170 research outputs found

    The Effects of Shoe Design on Lower Limb Running Kinematics

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    The preference of running as a form of exercise exposes more recreational athletes to the risk of injury. Stress fractures occur for 0.7-20% of all running injuries (Wilder & Sethi, 2004) and 24-50% of stress fractures occur in the tibia (Aweid, Aweid, Talibi, & Porter, 2013). Stress fractures have been associated with high vertical impact peaks while running (Willy & Davis, 2013) so methods such as barefoot running and minimalist shoes aim to reduce these impact peaks by enforcing a more forefoot running pattern. Shoes with a lower drop height have been shown to induce a more forefoot running pattern without the discomfort of running barefoot or in non-cushioned minimalist shoes (Horvais & Samozino, 2012). The purpose of this study was to compare ankle joint kinematics, dorsiflexor muscle activity, and tibial axial acceleration while wearing low and high heel-drop shoes. Six female participants (19.8(1.0) years, 163.0(3.8) cm, and 60.4(5.5) kg) who ran a minimum of 10 miles per week provided informed consent prior to testing. Participants were equipped with a 16g BioNomadix tri-axial accelerometer attached to the tibia, a Bi-axial electrogoniometer attached at the ankle, two Ag-AgCl surface electrodes attached to the tibialis anterior with adhesive discs, one reference electrode placed on the anteromedial aspect of the tibia (not above a muscle), and a heart rate monitor. Participants completed two data running trials at a target effort of 65-70% of the heart rate reserve. Trials were performed in different shoes (drop heights 4mm(S1) and 11.7mm(S2)) with a minimum 10-minute rest between trials. Paired t-tests were used to compare conditions for each variable. Mean ankle angles at ground contact (S1=100.9(3.8)°, S2=102.6(3.0)°) were not significantly different (t(5)=-1.465, p=0.203) and had a small effect size (Cohen d=0.598). Mean peak tibial accelerations (S1=5.22(2.51g), S2=5.90(2.90)g) were not significantly different (t(5)=-1.238, p=0.271) and had a small effect size (Cohen d=0.505). The mean percentages of maximal EMG for the tibialis anterior (S1=66.2(45.7)%, S2=55.6(38.5)%) were not significant (t(5)=1.380, p=0.226) and had a small effect size (Cohen d=0.563). Though differences were observed between shoe conditions for each participant, the shoe drop height did not significantly affect the measured variables and cannot be assumed to be responsible for these observed differences

    Gauging U.S. Emergency Medical Services Workers' Willingness to Respond to Pandemic Influenza Using a Threat- and Efficacy-Based Assessment Framework

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    Emergency Medical Services workers' willingness to report to duty in an influenza pandemic is essential to healthcare system surge amidst a global threat. Application of Witte's Extended Parallel Process Model (EPPM) has shown utility for revealing influences of perceived threat and efficacy on non-EMS public health providers' willingness to respond in an influenza pandemic. We thus propose using an EPPM-informed assessment of EMS workers' perspectives toward fulfilling their influenza pandemic response roles.We administered an EPPM-informed snapshot survey about attitudes and beliefs toward pandemic influenza response, to a nationally representative, stratified random sample of 1,537 U.S. EMS workers from May-June 2009 (overall response rate: 49%). Of the 586 respondents who met inclusion criteria (currently active EMS providers in primarily EMS response roles), 12% indicated they would not voluntarily report to duty in a pandemic influenza emergency if asked, 7% if required. A majority (52%) indicated their unwillingness to report to work if risk of disease transmission to family existed. Confidence in personal safety at work (OR = 3.3) and a high threat/high efficacy ("concerned and confident") EPPM profile (OR = 4.7) distinguished those who were more likely to voluntarily report to duty. Although 96% of EMS workers indicated that they would probably or definitely report to work if they were guaranteed a pandemic influenza vaccine, only 59% had received an influenza immunization in the preceding 12 months.EMS workers' response willingness gaps pose a substantial challenge to prehospital surge capacity in an influenza pandemic. "Concerned and confident" EMS workers are more than four times as likely to fulfill pandemic influenza response expectations. Confidence in workplace safety is a positively influential modifier of their response willingness. These findings can inform insights into interventions for enhancing EMS workers' willingness to respond in the face of a global infectious disease threat

    HTLV-1 clonality during chronic infection and BLV clonality during primary infection

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    peer reviewedaudience: researcherHTLV-1 clonality during chronic infection and BLV clonality during primary infection Nicolas A Gillet1,2*, Carol Hlela1, Tine Verdonck3, Eduardo Gotuzzo3, Daniel Clark3, Sabrina Rodriguez2, Nirav Malani4, Anat Melamed1, Niall Gormley5, Richard Carter5, David Bentley5, Charles Berry6, Frederic D Bushman4, Graham P Taylor7, Luc Willems2, Charles R M Bangham1 1Department of Immunology, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. 2Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, 4000, Belgium. 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 4Department of Microbiology, University of Pennsylvania School of Medicine, Pennsylvania, Philadelphia, PA, 19104, USA. 5Illumina, Chesterford Research Park, Essex, Little Chesterford, CB10 1XL, UK. 6University of California, California, La Jolla San Diego, CA, 92093-0901, USA. 7Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the abundance of HTLV-1-infected clones remain unknown. We demonstrate that negative selection dominates during chronic infection, favouring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We postulated that this selection occurred mainly during the primary infection. We are testing this hypothesis in an animal model by studying the BLV clonality during the primary infection in cows. By measuring the proviral load, the anti-BLV immune response and the BLV clonality we aim to quantify the impact of the immune response on the rate of infectious spread and on the selection of proviruses inserted in a particular genomic environment. Co-infection with Strongyloides stercoralis or Staphylococcus appears to be another risk factor for the development of HTLV-1 associated diseases. We observed that HTLV-1 clonality is altered by co-infection with these pathogens with an increase of both the number and the abundance of the infected T-cell clones. The genomic characteristics of the proviral integration sites in the most abundant clones differ significantly between co-infected individuals and those with HTLV-1 alone, implying the existence of different selection forces in co-infected patients. The rate of appearance of new clones in patients co-infected with Strongyloides stercoralis is higher than in patients with HTLV-1 alone. By comparing skin lesions and blood samples from patients with Infective Dermatitis associated with HTLV-1 (IDH), we observed a significant proportion of distinct infected clones between the two compartments. The skin lesions seem to be a site for HTLV-1 infectious spread

    High-throughput, quantitative analyses of genetic interactions in E. coli.

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    Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

    Flow of the West Antarctic Ice Sheet on the continental margin of the Bellingshausen Sea at the Last Glacial Maximum

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    Geophysical data show that during the last glaciation the West Antarctic Ice Sheet (WAIS) drained to the continental shelf edge of the Bellingshausen Sea through a cross-shelf bathymetric trough (Belgica Trough) as a grounded, fast flowing, ice stream. The drainage basin feeding this ice stream probably encompassed southwestern Palmer Land, parts of southern Alexander Island, and the Bryan Coast of Ellsworth Land, with an area exceeding 200,000 km2. On the inner continental shelf, streamlined bedrock and drumlins mapped by swath bathymetry show that the ice stream was fed by convergent ice flow draining from Eltanin Bay and bays to the east, as well as by ice draining the southern part of the Antarctic Peninsula Ice Sheet through the Ronne Entrance. The presence of a paleoice stream in Belgica Trough is indicated by megascale glacial lineations formed in soft till and a trough mouth fan on the continental margin. Grounding zone wedges on the inner and midshelf record ice marginal stillstands during deglaciation and imply a staggered pattern of ice sheet retreat. These new data indicate an extensive WAIS at the Last Glacial Maximum (LGM) on the Bellingshausen Sea continental margin, which advanced to the shelf edge. In conjunction with ice sheet reconstructions from the Antarctic Peninsula and Pine Island Bay, this implies a regionally extensive ice sheet configuration during the LGM along the Antarctic Peninsula, Bellingshausen Sea, and Amundsen Sea margins, with fast flowing ice streams draining the WAIS and Antarctic Peninsula Ice Sheet to the continental shelf edge

    The Evolution of the DLK1-DIO3 Imprinted Domain in Mammals

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    A comprehensive, domain-wide comparative analysis of genomic imprinting between mammals that imprint and those that do not can provide valuable information about how and why imprinting evolved. The imprinting status, DNA methylation, and genomic landscape of the Dlk1-Dio3 cluster were determined in eutherian, metatherian, and prototherian mammals including tammar wallaby and platypus. Imprinting across the whole domain evolved after the divergence of eutherian from marsupial mammals and in eutherians is under strong purifying selection. The marsupial locus at 1.6 megabases, is double that of eutherians due to the accumulation of LINE repeats. Comparative sequence analysis of the domain in seven vertebrates determined evolutionary conserved regions common to particular sub-groups and to all vertebrates. The emergence of Dlk1-Dio3 imprinting in eutherians has occurred on the maternally inherited chromosome and is associated with region-specific resistance to expansion by repetitive elements and the local introduction of noncoding transcripts including microRNAs and C/D small nucleolar RNAs. A recent mammal-specific retrotransposition event led to the formation of a completely new gene only in the eutherian domain, which may have driven imprinting at the cluster

    Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure

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    OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP).METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses.RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction &lt; 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings.</p

    The Plant Pathogen Pseudomonas syringae pv. tomato Is Genetically Monomorphic and under Strong Selection to Evade Tomato Immunity

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    Recently, genome sequencing of many isolates of genetically monomorphic bacterial human pathogens has given new insights into pathogen microevolution and phylogeography. Here, we report a genome-based micro-evolutionary study of a bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations were identified between five sequenced isolates in 3,543,009 nt of analyzed genome sequence, which suggests a recent evolutionary origin of this pathogen. Further analysis with genome-derived markers of 89 world-wide isolates showed that several genotypes exist in North America and in Europe indicating frequent pathogen movement between these world regions. Genome-derived markers and molecular analyses of key pathogen loci important for virulence and motility both suggest ongoing adaptation to the tomato host. A mutational hotspot was found in the type III-secreted effector gene hopM1. These mutations abolish the cell death triggering activity of the full-length protein indicating strong selection for loss of function of this effector, which was previously considered a virulence factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed identifying a new microbe associated molecular pattern (MAMP) in a region distinct from the known MAMP flg22. Interestingly, the ancestral allele of this MAMP induces a stronger tomato immune response than the derived alleles. The ancestral allele has largely disappeared from today's Pto populations suggesting that flagellin-triggered immunity limits pathogen fitness even in highly virulent pathogens. An additional non-synonymous mutation was identified in flg22 in South American isolates. Therefore, MAMPs are more variable than expected differing even between otherwise almost identical isolates of the same pathogen strain
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