A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD

Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL-PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL-PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL-PCD has been translated into other languages and is awaiting psychometric testing

Tai Chi for Osteopenic Women: Design and Rationale of a Pragmatic Randomized Controlled Trial

Background: Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks. Methods/Design: A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk. Discussion: Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study. Trial registration: This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012

Monitoring of Collapsed Built-Up Areas with High Resolution SAR Images

A 16-year-old male with cystic fibrosis (CF) was admitted to hospital with a severe infective exacerbation. Despite standard management, including conventionally selected intravenous antibiotics for Pseudomonas aeruginosa chest physiotherapy, and institution of noninvasive ventilation (NIV) for progressive hypercapneic respiratory failure, he continued to deteriorate. Direct sputum sensitivity testing (DSST) revealed a novel combination of antibiotics that resulted in a rapid and remarkable clinical improvement. DSST is a form of "whole" sputum sensitivity testing that provides information on antibiotic synergy, and may more accurately reflect in vivo antibiotic sensitivity patterns in cystic fibrosis.</p

Penerapan Metode Scoring System untuk Penilaian Latihan Pemahaman Materi Ibadah Sholat Fardhu dan Sunnah

Ibadah Sholat merupakan kewajiban yang harus senantiasa dikerjakan oleh umat muslim. Tidak hanya mengutamakan ibadah sholat fardhu, melainkan Allah juga menganjurkan untuk menyempurnakan dengan melakukan ibadah sholat sunnah. Dalam pelaksanaannya, umat muslim masih membutuhkan panduan mengenai tuntunan sholat tersebut secara praktis dan bersifat mobile, sementara mobilitas manusia semakin tinggi. Oleh karena itu, pada penelitian ini telah membangun aplikasi tuntunan sholat baik fardhu dan sunnah berbasis android yang dilengkapi dengan latihan kemampuan pemahaman materi mengenai sholat fardhu dan sunnah. Tujuannya adalah mampu meningkatkan kualitas setiap orang yang ingin belajar sholat dengan melakukan latihan kemampuan pemahaman materi tersebut. Sistem penilaiannya menggunakan metode pengukuran, yaitu metode scoring system. Metode scoring system adalah metode yang memberikan evaluasi terhadap kelayakan subyek tes dalam bentuk nilai. Dari hasil pengujian menunjukkan bahwasannya aplikasi penilaian latihan ini mampu menilai tingkat pemahaman materi berdasarkan hasil tes yang diperoleh menggunakan metode scoring system

Kori Bustards (\u3ci\u3eArdeotis kori\u3c/i\u3e) respond to vegetation density and elevation in the Northern Tuli Game Reserve, Botswana L\u27abondance de l\u27Outarde kori (\u3ci\u3eArdeotis kori\u3c/i\u3e) varie selon la végétation et l\u27élévation dans la réserve de chasse de Northern Tuli, Botswana

Conservation planning and decision making for species of concern requires precise information on abundance and habitat associations. We conducted transect surveys throughout the Northern Tuli Game Reserve, Botswana during June–July 2014 and May– July 2015 to estimate the occupancy and abundance of Kori Bustards (Ardeotis kori). The probability of occupancy of Kori Bustards was greater in areas with tree canopy cover ≤ 50% (ψ2014 = 0.37, SE ± 0.09; ψ2015 = 0.39, SE ± 0.06) when compared with areas with tree canopy cover \u3e 50% (ψ2014 = 0.00, SE ± 0.00; ψ2015 = 0.00, SE ± 0.00). Densities of Kori Bustards ranged from 0.03–5.02 individuals/km² at our study sites. They showed annual variation, and densities were highest in areas where vegetation was classified as sparse or bare soil. Areas at low (≤ 540 m above sea level) and high (≥ 540 m above sea level) elevations at our study sites also exhibited differences in density of Kori Bustards but elevational differences varied among years. Areas categorized as both sparse vegetation and higher elevation had the highest estimated densities in 2014 with 5.02 individuals/km². Areas categorized as sparse vegetation and lower elevation had the highest densities in 2015 with 2.20 individuals/km². Our study demonstrates that areas of sparse vegetation and open canopy areas are important to Kori Bustards. However, open canopy areas outside of reserves may be at risk of conversion to row crop and other forms of agriculture as human populations and demands for food increase. Habitat-specific information will be useful for future studies to identify risks during landscape conservation planning within the range of the Kori Bustard. La planification de la conservation et la prise de décisions pour les espèces préoccupantes requièrent des données précises sur leur abondance et leurs associations avec l\u27habitat. Nous avons effectué des relevés par transects dans la réserve de chasse de Northern Tuli, au Botswana, en juin-juillet 2014 et mai-juillet 2015, afin de déterminer l\u27occurrence et la densité d\u27Outardes kori (Ardeotis kori). La probabilité d\u27occurrence des outardes était supérieure dans les endroits où la voûte forestière couvrait ≤ 50 % (ψ2014 = 0,37, écarttype ± 0,09; ψ2015 = 0,39, écart-type ± 0,06) comparativement aux endroits où la voûte couvrait \u3e 50 % (ψ2014 = 0,00, écart-type ± 0,00; ψ2015 = 0,00, écart-type ± 0,00). Les densités de cette outarde s\u27élevaient de 0,03 à 5,02 individus/km² dans nos sites d\u27étude. Les densités montraient des variations annuelles et étaient plus élevées dans les endroits où la végétation était classée comme « éparse » ou « sol nu ». Les densités ont aussi différé selon les endroits de basse (≤ 540 m au-dessus du niveau de la mer) ou de haute (≥ 540 m ASL) élévation dans nos sites d\u27étude, et ces différences ont varié entre les années. Les endroits classés à la fois comme de végétation éparse et de haute élévation ont hébergé les densités les plus élevées en 2014, soit 5,02 individus/km². Les endroits classés à la fois comme de végétation éparse et de basse élévation ont hébergé les densités les plus élevées en 2015, soit 2,20 individus/km². Notre étude indique que les endroits de végétation éparse et ceux où la voûte est ouverte sont importants pour les Outardes kori. Toutefois, les endroits où la voûte forestière est ouverte à l\u27extérieur des réserves risquent peut-être d\u27être affectés à la culture en rangs ou à d\u27autres formes d\u27agriculture considérant que la population humaine et la demande alimentaire augmentent. Les données relatives à l\u27habitat seront utiles pour les éventuelles recherches visant à identifier les risques au moment de la planification de la conservation du paysage dans l\u27aire de répartition de l\u27Outarde kori

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Republished: Respiratory microbiota:Addressing clinical questions, informing clinical practice

Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted. We examine how an understanding of the respiratory microbiota both challenges fundamental assumptions and provides novel clinical insights into lung disease, and we set out a number of important targets for ongoing research.</p