of delayed healing and nonunion due to abnormal bone remodeling. Use of teriparatide postoperatively has been shown to reduce healing time in small observational studies in surgically treated patients. Our case demonstrates an expedited healing time of 3.5 months using teriparatide combined with a novel surgical technique involving removal of a portion of the abnormally remodeled bone and placement of an intramedullary nail in compression mode., Conclusion: Our case demonstrates an expedited healing time of 3.5 months compared to the average reported healing time for AFF of 10.7 months, supporting the use of the combination of teriparatide and a novel surgical technique., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 AACE. Published by Elsevier Inc.)

Introduction: Perinatal depression and anxiety cost the U.S. health system $102 million annually and result in adverse health outcomes. Research supports that cognitive behavioral therapy improves these conditions, but barriers to obtaining cognitive behavioral therapy have prevented its success in pregnant individuals. In this study, the impact of a cognitive behavioral therapy-based intervention on anxiety, depression, stress, healthy lifestyle beliefs, and behaviors in pregnant people was examined., Study Design: This study used a 2-arm RCT design, embedded in group prenatal care, with one arm receiving a cognitive behavioral therapy-based Creating Opportunities for Personal Empowerment program and the other receiving health promotion content., Setting/participants: Black and Hispanic participants (n=299) receiving prenatal care from 2018 to 2022 in New York and Ohio who screened high on 1 of 3 mental health measures were eligible to participate., Intervention: Participants were randomized into the manualized Creating Opportunities for Personal Empowerment cognitive behavioral therapy-based program, with cognitive behavioral skill-building activities delivered by advanced practice nurses in the obstetrical setting., Main Outcome Measures: Outcomes included anxiety, depression, and stress symptoms using valid and reliable tools (Generalized Anxiety Disorder scale, Edinburgh Postnatal Depression Scale, and Perceived Stress Scale). The Healthy Lifestyle Beliefs and Behaviors Scales examined beliefs about maintaining a healthy lifestyle and reported healthy behaviors., Results: There were no statistically significant differences between groups in anxiety, depression, stress, healthy beliefs, and behaviors. There were significant improvements in all measures over time. There were statistically significant decreases in anxiety, depression, and stress from baseline to intervention end, whereas healthy beliefs and behaviors significantly increased., Conclusions: Both cognitive behavioral therapy and health promotion content embedded in group prenatal care with advanced practice nurse delivery improved mental health and healthy lifestyle beliefs and behaviors at a time when perinatal mood generally worsens., Trial Registration: This study is registered with clinicaltrials.gov NCT03416010., (Copyright © 2024 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice ( n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance ( P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice ( P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice ( P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance. NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.

Circadian rhythms play a crucial role in the regulation of various physiological processes, including cardiovascular function and metabolism. Exercise provokes numerous beneficial adaptations in heart, including physiological hypertrophy, and serves to shift circadian rhythms. This study investigated the impact of time-restricted exercise training on exercise-induced adaptations in the heart and locomotor activity rhythms. Male mice (n = 45) were allocated to perform voluntary, time-restricted exercise in the early active phase (EAP), late active phase (LAP), or remain sedentary (SED) for 6 weeks. Subsequently, mice were allowed 24-h ad libitum access to the running wheel to assess diurnal rhythms in locomotor activity. Heart weight and cross-sectional area were measured at sacrifice, and cardiac protein and gene expression levels were assessed for markers of mitochondrial abundance and circadian clock gene expression. Mice rapidly adapted to wheel running, with EAP mice exhibiting a significantly greater running distance compared to LAP mice. Time-restricted exercise induced a shift in voluntary wheel activity during the 24-h free access period, with the acrophase in activity being significantly earlier in EAP mice compared to LAP mice. Gene expression analysis revealed a higher expression of Per1 in LAP mice. EAP exercise elicited greater cardiac hypertrophy compared to LAP exercise. These findings suggest that the timing of exercise affects myocardial adaptations, with exercise in the early active phase inducing hypertrophy in the heart. Understanding the time-of-day dependent response to exercise in the heart may have implications for optimizing exercise interventions for cardiovascular health., (© 2023. The Author(s).)

Objective: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy., Design: Analysis of data collected between 2017 and 2023., Setting: Multicenter., Patients: Patients of infertility treatment., Intervention: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result., Main Outcome Measures: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation., Results: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5)., Conclusion: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic., Competing Interests: Declaration of interests M.V. has nothing to disclose. E.G. has nothing to disclose. J.A.G. has nothing to disclose. M.M. has nothing to disclose. C.L. reports Patent application - Detection of structural aberrations in embryos, Patent application -Method for non-invasive preimplantation genetic diagnosis. M.C. has nothing to disclose. S.K. has nothing to disclose. P.Y. has nothing to disclose. N.K. has nothing to disclose. L.C. has nothing to disclose. A.B. has nothing to disclose. E.H.C. has nothing to disclose. C.Y.S. has nothing to disclose. M.S.L. has nothing to disclose. M.D.B. has nothing to disclose. A.R.C. reports honoraria from CooperSurgical and Ferring; leadership or board position Midwest Reproductive Society International, Sunfish, and Celmatix; stock Kindbody, Sunfish, Celmatix. Author Besser report honoraria from American Society for Reproductive Medicine, American College for Medical Genetics, Canadian Fertility and Andrology Society, Illinois Society of Genetic Professionals, Collaborative Group of the Americas on Inherited Colorectal Cancer, and National Society of Genetic Counselors; travel support from Collaborative Group of the Americas on Inherited Colorectal Cancer and American College for Medical Genetics; board member Genetic Counseling Professional Group (ASRM), Patient Education Committee (ASRM), International Registry of Mosaic Embryo Transfers. D.K.G. reports funding from Cooper Surgical and Igenomix for the submitted work; funding from Cooper Surgical; consulting fees from Care Fertility; honoraria from Ferring; payment for expert testimony; travel support from Ferring; Chair of International Chromosome and genome society; stock options from Conceivable outside the submitted work. D.Y.T. has nothing to disclose. F.L.B. has nothing to disclose. C.G.Z. has nothing to disclose. A.R.V. has nothing to disclose. A.G.B. has nothing to disclose. S.M. reports Patent application - Detection of structural aberrations in embryos, Patent application -Method for non-invasive preimplantation genetic diagnosis; Board Director – International Society for Preimplantation Diagnosis (PGDIS); Board Director – Canadian Fertility and Andrology Society (CFAS). F.S. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Fluvial fishes are threatened globally from intensive human landscape stressors degrading aquatic ecosystems. However, impacts vary regionally, as stressors and natural environmental factors differ between ecoregions and continents. To date, a comparison of fish responses to landscape stressors over continents is lacking, limiting understanding of consistency of impacts and hampering efficiencies in conserving fishes over large regions. This study addresses these shortcomings through a novel, integrative assessment of fluvial fishes throughout Europe and the conterminous United States. Using large-scale datasets, including information on fish assemblages from more than 30,000 locations on both continents, we identified threshold responses of fishes summarized by functional traits to landscape stressors including agriculture, pasture, urban area, road crossings, and human population density. After summarizing stressors by catchment unit (local and network) and constraining analyses by stream size (creeks vs. rivers), we analyzed stressor frequency (number of significant thresholds) and stressor severity (value of identified thresholds) within ecoregions across Europe and the United States. We document hundreds of responses of fish metrics to multi-scale stressors in ecoregions across two continents, providing rich findings to aid in understanding and comparing threats to fishes across the study regions. Collectively, we found that lithophilic species and, as expected, intolerant species are most sensitive to stressors in both continents, while migratory and rheophilic species are similarly strongly affected in the United States. Also, urban land use and human population density were most frequently associated with declines in fish assemblages, underscoring the pervasiveness of these stressors in both continents. This study offers an unprecedented comparison of landscape stressor effects on fluvial fishes in a consistent and comparable manner, supporting conservation of freshwater habitats in both continents and worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: A genetic etiology accounts for the majority of unexplained primary ovarian insufficiency (POI)., Objective: We hypothesized a genetic cause of POI for a sister pair with primary amenorrhea., Design: The study was an observational study. Subjects were recruited at an academic institution., Subjects: Subjects were sisters with primary amenorrhea caused by POI and their parents. Additional subjects included women with POI analyzed previously (n = 291). Controls were recruited for health in old age or were from the 1000 Genomes Project (total n = 233)., Intervention: We performed whole exome sequencing, and data were analyzed using the Pedigree Variant Annotation, Analysis and Search Tool, which identifies genes harboring pathogenic variants in families. We performed functional studies in a Drosophila melanogaster model., Main Outcome: Genes with rare pathogenic variants were identified., Results: The sisters carried compound heterozygous variants in DIS3. The sisters did not carry additional rare variants that were absent in publicly available datasets. DIS3 knockdown in the ovary of D. melanogaster resulted in lack of oocyte production and severe infertility., Conclusions: Compound heterozygous variants in highly conserved amino acids in DIS3 and failure of oocyte production in a functional model suggest that mutations in DIS3 cause POI. DIS3 is a 3' to 5' exoribonuclease that is the catalytic subunit of the exosome involved in RNA degradation and metabolism in the nucleus. The findings provide further evidence that mutations in genes important for transcription and translation are associated with POI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Type 2 diabetes mellitus (T2DM) and its associated complications puts considerable strain on healthcare systems. With the global incidence of T2DM increasing, effective disease management is essential. Physical activity (PA) is a key component of T2DM management; however, rates of PA engagement are low in this population. Developing effective and sustainable interventions that encourage PA is a high priority. Electrically assisted bicycles are becoming increasingly popular and may increase PA in healthy adults. This study aimed to provide evidence of the feasibility of conducting a randomized controlled trial to evaluate the efficacy of an e-cycling intervention to increase PA and improve health in individuals with T2DM., Methods: A parallel-group two-arm randomized, waitlist-controlled pilot study was conducted. Individuals were randomized to either an e-bike intervention or standard care. The intervention incorporated two one-to-one e-bike skills training and behavioural counselling sessions delivered by a community-based cycling charity, followed by a 12-week e-bike loan with two further sessions with the instructors. Feasibility was assessed via measures related to recruitment, retention and intervention implementation. Post-intervention interviews with instructors and participants explored the acceptability of the study procedures and intervention. Clinical, physiological and behavioural outcomes were collected at baseline and post-intervention to evaluate the intervention's potential., Results: Forty participants (M age  = 57) were randomized, of which 34 were recruited from primary care practices. Thirty-five participants were retained in the trial. The intervention was conducted with high fidelity (> 80% content delivered). E-bike training provided participants with the skills, knowledge and confidence needed to e-bike independently. Instructors reported being more confident delivering the skills training than behavioural counselling, despite acknowledging its importance. The study procedures were found to be acceptable to participants. Between-group differences in change during the intervention were indicative of the interventions potential for improving glucose control, health-related quality of life and cardiorespiratory fitness. Increases in overall device measured moderate-to-vigorous PA behaviour following the intervention were found, and there was evidence that this population self-selected to e-cycle at a moderate intensity., Conclusions: The study's recruitment, retention, acceptability and potential efficacy support the development of a definitive trial subject to identified refinements., Trial Registration: ISRCTN, ISRCTN67421464 . Registered 17/12/2018., (© 2023. The Author(s).)

Empathy is an important element of the social action, leadership, and transformation model for student leaders. Specifically, critical empathy is vital in developing group solidarity toward social-justice outcomes. In this article, we explain how we facilitate the development of critical empathy among student leaders in a co-curricular leadership development program., (© 2023 Wiley Periodicals, LLC.)

Purpose of Review: To discuss existing literature and current use of intravaginal culture (IVC) as an option for patients seeking fertility therapies., Recent Findings: IVC is the combination of oocytes and sperm with culture media in a sealed device that is placed vaginally and left in place while fertilization and early embryo development occurs. Studies show that IVC is safe, well-tolerated, and has similar outcomes in patients as compared to standard in vitro fertilization techniques (conventional insemination and/or intracytoplasmic sperm injection). The new device, INVOcell, while recommended by the FDA for minimal stimulation and up to 72 h of culture and seven oocytes, has been used successfully with more oocytes and for 5 days (until blastocyst stage for transfer) in many centers. Live birth rates and neonatal outcomes are reassuring., Summary: Infertility is a common disease and the vast majority of patients globally will not seek care. IVC may improve access to care, lower costs, provide an alternative for patients who have ethical or religious concerns, and be an increasingly utilized option for those seeking ART therapies. It may also ease workflow burdens in labs where space, equipment, or highly trained lab staff are scarce. More data is warranted to track cumulative outcomes and optimize the ideal patient candidate, but it is a viable alternative in the armamentarium of fertility therapies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Context: A genetic etiology likely accounts for the majority of unexplained primary ovarian insufficiency (POI)., Objective: We hypothesized that heterozygous rare variants and variants in enhanced categories are associated with POI., Design: The study was an observational study., Setting: Subjects were recruited at academic institutions., Patients: Subjects from Boston (n = 98), the National Institutes of Health and Washington University (n = 98), Pittsburgh (n = 20), Italy (n = 43), and France (n = 32) were diagnosed with POI (amenorrhea with an elevated follicle-stimulating hormone level). Controls were recruited for health in old age or were from the 1000 Genomes Project (total n = 233)., Intervention: We performed whole exome sequencing (WES), and data were analyzed using a rare variant scoring method and a Bayes factor-based framework for identifying genes harboring pathogenic variants. We performed functional studies on identified genes that were not previously implicated in POI in a D. melanogaster model., Main Outcome: Genes with rare pathogenic variants and gene sets with increased burden of deleterious variants were identified., Results: Candidate heterozygous variants were identified in known genes and genes with functional evidence. Gene sets with increased burden of deleterious alleles included the categories transcription and translation, DNA damage and repair, meiosis and cell division. Variants were found in novel genes from the enhanced categories. Functional evidence supported 7 new risk genes for POI (USP36, VCP, WDR33, PIWIL3, NPM2, LLGL1, and BOD1L1)., Conclusions: Candidate causative variants were identified through WES in women with POI. Aggregating clinical data and genetic risk with a categorical approach may expand the genetic architecture of heterozygous rare gene variants causing risk for POI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite increasing efforts globally to remove dams and construct fish passage structures, broad-scale analyses balancing tradeoffs between cost and habitat gains from these mitigations infrequently consider invasive species. We present an optimization-based approach for prioritizing dam mitigations to restore habitat connectivity for native fish species, while limiting invasive species spread. Our methodology is tested with a case study involving 240 dams in the Upper Mississippi River, USA. We integrate six native migratory fish species distribution models, distributions of two invasive fishes, and estimated costs for dam removal and construction of fish passes. Varying budgets and post-mitigation fish passage rates are analyzed for two scenarios: 'no invasives' where non-selective mitigations (e.g., dam removal) are used irrespective of potential invasive species habitat gains and 'invasives' where a mixture of selective (e.g., lift-and-sort fish passage) and non-selective mitigations are deployed to limit invasive species range expansion. To achieve the same overall habitat connectivity gains, we find that prioritizations accounting for invasive species are 3 to 6 times more costly than those that do not. Habitat gains among native fish species were highly variable based on potential habitat overlap with invasive species and post-mitigation passabilities, ranging from 0.4-58.9% ('invasives') and 7.9-95.6% ('no invasives') for a $50M USD budget. Despite challenges associated with ongoing nonnative fish invasions, opportunities still exist to restore connectivity for native species as indicated by individual dams being frequently selected in both scenarios across varying passabilities and budgets, however increased restoration costs associated with invasive species control indicates the importance of limiting their further spread within the basin. Given tradeoffs in managing for native vs. invasive species in river systems worldwide, our approach demonstrates strategies for identifying a portfolio of candidate barriers that can be investigated further for their potential to enhance native fish habitat connectivity while concurrently limiting invasive species dispersal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma., Design: Prospective cohort study., Setting: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada)., Patient(s): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization., Intervention(s): None., Main Outcome Measure(s): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count., Result(s): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4)., Conclusion(s): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible., (Copyright © 2021. Published by Elsevier Inc.)

Frequent and widespread testing of members of the population who are asymptomatic for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the mitigation of the transmission of the virus. Despite the recent increases in testing capacity, tests based on quantitative polymerase chain reaction (qPCR) assays cannot be easily deployed at the scale required for population-wide screening. Here, we show that next-generation sequencing of pooled samples tagged with sample-specific molecular barcodes enables the testing of thousands of nasal or saliva samples for SARS-CoV-2 RNA in a single run without the need for RNA extraction. The assay, which we named SwabSeq, incorporates a synthetic RNA standard that facilitates end-point quantification and the calling of true negatives, and that reduces the requirements for automation, purification and sample-to-sample normalization. We used SwabSeq to perform 80,000 tests, with an analytical sensitivity and specificity comparable to or better than traditional qPCR tests, in less than two months with turnaround times of less than 24 h. SwabSeq could be rapidly adapted for the detection of other pathogens., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Research Question: How do anti-Müllerian hormone (AMH) concentrations in women with and without arthritis compare? Is there an association between AMH and arthritis drug regimen?, Design: In this prospective cohort study, AMH was measured at two time points (T 0 and T 1 ) in 129 premenopausal women with arthritis. AMH at T 0 was compared with that from a bank of serum samples from 198 premenopausal women without arthritis. Primary outcomes were: (i) diminished ovarian reserve (DOR) (AMH <1.1 ng/ml) and (ii) annual rate of AMH decrease. Univariate, multivariable and Firth logistic regression identified variables associated with annual AMH decrease in excess of the 75th percentile., Results: Median time between T 0 and T 1 was 1.72 years. At time T 0 , median age-adjusted AMH in women with arthritis was significantly lower than that of women without arthritis (median 2.21 ng/ml versus 2.78 ng/ml; P = 0.009). Women with arthritis at highest risk for DOR had a history of tubal sterilization or were over the age of 35. Those with highest odds of having an annual AMH decrease in excess of the 75th percentile (over 28% decrease per year) were those: over the age of 35 or who sought care for infertility. Women with arthritis taking methotrexate alone (OR 0.08, 95% CI 0.01-0.67) or methotrexate plus tumour necrosis factor-alpha antagonists (OR 0.13, 95% CI 0.02-0.89) were less likely to be in the highest quartile of annual AMH decrease than women with arthritis not taking medication., Conclusions: Women with arthritis had lower AMH than healthy controls. Long-term methotrexate use was not associated with an annual AMH decrease., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to the high rates of transmission by individuals who are asymptomatic at the time of transmission 1,2 . Frequent, widespread testing of the asymptomatic population for SARS-CoV-2 is essential to suppress viral transmission. Despite increases in testing capacity, multiple challenges remain in deploying traditional reverse transcription and quantitative PCR (RT-qPCR) tests at the scale required for population screening of asymptomatic individuals. We have developed SwabSeq, a high-throughput testing platform for SARS-CoV-2 that uses next-generation sequencing as a readout. SwabSeq employs sample-specific molecular barcodes to enable thousands of samples to be combined and simultaneously analyzed for the presence or absence of SARS-CoV-2 in a single run. Importantly, SwabSeq incorporates an in vitro RNA standard that mimics the viral amplicon, but can be distinguished by sequencing. This standard allows for end-point rather than quantitative PCR, improves quantitation, reduces requirements for automation and sample-to-sample normalization, enables purification-free detection, and gives better ability to call true negatives. After setting up SwabSeq in a high-complexity CLIA laboratory, we performed more than 80,000 tests for COVID-19 in less than two months, confirming in a real world setting that SwabSeq inexpensively delivers highly sensitive and specific results at scale, with a turn-around of less than 24 hours. Our clinical laboratory uses SwabSeq to test both nasal and saliva samples without RNA extraction, while maintaining analytical sensitivity comparable to or better than traditional RT-qPCR tests. Moving forward, SwabSeq can rapidly scale up testing to mitigate devastating spread of novel pathogens.

Scalable, inexpensive, and secure testing for SARS-CoV-2 infection is crucial for control of the novel coronavirus pandemic. Recently developed highly multiplexed sequencing assays (HMSAs) that rely on high-throughput sequencing can, in principle, meet these demands, and present promising alternatives to currently used RT-qPCR-based tests. However, reliable analysis, interpretation, and clinical use of HMSAs requires overcoming several computational, statistical and engineering challenges. Using recently acquired experimental data, we present and validate a computational workflow based on kallisto and bustools, that utilizes robust statistical methods and fast, memory efficient algorithms, to quickly, accurately and reliably process high-throughput sequencing data. We show that our workflow is effective at processing data from all recently proposed SARS-CoV-2 sequencing based diagnostic tests, and is generally applicable to any diagnostic HMSA.

Introduction: Electrically assisted bicycles (e-bikes) have become increasingly popular in the past decade. This review aimed to scope the literature to identify what is known about the frequency and duration of e-bike use, their impact on travel behaviour, the purposes for which e-bikes are used and factors associated with e-bike use. In addition, the review aimed to identify gaps in the literature and highlight future research priorities., Methods: A scoping review of published and unpublished literature in any language. Relevant articles were identified through searching six databases, two grey literature platforms and reference lists. Searches were conducted until August 2019. Data were extracted using a standardised extraction form and descriptive and narrative results are provided., Results: Seventy-six studies met the inclusion criteria. The volume of research has increased since 2017 and primarily examines personal e-bike use, as opposed to e-bike share/rental schemes or organizational e-bike initiatives. The use of e-bikes increased the frequency and duration of cycling compared to conventional cycling and may help overcome barriers associated with conventional cycling. The uptake in e-cycling largely substitutes for conventional cycling or private car journeys, though the degree of substitution depends on the primary transport mode prior to e-bike acquisition. E-bikes are primarily used for utilitarian reasons, though older adults also engage in recreational e-cycling. Research priorities include quantitatively examining e-bike use, their impact on overall transport behaviour and identifying determinants of e-cycling to inform intervention and policy., Conclusions: This review suggests that the personal use of e-bikes is associated with a reduction in motorized vehicle use, which has potential positive impacts on the environment and health. The impacts of e-bike share schemes and workplace initiatives are less well understood. Evidence describing the purposes for which e-bikes are used, and the factors associated with usage, are useful to inform e-cycling promotion policy., Competing Interests: The authors declare that they have no competing interests., (© 2020 Elsevier Ltd. All rights reserved.)

The spatial pattern of flea (Siphonaptera: Pulicidae) infestation risk in cats and dogs across Great Britain is quantified, using data collected from a national survey undertaken in 2018, with particular attention given to the association between insecticidal treatment and infestation risk. Flea infestation risk declined significantly from south to north. None of the factors: pet breed, sex, neutered status or whether the pet had been abroad, showed any relationship with the underlying geographic distribution, which is most likely to be associated with climatic factors. However, overall, only 23.6% of the cats and 35% of the dogs inspected had been treated with identifiable flea products that were still 'in date' at the point of inspection. The percentage of owners treating their pet broadly followed infestation risk. The insecticide fipronil is a common active in a wide range of flea treatments and was the most frequently applied insecticide class, particularly in cats. However, 62% of cats and 45% of dogs that had been treated with a fipronil-based product that was 'in date' at the point of inspection still had fleas. Persistent flea infestation is likely to be due to a range of factors, including compliance and application failure, but the data provide strong inferential evidence for a lack of efficacy of fipronil-based products. Given the ubiquity of flea infestation, this finding and the relatively low-level of treatment compliance, highlight a clear need for greater owner education about the importance of flea management and a better understanding of the efficacy of different products., (© 2020 The Royal Entomological Society.)

Objective: To describe the current practice indications, methodology, and outcomes from a real-world experience of intravaginal culture (IVC) using INVOCELL., Design: A descriptive study outlining real-world experience with INVOCELL that addresses patient selection, ovarian stimulation, embryology laboratory practices, and outcomes., Setting: Five fertility centers in Missouri, Texas, North Carolina, South Carolina, and Virginia., Patients: Four hundred sixty-three patients undergoing 526 cycles., Intervention: IVC using INVOCELL., Main Outcome Measures: Cumulative pregnancy rate and live births. Secondary outcomes of interest included percent good quality embryos., Results: IVC with INVOCELL was primarily used in women <38 years with anti-Mullerian hormone level >0.8 ng/mL. The mean numbers of retrieved oocytes ranged from 9.2 to 16. Mean numbers of oocytes and sperm-injected oocytes loaded per INVOCELL ranged from a mean of 6.4-9.5 with a reported maximum of 34 oocytes loaded into the device. Most (95%) of the embryos were transferred on day 5. The mean blastocyst recovery per oocyte loaded into the device ranged from 19% to 34%; mean cumulative live birth plus ongoing pregnancy rates ranged from 29% to 53% per cycle start and 40% to 61% per transfer., Conclusions: This study of IVC using INVOCELL as an alternative model for infertility treatment confirms its utility as a viable alternative to standard incubator-based in vitro fertilization. The technology is compatible within the current framework of practice patterns and, when appropriately used, results in acceptable blastocyst recovery and live birth rates. Further use of INVOCELL in other clinical situations is warranted., (© 2020 The Authors.)