Development of the Rural Active Living Perceived Environmental Support Scale (RALPESS)

Background: Evidence supports the role of physical and social environments in active living, including perception of environment. However, measurement of perceived environments in rural settings is lacking. This study describes the development of the Rural Active Living Perceived Environmental Support Scale (RALPESS). Methods: Premised on social ecological and cognitive perspectives, 85 initial items were generated through a literature review and a mixed-methods investigation of activity-friendly environments. Items were organized by resource areas town center, indoor and outdoor physical activity areas, schools, churches, and areas around the home/neighborhood-and submitted for expert panel review. In 2009, a revised questionnaire was disseminated to adolescents, parents, public school staff, and older adults in 2 rural southeastern United States counties. Principal component analysis with varimax rotation was used to explore factor structure (n = 542). Results: The final analysis yielded 33 items with 7 factors: 1) church facilities, 2) town center connectivity, 3) indoor areas, 4) around the home/neighborhood, 5) town center physical activity resources, 6) school grounds, and 7) outdoor areas. Conclusions: The RALPESS is a valid, internally consistent, and practically useful instrument to measure perceptions of rural environments in the context of physical activity across the lifespan. Confirmatory factor analysis is recommended to validate factor structure

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology

Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing. Definitions consistent with a patient-centered approach emphasize and recognize that a clinical test result\u27s utility depends on the context in which it is used and are particularly relevant to molecular diagnostic testing because of the nature of the information they provide. Debates surrounding levels and types of evidence needed to properly evaluate the clinical value of molecular diagnostics are increasingly important because the growing body of knowledge, stemming from the increase of genomic medicine, provides many new opportunities for molecular testing to improve health care. We address the challenges in defining the clinical utility of molecular diagnostics for inherited diseases or cancer and provide assessment recommendations. Starting with a modified analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications model for addressing clinical utility of molecular diagnostics with a variety of testing purposes, we recommend promotion of patient-centered definitions of clinical utility that appropriately recognize the valuable contribution of molecular diagnostic testing to improve patient care

Next-generation carrier screening

Purpose: Carrier screening for recessive Mendelian disorders traditionally employs focused genotyping to interrogate limited sets of mutations most prevalent in specific ethnic groups. We sought to develop a next-generation DNA sequencing–based workflow to enable analysis of a more comprehensive set of disease-causing mutations. Methods: We utilized molecular inversion probes to capture the protein-coding regions of 15 genes from genomic DNA isolated from whole blood and sequenced those regions using the Illumina HiSeq 2000 (Illumina, San Diego, CA). To assess the quality of the resulting data, we measured both the fraction of the targeted region yielding high-quality genotype calls, and the sensitivity and specificity of those calls by comparison with conventional Sanger sequencing across hundreds of samples. Finally, to improve the overall accuracy for detecting insertions and deletions, we introduce a novel assembly-based approach that substantially increases sensitivity without reducing specificity. Results: We generated high-quality sequence for at least 99.8% of targeted base pairs in samples derived from blood and achieved high concordance with Sanger sequencing (sensitivity >99.9%, specificity >99.999%). Our novel algorithm is capable of detecting insertions and deletions inaccessible by current methods. Conclusion: Our next-generation DNA sequencing–based approach yields the accuracy and completeness necessary for a carrier screening test

Terrestrial emigration behaviour of two invasive crayfish species

To disperse between isolated waterbodies, freshwater organisms must often cross terrestrial barriers and many freshwater animals that are incapable of flight must rely on transport via flooding events, other animals or anthropogenic activity. Decapods such as crayfish, on the other hand, can disperse to nearby waterbodies by walking on land, a behaviour that has facilitated the spread of invasive species. Overland movement could play a key role in the management of non-native crayfish, though to what extent terrestrial emigration occurs in different species is poorly understood. Here, we directly compared the terrestrial emigration tendency of two non-native crayfish species in Great Britain; red swamp (Procambarus clarkii) and signal (Pacifastacus leniusculus) crayfish. We found that both species emigrated from the water and that there was no significant difference in terms of their terrestrial emigration tendency, suggesting that there is a risk both of these species will migrate overland and disperse to new habitats. This study shows that terrestrial emigration is an important behavioural trait to consider when preventing the escape of crayfish from aquaculture and further spread of invasive species

Expansion of the Genomic Encyclopedia of Bacteria and Archaea

To date the vast majority of bacterial and archaeal genomes sequenced are of rather limited phylogenetic diversity as they were chosen based on their physiology and/ or medical importance. The Genomic Encyclopedia of Bacteria and Archaea (GEBA) project (Wu et al. 2009) is aimed at systematically filling the gaps of the tree of life with phylogenetically diverse reference genomes. However more than 99 percent of microorganisms elude current culturing attempts, severely limiting the ability to recover complete or even partial genomes of these largely mysterious species. These limitations gave rise to the GEBA uncultured project. Here we propose to use single cell genomics to massively expand the Genomic Encyclopedia of Bacteria and Archaea by targeting 80 single cell representatives of uncultured candidate phyla which have no or very few cultured representatives. Generating these reference genomes of uncultured microbes will dramatically increase the discovery rate of novel protein families and biological functions, shed light on the numerous underrepresented phyla that likely play important roles in the environment, and will assist in improving the reconstruction of the evolutionary history of Bacteria and Archaea. Moreover, these data will improve our ability to interpret metagenomics sequence data from diverse environments, which will be of tremendous value for microbial ecology and evolutionary studies to come

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Breastfeeding Experiences of Women Who have Survived Intimate Partner Violence

Breastfeeding has multiple benefits for women who have survived intimate partner violence (IPV), but little is known about the experiences of women in this population and the impact that IPV has on the breastfeeding journey. This pilot study aimed to explore the lived experiences of breastfeeding mothers who have survived IPV. Two women who had survived IPV and were breastfeeding participated in an online semi-structured interview, which invited them to share their expectations of breastfeeding, their birth experiences, positive and challenging breastfeeding experiences, the kinds of support they received, and advice they wanted to share with health professionals and other women. An interpretative phenomenological analysis identified three themes from the interviews: identity and sense of self; isolation; and the impact of support. Despite being a challenging process, breastfeeding was an empowering experience that facilitated a sense of purpose and identity, something IPV had deconstructed