Highly contiguous assemblies of 101 drosophilid genomes

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Virtual Physical Education During COVID-19: Exploring Future Directions for Equitable Online Learning Tools

Introduction: School closures prompted by the COVID-19 pandemic reduced opportunities for US youth to be physically active and disproportionately impacted health disparities in this population. Physical education provides the largest intervention to support the physical activity of school-aged youth, but teachers' opinions about how to maintain quality programming during virtual learning periods remain unexplored. Applying a diversity, equity and inclusion framework, this study explored physical education teachers' perceived significance of different design features for an online teaching tool to promote physical activity equity during school closures. Methods: Previous literature and focus groups informed the development of a survey administered in summer/fall 2020. Survey participants ( n = 60) were physical education teachers from 400 randomly selected US preschool-12th grade schools drawing from a national database. Participants rated the significance of four design features in relation to five key attributes of an online supplement to in-person physical education programs. One-way ANOVAs were used to assess differences in teachers' ratings by demographic characteristics. Results: Between-group differences were found in teacher ratings of design features related to the usability, accessibility, equitability, and formal assessment capabilities of an online physical education tool. Differences were based on teacher gender, school level, and geographic location. Conclusions: Future research to promote physical activity equity among preschool-12th grade youth should examine tailored virtual physical education learning tools that address what teachers perceive to be the most significant design features to support equitable physical education among diverse student groups

Teaching on the Continuum: Epidemiology Education From High School Through Graduate School

Epidemiology education is increasingly recognized as a core science necessary for career preparation throughout the health sector, and graduate epidemiology instruction is continually being reevaluated to ensure students receive appropriate training. Recent work has also focused on the potential for epidemiology to be formally incorporated as a stand-alone discipline in undergraduate education and even integrated into wide-scale high-school science learning. As epidemiology educators, however, we face a tremendous challenge in that we should appreciate differences in students' instructional needs and goals (e.g., concepts and skills) at each educational level. In this article we propose an epidemiology learning continuum for students from high school through graduate school. We call for a student-centered instructional approach to best hone learners' grasp of concepts and skills. Furthermore, we propose scaffolded learning to help epidemiology students to develop more advanced insights and abilities as they progress in the field. This approach will not only best serve the discipline but also is well-aligned with the Association of Schools and Programs of Public Health's "Framing the Future" initiative for public health education for the 21st century

Physical fitness disparities among New York City public school youth using standardized methods, 2006-2017.

Standardized physical fitness monitoring provides a more accurate proxy for youth health when compared with physical activity. Little is known about the utilization of broad-scale individual-level youth physical fitness testing to explore health disparities. We examined longitudinal trends in population-level fitness for 4th-12th grade New York City youth during 2006/7-2016/17 (average n = 510,293 per year). Analyses were performed in 2019. The primary outcome was whether or not youth achieved sex-/age-specific performance levels (called the Healthy Fitness Zone) on the aerobic capacity, muscular strength and muscular endurance tests using the NYC FITNESSGRAM. The Cooper Institute's most recent Healthy Fitness Zone criteria were applied to all tests and years. Prevalence estimates were weighted, accounted for school clustering, adjusted for student-level sociodemographics, and run by sociodemographic subgroups and year. The overall prevalence for meeting 3 Healthy Fitness Zones increased from 15.5% (95%CI: 13.9%-17.0%) in 2006/7 to 23.3% (95%CI: 22.2%-24.4%) in 2016/17 for students in grades 4-12. Fitness for all student groups increased over time, although Hispanic and non-Hispanic black girls consistently had the lowest prevalence of meeting 3 Healthy Fitness Zones as compared to all other race/sex subgroups. Also, 9th-12th graders had a lower prevalence of meeting 3 Healthy Fitness Zones as compared to 4th-8th graders. Given forecasted sharp increases in cardiovascular disease prevalence, routine youth fitness surveillance using standardized, criterion referenced methods can identify important fitness disparities and inform interventions

Sex differences in fitness outcomes among minority youth after participation in a park-based after-school program

This study aimed to describe sex differences in fitness outcomes after participation in Fit2Play, a park-based after-school health and wellness program. Youth who participated in Fit2Play for either 1, 2, or 3 school years between 2010 and 2016 (n = 2129, mean age 9.1 years, 52% Hispanic, 48% non-Hispanic black, 54% male) were tested via a comprehensive fitness battery at the beginning/end of the school year(s). Effects of length of Fit2Play participation on fitness outcomes were assessed via three-level repeated measures analysis stratified by sex and adjusted for child sociodemographics, weight category, area poverty, and year. Significant improvements for boys and girls were found in the Progressive Aerobic Cardiovascular Endurance Run (P < .01 for girls, P < .001 for boys), 400 meter run tests (P < .001 for girls, P < .01 for boys), and push-ups (P < .01 for both), with dose-response trends for girls after up to 3 years of Fit2Play participation. From baseline to 1, 2, and 3 years of participation, girls demonstrated 8%, 14%, and 23% mean improvement in 400 meter run times versus 9%, 9%, and 17% for boys, respectively (P < .001 for all). Dose-response improvements were also found in girls for PACER scores and sit-ups. After-school physical activity programs can improve fitness in all youth, and particularly girls with increased years of participation. Further research should examine sex differences in the effects of park-/community-based programs to reduce sex disparities in fitness, particularly in light of the current youth obesity epidemic