46 research outputs found

    THE EFFECT OF A PHYSICAL EDUCATION GAMES UNIT ON CHILDREN’S PARTICIPATION IN NEIGHBORHOOD PHYSICAL ACTIVITY

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    Many strategies to increase children’s physical activity have been studied, noted and implemented. It is important that physical educators realize their role in increasing physical activity both in school and outside of school. In order to promote physical activity outside of school it is important to understand what types of physical activities in which children enjoy participating. This study manipulated specific games taught in physical education classes and then explored how many and what types of these activities were continued in out-of-school free play at home in the children’s neighborhood. The students’ activities increased after the intervention, especially the activities taught in the Physical Education class. Activities tended to take place closer to their homes and required little to no equipment. A majority of students enjoyed playing outside for at least one hour per day. A pre and post 7-day activity survey showed activity frequency increased after a games unit was taught in physical education class

    Surveillance for Anthrax Cases Associated with Contaminated Letters, New Jersey, Delaware, and Pennsylvania, 2001

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    In October 2001, two inhalational anthrax and four cutaneous anthrax cases, resulting from the processing of Bacillus anthracis–containing envelopes at a New Jersey mail facility, were identified. Subsequently, we initiated stimulated passive hospital-based and enhanced passive surveillance for anthrax-compatible syndromes. From October 24 to December 17, 2001, hospitals reported 240,160 visits and 7,109 intensive-care unit admissions in the surveillance area (population 6.7 million persons). Following a change to reporting criteria on November 8, the average of possible inhalational anthrax reports decreased 83% from 18 to 3 per day; the proportion of reports requiring follow-up increased from 37% (105/286) to 41% (47/116). Clinical follow-up was conducted on 214 of 464 possible inhalational anthrax patients and 98 possible cutaneous anthrax patients; 49 had additional laboratory testing. No additional cases were identified. To verify the limited scope of the outbreak, surveillance was essential, though labor-intensive. The flexibility of the system allowed interim evaluation, thus improving surveillance efficiency

    The Chemotactic Defect in Wiskott-Aldrich Syndrome Macrophages Is Due to the Reduced Persistence of Directional Protrusions

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    Wiskott-Aldrich syndrome protein (WASp) is an actin nucleation promoting factor that is required for macrophages to directionally migrate towards various chemoattractants. The chemotaxis defect of WASp-deficient cells and its activation by Cdc42 in vivo suggest that WASp plays a role in directional sensing, however, its precise role in macrophage chemotaxis is still unclear. Using shRNA-mediated downregulation of WASp in the murine monocyte/macrophage cell line RAW/LR5 (shWASp), we found that WASp was responsible for the initial wave of actin polymerization in response to global stimulation with CSF-1, which in Dictyostelium discoideum amoebae and carcinoma cells has been correlated with the ability to migrate towards chemoattractants. Real-time monitoring of shWASp cells, as well as WASp−/− bone marrow-derived macrophages (BMMs), in response to a CSF-1 gradient revealed that the protrusions from WASp-deficient cells were directional, showing intact directional sensing. However, the protrusions from WASp-deficient cells demonstrated reduced persistence compared to their respective control shRNA and wild-type cells. Further examination showed that tyrosine phosphorylation of WASp was required for both the first wave of actin polymerization following global CSF-1 stimulation and proper directional responses towards CSF-1. Importantly, the PI3K, Rac1 and WAVE2 proteins were incorporated normally in CSF-1 – elicited protrusions in the absence of WASp, suggesting that membrane protrusion driven by the WAVE2 complex signaling is intact. Collectively, these results suggest that WASp and its phosphorylation play critical roles in coordinating the actin cytoskeleton rearrangements necessary for the persistence of protrusions required for directional migration of macrophages towards CSF-1

    Snapshot of the Eukaryotic Gene Expression in Muskoxen Rumen—A Metatranscriptomic Approach

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    BACKGROUND: Herbivores rely on digestive tract lignocellulolytic microorganisms, including bacteria, fungi and protozoa, to derive energy and carbon from plant cell wall polysaccharides. Culture independent metagenomic studies have been used to reveal the genetic content of the bacterial species within gut microbiomes. However, the nature of the genes encoded by eukaryotic protozoa and fungi within these environments has not been explored using metagenomic or metatranscriptomic approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a metatranscriptomic approach was used to investigate the functional diversity of the eukaryotic microorganisms within the rumen of muskoxen (Ovibos moschatus), with a focus on plant cell wall degrading enzymes. Polyadenylated RNA (mRNA) was sequenced on the Illumina Genome Analyzer II system and 2.8 gigabases of sequences were obtained and 59129 contigs assembled. Plant cell wall degrading enzyme modules including glycoside hydrolases, carbohydrate esterases and polysaccharide lyases were identified from over 2500 contigs. These included a number of glycoside hydrolase family 6 (GH6), GH48 and swollenin modules, which have rarely been described in previous gut metagenomic studies. CONCLUSIONS/SIGNIFICANCE: The muskoxen rumen metatranscriptome demonstrates a much higher percentage of cellulase enzyme discovery and an 8.7x higher rate of total carbohydrate active enzyme discovery per gigabase of sequence than previous rumen metagenomes. This study provides a snapshot of eukaryotic gene expression in the muskoxen rumen, and identifies a number of candidate genes coding for potentially valuable lignocellulolytic enzymes

    An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

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    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

    Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

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    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    Oral history interview with Beth Eddy

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    Transcript, 33 pp.Beth Eddy grew up in rural New York state then graduated with a math degree from Elmhurst College (outside Chicago). She accepted a job in 1966 at Western Electric working on the pioneering ESS, initially in downtown Chicago and then relocating to the Bell Labs Indian Hill facility in Naperville. Her work involved assembly or machine language programming, eventually COBOL, supporting large databases for the ESS project. After three years, she moved into installation engineering for ESS. She describes tactics for women’s “voice” to be effectively heard in meetings. She led a protest against a men-only ‘Stag Picnic’ (described also in Lois Herr’s Women, Power and AT&T [2002]). With a promotion to department chief, she became the earliest women in Western Electric management. To achieve salary parity, she arranged a transfer to AT&T headquarters and worked in maintenance engineering, another male-dominated area, returning to Indian Hill (around 1980) as assistant manager of the data center and a development group. She then took on supervisory positions in Human Relations, building construction, software development, and switching installation. She discusses strategies for attracting women and African-American staff as well as managing a diverse workforce. She shares observations on the 1970s women’s movement and its subsequent evolution. This material is based on work funded by the Alfred P. Sloan Foundation award B2014-07 “Tripling Women’s Participation in Computing (1965-1985).”Alfred P. Sloan Foundation award B2014-07 “Tripling Women’s Participation in Computing (1965-1985).

    The Third Sector and the State in England

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    Third sector organisations and the state have sought to work together in England since the inception of the welfare state, yet rarely has there been greater debate about this relationship than at present. Successive governments have sought to redefine the dominant pattern, with the policy focus moving from more ad hoc relationships to an (expressed) commitment to partnership and, more recently, to a push towards relatively passive delivery of state contracts. This paper maps the sector, charts this changing relationship and explores key areas of debate: the role of charitable organisations in the English policy environment, the importance of scale with regards to relations between state and sector; and the impact of commissioning in recent years. We conclude by considering the potential implication of change for the distinctiveness of the third sector
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