Bayesian testing of many hypotheses ×\times many genes: A study of sleep apnea

Substantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (e.g., diseased vs. nondiseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes. However, many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS241 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Bayesian testing of many hypothesis x many genes: a study of sleep apnea

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSubstantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (eg. diseased vs. non-diseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes.However,many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans

Few-emitter lasing in single ultra-small nanocavities

Funding: We acknowledge support from EPSRC grants EP/G060649/1, EP/L027151/1, EP/G037221/1, EP/T014032/1, EPSRC NanoDTC, and from the European Research Council (ERC) under Horizon 2020 research and innovation programme PICOFORCE (Grant Agreement No. 883703), THOR (Grant Agreement No. 829067) and POSEIDON (Grant Agreement No. 861950). O.S.O acknowledges the support of a Rubicon fellowship from the Netherlands Organisation for Scientific Research.Lasers are ubiquitous for information storage, processing, communications, sensing, biological research, and medical applications. To decrease their energy and materials usage, a key quest is to miniaturize lasers down to nanocavities. Obtaining the smallest mode volumes demands plasmonic nanocavities, but for these, gain comes from only single or few emitters. Until now, lasing in such devices was unobtainable due to low gain and high cavity losses. Here, we demonstrate a form of “few emitter lasing” in a plasmonic nanocavity approaching the single-molecule emitter regime. The few-emitter lasing transition significantly broadens, and depends on the number of molecules and their individual locations. We show this non-standard few-emitter lasing can be understood by developing a theoretical approach extending previous weak-coupling theories. Our work paves the way for developing nanolaser applications as well as fundamental studies at the limit of few emitters.Publisher PDFPeer reviewe

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3-/- . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA

The role of obesity, different fat compartments and sleep apnea severity in circulating leptin levels: the Icelandic Sleep Apnea Cohort study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between obstructive sleep apnea (OSA) severity and leptin levels differs depending on obesity level.Cross-sectional study of 452 untreated OSA patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±s.d.), body mass index (BMI) 32.7±5.3 kg m(-2) and apnea-hypopnea index 40.2±16.1 events per h. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed, as well as fasting serum morning leptin levels were measured.Leptin levels were more highly correlated with BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI or =35 kg m(-2)). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.NIH/HL72067/HL94307, Eimskip Fund of the University of Iceland, Landspitali University Hospital Research Fun

The design of RIP belts impacts the reliability and quality of the measured respiratory signals.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPurpose: Evaluate the effect of respiratory inductance plethysmography (RIP) belt design on the reliability and quality of respiratory signals. A comparison of cannula flow to disposable cut-to-fit, semi-disposable folding and disposable RIP belts was performed in clinical home sleep apnea testing (HSAT) studies. Methods: This was a retrospective study using clinical HSAT studies. The signal reliability of cannula, thorax, and abdomen RIP belts was determined by automatically identifying periods during which the signals did not represent respiratory airflow and breathing movements. Results were verified by manual scoring. RIP flow quality was determined by examining the correlation between the RIP flow and cannula flow when both signals were considered reliable. Results: Of 767 clinical HSAT studies, mean signal reliability of the cut-to-fit, semi-disposable, and disposable thorax RIP belts was 83.0 ± 26.2%, 76.1 ± 24.4%, and 98.5 ± 9.3%, respectively. The signal reliability of the cannula was 92.5 ± 16.1%, 87.0 ± 23.3%, and 85.5 ± 24.5%, respectively. The automatic assessment of signal reliability for the RIP belts and cannula flow had a sensitivity of 50% and a specificity of 99% compared with manual assessment. The mean correlation of cannula flow to RIP flow from the cut-to-fit, semi-disposable, and disposable RIP belts was 0.79 ± 0.24, 0.52 ± 0.20, and 0.86 ± 0.18, respectively. Conclusion: The design of RIP belts affects the reliability and quality of respiratory signals. The disposable RIP belts that had integrated contacts and did not fold on top of themselves performed the best. The cut-to-fit RIP belts were most likely to be unreliable, and the semi-disposable folding belts produced the lowest-quality RIP flow signals compared to the cannula flow signal. Keywords: Obstructive sleep apnea (OSA); Respiratory airflow; Respiratory inductance plethysmography (RIP) belts; Signal quality; Signal reliability.Icelandic Research Fund Horizon 2020 grant (H2020-SMEINST-2-2016-2017

Single slice vs. volumetric MR assessment of visceral adipose tissue: reliability and validity among the overweight and obese.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Visceral adipose tissue (VAT) is associated with abnormal cardiovascular and metabolic profiles. Total VAT volume of the abdominal compartment by magnetic resonance imaging (MRI) is the gold-standard measurement for VAT but is costly and time consuming. Prior studies suggest VAT area on a single slice MR image may serve as a surrogate for total VAT volume but it is unknown if this relationship is maintained in overweight and obese men and women. Untreated sleep apnea subjects enrolled into the Icelandic Sleep Apnea Cohort (ISAC) underwent abdominal MRI. VAT area and subcutaneous adipose tissue (SAT) area at the L2-L3 and L4-L5 interspaces and total VAT and SAT volumes were determined by manual examination using image analysis software; 539 men and 129 women with mean ages of 54.1 and 58.8 years and mean BMI of 32.2 kg/m(2) and 33.7 kg/m(2), respectively, were studied. Mean total VAT volume was 40% smaller and mean total SAT was 25% larger among females compared with males. The correlation with VAT volume was significantly larger for L2-L3 VAT area (r = 0.96) compared to L4-L5 VAT area (r = 0.83). The difference in correlation coefficients was statistically significant (nonparametric bootstrap P < 0.001 with 95% confidence interval (CI) for the difference from 0.11 to 0.15. VAT area at L2-L3 was also significantly better correlated with VAT volume than traditional anthropometric variables. Linear regression analyses demonstrated that L2-L3 area alone was sufficient for predicting total VAT volume and that the nature of the linear association was maintained across all levels of obesity and in both genders.NIH HL070267 HL09430

Systematic literature review of determinants of sedentary behaviour in older adults:a DEDIPAC study

BACKGROUND: Older adults are the most sedentary segment of society and high sedentary time is associated with poor health and wellbeing outcomes in this population. Identifying determinants of sedentary behaviour is a necessary step to develop interventions to reduce sedentary time. METHODS: A systematic literature review was conducted to identify factors associated with sedentary behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between 2000 and May 2014. The search strategy was based on four key elements: (a) sedentary behaviour and its synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of determinants (e.g. environmental, behavioural). Articles were included in the review if specific information about sedentary behaviour in older adults was reported. Studies on samples identified by disease were excluded. Study quality was rated by means of QUALSYST. The full review protocol is available from PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio-ecological model framework. RESULTS: Twenty-two original studies were identified out of 4472 returned by the systematic search. These included 19 cross-sectional, 2 longitudinal and 1 qualitative studies, all published after 2011. Half of the studies were European. The study quality was generally high with a median of 82 % (IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently investigated with consistent positive association for age, negative for retirement, obesity and health status. Only four studies considered environmental determinants suggesting possible association with mode of transport, type of housing, cultural opportunities and neighbourhood safety and availability of places to rest. Only two studies investigated mediating factors. Very limited information was available on contexts and sub-domains of sedentary behaviours. CONCLUSION: Few studies have investigated determinants of sedentary behaviour in older adults and these have to date mostly focussed on personal factors, and qualitative studies were mostly lacking. More longitudinal studies are needed as well as inclusion of a broader range of personal and contextual potential determinants towards a systems-based approach, and future studies should be more informed by qualitative work

On the possibility of a terahertz light emitting diode based on a dressed quantum well

We consider theoretically the realization of a tunable terahertz light emitting diode from a quantum well with dressed electrons placed in a highly doped p-n junction. In the considered system the strong resonant dressing field forms dynamic Stark gaps in the valence and conduction bands and the electric field inside the p-n junction makes the QW asymmetric. It is shown that the electrons transiting through the light induced Stark gaps in the conduction band emit photons with energy directly proportional to the dressing field. This scheme is tunable, compact, and shows a fair efficiency.Comment: 6 pages, 5 figure