Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Comparison of deferral rates using a computerized versus written blood donor questionnaire: a randomized, cross-over study [ISRCTN84429599]

BACKGROUND: Self-administered computer-assisted blood donor screening strategies may elicit more accurate responses and improve the screening process. METHODS: Randomized crossover trial comparing responses to questions on a computerized hand-held tool (HealthQuiz, or HQ), to responses on the standard written instrument (Donor Health Assessment Questionnaire, or DHAQ). Randomly selected donors at 133 blood donation clinics in the area of Hamilton, Canada participated from 1995 to 1996. Donors were randomized to complete either the HQ or the DHAQ first, followed by the other instrument. In addition to responses of 'yes' and 'no' on both questionnaires, the HQ provided a response option of 'not sure'. The primary outcome was the number of additional donors deferred by the HQ. RESULTS: A total of 1239 donors participated. Seventy-one potential donors were deferred as a result of responses to the questionnaires; 56.3% (40/71) were deferred by the DHAQ, and an additional 43.7% (31/71) were deferred due to risks identified by the HQ but not by the DHAQ. Fourteen donors self-deferred; 11 indicated on the HQ that they should not donate blood on that day but did not use the confidential self-exclusion option on the DHAQ, and three used the self-exclusion option on the DHAQ but did not indicate that they should not donate blood on the HQ. The HQ identified a blood contact or risk factor for HIV/AIDS or sexually transmitted infection that was not identified by the DHAQ in 0.1% to 2.7% of donors. CONCLUSION: A self-administered computerized questionnaire may increase risk reporting by blood donors

Experience of sexual coercion and risky sexual behavior among Ugandan university students

<p>Abstract</p> <p>Background</p> <p>Growing worldwide evidence shows that the experience of sexual coercion is fairly prevalent among young people and is associated with risky sexual behavior thereafter. The causal mechanisms behind this are unclear but may be dependent on specific contextual determinants. Little is known about factors that could buffer the negative effects of coercion. The aim of this study was to assess the association between the experience of sexual coercion and risky sexual behavior among university students of both sexes in Uganda.</p> <p>Methods</p> <p>In 2005, 980 (80%) out of a total of 1,220 students enrolled in Mbarara University of Science and Technology in Uganda participated in a self-administered questionnaire covering socio-demographic and religious factors, social capital, mental health, alcohol use, and sexual behavior. A validated scale of six items was used to assess the experience of sexual coercion. Logistic regression analyses were applied to control for confounders. Potential buffering factors were analyzed by testing for effect modification.</p> <p>Results</p> <p>Fifty-nine percent of those who responded had previously had sexual intercourse. Among the male students 29.0%, and among the female students 33.1% reported having had some experience of sexual coercion. After controlling for age, gender, and educational level of household of origin, role of religion and trust in others sexual coercion was found to be statistically significantly associated with previously had sex (OR 1.6, 95% CI; 1.1-2.3), early sexual debut (OR 2.4, 95% CI; 1.5-3.7), as well as with having had a great number of sexual partners (OR 1.9, 95% CI; 1.2-3.0), but not with inconsistent condom use.</p> <p>Scoring low on an assessment of mental health problems, reporting high trust in others, or stating that religion played a major role in one's family of origin seemed to buffer the negative effect that the experience of sexual coercion had on the likelihood of having many sexual partners.</p> <p>Conclusion</p> <p>The findings of this study suggest that the experience of sexual coercion is common among youth/young adults in Uganda and is subsequently associated with risky sexual behavior in both sexes. The existence of individual and contextual factors that buffer the effects mentioned was also demonstrated. In the Ugandan context, this has implications for policy formulation and the implementation of preventive strategies for combating HIV/AIDS.</p

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Losing the Ability in Activities of Daily Living in the Oldest Old: A Hierarchic Disability Scale from the Newcastle 85+ Study

Objectives: To investigate the order in which 85 year olds develop difficulty in performing a wide range of daily activities covering basic personal care, household care and mobility. Design: Cross-sectional analysis of baseline data from a cohort study. Setting: Newcastle upon Tyne and North Tyneside, UK. Participants: Individuals born in 1921, registered with participating general practices. Measurements: Detailed health assessment including 17 activities of daily living related to basic personal care, household care and mobility. Questions were of the form ‘Can you … ’ rather than ‘Do you… ’ Principal Component Analysis (PCA) was used to confirm a single underlying dimension for the items and Mokken Scaling was used to determine a subsequent hierarchy. Validity of the hierarchical scale was assessed by its associations with known predictors of disability. Results: 839 people within the Newcastle 85+ study for whom complete information was available on self-reported Activities of Daily Living (ADL). PCA confirmed a single underlying dimension; Mokken scaling confirmed a hierarchic scale where ‘Cutting toenails ’ was the first item with which participants had difficulty and ‘feeding ’ the last. The ordering of loss differed between men and women. Difficulty with ‘shopping ’ and ‘heavy housework ’ were reported earlier by women whilst men reported ‘walking 400 yards ’ earlier. Items formed clusters corresponding to strength, balance, lower and upper bod

Sensitivity of Chaos Measures in Detecting Stress in the Focusing Control Mechanism of the Short-Sighted Eye

yesWhen fixating on a stationary object, the power of the eye’s lens fluctuates. Studies have suggested that changes in these so-called microfluctuations in accommodation may be a factor in the onset and progression of short-sightedness. Like many physiological signals, the fluctuations in the power of the lens exhibit chaotic behaviour. A breakdown or reduction in chaos in physiological systems indicates stress to the system or pathology. The purpose of this study was to determine whether the chaos in fluctuations of the power of the lens changes with refractive error, i.e. how short-sighted a subject is, and/or accommodative demand, i.e. the effective distance of the object that is being viewed. Six emmetropes (EMMs, non-short-sighted), six early-onset myopes (EOMs, onset of short-sightedness before the age of 15), and six late-onset myopes (LOMs, onset of short-sightedness after the age of 15) took part in the study. Accommodative microfluctuations were measured at 22 Hz using an SRW-5000 autorefractor at accommodative demands of 1 D (dioptres), 2 D, and 3 D. Chaos theory analysis was used to determine the embedding lag, embedding dimension, limit of predictability, and Lyapunov exponent. Topological transitivity was also tested for. For comparison, the power spectrum and standard deviation were calculated for each time record. The EMMs had a statistically significant higher Lyapunov exponent than the LOMs ( 0.64±0.330.64±0.33 vs. 0.39±0.20 D/s0.39±0.20 D/s ) and a lower embedding dimension than the LOMs ( 3.28±0.463.28±0.46 vs. 3.67±0.493.67±0.49 ). There was insufficient evidence (non-significant p value) of a difference between EOMs and EMMs or EOMs and LOMs. The majority of time records were topologically transitive. There was insufficient evidence of accommodative demand having an effect. Power spectrum analysis and assessment of the standard deviation of the fluctuations failed to discern differences based on refractive error. Chaos differences in accommodation microfluctuations indicate that the control system for LOMs is under stress in comparison to EMMs. Chaos theory analysis is a more sensitive marker of changes in accommodation microfluctuations than traditional analysis methods

Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report

<p>Abstract</p> <p>Background</p> <p>Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases.</p> <p>Case Presentation</p> <p>We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP) gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrP^res) in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI.</p> <p>Conclusions</p> <p>In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG), genetic analysis, and nuclear imaging may aid in diagnosis.</p

Practice nursing in Australia: A review of education and career pathways

<p>Abstract</p> <p>Background</p> <p>Nurses in Australia are often not educated in their pre registration years to meet the needs of primary care. Careers in primary care may not be as attractive to nursing graduates as high-tech settings such as intensive or acute care. Yet, it is in primary care that increasingly complex health problems are managed. The Australian government has invested in incentives for general practices to employ practice nurses. However, no policy framework has been developed for practice nursing to support career development and post-registration education and training programs are developed in an ad hoc manner and are not underpinned by core professional competencies. This paper reports on a systematic review undertaken to establish the available evidence on education models and career pathways with a view to enhancing recruitment and retention of practice nurses in primary care in Australia.</p> <p>Methods</p> <p>Search terms describing education models, career pathways and policy associated with primary care (practice) nursing were established. These search terms were used to search electronic databases. The search strategy identified 1394 citations of which 408 addressed one or more of the key search terms on policy, education and career pathways. Grey literature from the UK and New Zealand internet sites were sourced and examined. The UK and New Zealand Internet sites were selected because they have well established and advanced developments in education and career pathways for practice nurses.</p> <p>Two reviewers examined titles, abstracts and studies, based on inclusion and exclusion criteria. Disagreement between the reviewers was resolved by consensus or by a third reviewer.</p> <p>Results</p> <p>Significant advances have been made in New Zealand and the UK towards strengthening frameworks for primary care nursing education and career pathways. However, in Australia there is no policy at national level prepare nurses to work in primary care sector and no framework for education or career pathways for nurses working in that sector.</p> <p>Conclusion</p> <p>There is a need for national training standards and a process of accreditation for practice nursing in Australia to support the development of a responsive and sustainable nursing workforce in primary care and to provide quality education and career pathways.</p

Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)