Mixing Matrix Estimation From Sparse Mixtures With Unknown Number of Sources

In blind source separation, many methods have been proposed to estimate the mixing matrix by exploiting sparsity. However, they often need to know the source number a priori, which is very inconvenient in practice. In this paper, a new method, namely nonlinear projection and column masking (NPCM), is proposed to estimate the mixing matrix. A major advantage of NPCM is that it does not need any knowledge of the source number. In NPCM, the objective function is based on a nonlinear projection and its maxima just correspond to the columns of the mixing matrix. Thus a column can be estimated first by locating a maximum and then deflated by a masking operation. This procedure is repeated until the evaluation of the objective function decreases to zero dramatically. Thus the mixing matrix and the number of sources are estimated simultaneously. Because the masking procedure may result in some small and useless local maxima, particle swarm optimization (PSO) is introduced to optimize the objective function. Feasibility and efficiency of PSO are also discussed. Comparative experimental results show the efficiency of NPCM, especially in the cases where the number of sources is unknown and the sources are relatively less sparse.

Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression

Background: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.

Methods/Design: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression.

Study eligibility criteria: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias.

Data sources: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.  The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results.

Discussion: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.

Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation

Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA). To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA. The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria. Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review. Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.

Predicting avian distributions to evaluate spatiotemporal overlap with locust control operations in eastern Australia.

Locusts and grasshoppers cause considerable economic damage to agriculture worldwide. The Australian Plague Locust Commission uses multiple pesticides to control locusts in eastern Australia. Avian exposure to agricultural pesticides is of conservation concern, especially in the case of rare and threatened species. The aim of this study was to evaluate the probability of pesticide exposure of native avian species during operational locust control based on knowledge of species occurrence in areas and times of application. Using presence-absence data provided by the Birds Australia Atlas for 1998 to 2002, we developed a series of generalized linear models to predict avian occurrences on a monthly basis in 0.5 degrees grid cells for 280 species over 2 million km2 in eastern Australia. We constructed species-specific models relating occupancy patterns to survey date and location, rainfall, and derived habitat preference. Model complexity depended on the number of observations available. Model output was the probability of occurrence for each species at times and locations of past locust control operations within the 5-year study period. Given the high spatiotemporal variability of locust control events, the variability in predicted bird species presence was high, with 108 of the total 280 species being included at least once in the top 20 predicted species for individual space-time events. The models were evaluated using field surveys collected between 2000 and 2005, at sites with and without locust outbreaks. Model strength varied among species. Some species were under- or over-predicted as times and locations of interest typically did not correspond to those in the prediction data set and certain species were likely attracted to locusts as a food source. Field surveys demonstrated the utility of the spatially explicit species lists derived from the models but also identified the presence of a number of previously unanticipated species. These results also emphasize the need for special consideration of rare and threatened species that are poorly predicted by presence-absence models. This modeling exercise was a useful a priori approach in species risk assessments to identify species present at times and locations of locust control applications, and to discover gaps in our knowledge and need for further focused data collection.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.Molecular Psychiatry advance online publication, 15 April 2014; doi:10.1038/mp.2014.33.

A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma

Purpose: 

An ecology of religiosity: re-emphasizing relationships between humans and nonhumans

A growing anthropological literature on how various groups of people relate with nonhuman Others has questioned the universality of the conceptual binary between Nature and Culture and, particularly, the usefulness of the concept of 'Nature' to an understanding of human - nonhuman relationships. In light of this, what then becomes of ecology? In particular, can we retain the crucial ecological notions of system and form while bypassing 'Nature'? Drawing on Gregory Bateson's ecology of mind, I suggest that this is possible as long as we focus on processes and relationships. Moreover, the kinds of processes and relationships that more clearly highlight this endeavor are those that are informed by religious thoughts and actions. I offer the term 'an ecology of religiosity' to outline how an overall focus on relationships may dissolve a priori distinctions between Nature and Culture while foregrounding the context in which relationships reshape themselves through religious forms.

Communication of scientific uncertainty : international case studies on the development of folate and vitamin D Dietary Reference Values.

Transparent evidence-based decision making has been promoted worldwide to engender trust in science and policy making. Yet, little attention has been given to transparency implementation. The degree of transparency (focused on how uncertain evidence was handled) during the development of folate and vitamin D Dietary Reference Values was explored in three a priori defined areas: (i) value request; (ii) evidence evaluation; and (iii) final values.

Hydrologic landscape regionalisation using deductive classification and random forests

Landscape classification and hydrological regionalisation studies are being increasingly used in ecohydrology to aid in the management and research of aquatic resources. We present a methodology for classifying hydrologic landscapes based on spatial environmental variables by employing non-parametric statistics and hybrid image classification. Our approach differed from previous classifications which have required the use of an a priori spatial unit (e.g. a catchment) which necessarily results in the loss of variability that is known to exist within those units. The use of a simple statistical approach to identify an appropriate number of classes eliminated the need for large amounts of post-hoc testing with different number of groups, or the selection and justification of an arbitrary number. Using statistical clustering, we identified 23 distinct groups within our training dataset. The use of a hybrid classification employing random forests extended this statistical clustering to an area of approximately 228,000 km2 of south-eastern Australia without the need to rely on catchments, landscape units or stream sections. This extension resulted in a highly accurate regionalisation at both 30-m and 2.5-km resolution, and a less-accurate 10-km classification that would be more appropriate for use at a continental scale. A smaller case study, of an area covering 27,000 km2, demonstrated that the method preserved the intra- and inter-catchment variability that is known to exist in local hydrology, based on previous research. Preliminary analysis linking the regionalisation to streamflow indices is promising suggesting that the method could be used to predict streamflow behaviour in ungauged catchments. Our work therefore simplifies current classification frameworks that are becoming more popular in ecohydrology, while better retaining small-scale variability in hydrology, thus enabling future attempts to explain and visualise broad-scale hydrologic trends at the scale of catchments and continents.

Determining trends and environmental drivers from long-term marine mammal and seabird data : examples from Southern Australia

Climate change is acknowledged as an emerging threat for top-order marine predators, yet obtaining evidence of impacts is often difficult. In south-eastern Australia, a marine global warming hotspot, evidence suggests that climate change will profoundly affect pinnipeds and seabirds. Long-term data series are available to assess some species' responses to climate. Researchers have measured a variety of chronological and population variables, such as laying dates, chick or pup production, colony-specific abundance and breeding success. Here, we consider the challenges in accurately assessing trends in marine predator data, using long-term data series that were originally collected for other purposes, and how these may be driven by environmental change and variability. In the past, many studies of temporal changes and environmental drivers used linear analyses and we demonstrate the (theoretical) relationship between the magnitude of a trend, its variability, and the duration of a data series required to detect a linear trend. However, species may respond to environmental change in a nonlinear manner and, based on analysis of time-series from south-eastern Australia, it appears that the assumptions of a linear model are often violated, particularly for measures of population size. The commonly measured demographic variables exhibit different degrees of variation, which influences the ability to detect climate signals. Due to their generally lower year-to-year variability, we illustrate that monitoring of variables such as mass and breeding chronology should allow detection of temporal trends earlier in a monitoring programme than observations of breeding success and population size. Thus, establishing temporal changes with respect to climate change from a monitoring programme over a relatively short time period requires careful a priori choice of biological variables. © 2014 Springer-Verlag Berlin Heidelberg.

Modelling multilevel data in multimedia : A hierarchical factor analysis approach

Multimedia content understanding research requires rigorous approach to deal with the complexity of the data. At the crux of this problem is the method to deal with multilevel data whose structure exists at multiple scales and across data sources. A common example is modeling tags jointly with images to improve retrieval, classification and tag recommendation. Associated contextual observation, such as metadata, is rich that can be exploited for content analysis. A major challenge is the need for a principal approach to systematically incorporate associated media with the primary data source of interest. Taking a factor modeling approach, we propose a framework that can discover low-dimensional structures for a primary data source together with other associated information. We cast this task as a subspace learning problem under the framework of Bayesian nonparametrics and thus the subspace dimensionality and the number of clusters are automatically learnt from data instead of setting these parameters a priori. Using Beta processes as the building block, we construct random measures in a hierarchical structure to generate multiple data sources and capture their shared statistical at the same time. The model parameters are inferred efficiently using a novel combination of Gibbs and slice sampling. We demonstrate the applicability of the proposed model in three applications: image retrieval, automatic tag recommendation and image classification. Experiments using two real-world datasets show that our approach outperforms various state-of-the-art related methods.

Power, effects, confidence, and significance: an investigation of statistical practices in nursing research

Objectives: To (a) assess the statistical power of nursing research to detect small, medium, and large effect sizes; (b) estimate the experiment-wise Type I error rate in these studies; and (c) assess the extent to which (i) a priori power analyses, (ii) effect sizes (and interpretations thereof), and (iii) confidence intervals were reported. Design: Statistical review. Data sources: Papers published in the 2011 volumes of the 10 highest ranked nursing journals, based on their 5-year impact factors. Review methods: Papers were assessed for statistical power, control of experiment-wise Type I error, reporting of a priori power analyses, reporting and interpretation of effect sizes, and reporting of confidence intervals. The analyses were based on 333 papers, from which 10,337 inferential statistics were identified. Results: The median power to detect small, medium, and large effect sizes was .40 (interquartile range [. IQR]. = .24-.71), .98 (IQR= .85-1.00), and 1.00 (IQR= 1.00-1.00), respectively. The median experiment-wise Type I error rate was .54 (IQR= .26-.80). A priori power analyses were reported in 28% of papers. Effect sizes were routinely reported for Spearman's rank correlations (100% of papers in which this test was used), Poisson regressions (100%), odds ratios (100%), Kendall's tau correlations (100%), Pearson's correlations (99%), logistic regressions (98%), structural equation modelling/confirmatory factor analyses/path analyses (97%), and linear regressions (83%), but were reported less often for two-proportion z tests (50%), analyses of variance/analyses of covariance/multivariate analyses of variance (18%), t tests (8%), Wilcoxon's tests (8%), Chi-squared tests (8%), and Fisher's exact tests (7%), and not reported for sign tests, Friedman's tests, McNemar's tests, multi-level models, and Kruskal-Wallis tests. Effect sizes were infrequently interpreted. Confidence intervals were reported in 28% of papers. Conclusion: The use, reporting, and interpretation of inferential statistics in nursing research need substantial improvement. Most importantly, researchers should abandon the misleading practice of interpreting the results from inferential tests based solely on whether they are statistically significant (or not) and, instead, focus on reporting and interpreting effect sizes, confidence intervals, and significance levels. Nursing researchers also need to conduct and report a priori power analyses, and to address the issue of Type I experiment-wise error inflation in their studies. © 2013 .

Barriers to primary care clinician adherence to clinical guidelines for the management of low back pain: protocol of a systematic review and meta-synthesis of qualitative studies.

INTRODUCTION: Low back pain is the highest ranked condition contributing to years lived with disability, and is a significant economic and societal burden. Evidence-based clinical practice guidelines are designed to improve quality of care and reduce practice variation by providing graded recommendations based on the best available evidence. Studies of low back pain guideline implementation have shown no or modest effects at changing clinical practice. OBJECTIVES: To identify enablers and barriers to adherence to clinical practice guidelines for the management of low back pain. METHODS AND ANALYSIS: A systematic review and meta-synthesis of qualitative studies that will be conducted and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement guidelines. Eight databases will be searched using a priori inclusion/exclusion criteria. Two independent reviewers will conduct a structured review and meta-synthesis, and a third reviewer will arbitrate where there is disagreement. This protocol has been registered on PROSPERO 2014. ETHICS AND DISSEMINATION: Ethical approval is not required. The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically, in print and at conferences. Updates of the review will be conducted to inform and guide healthcare translation into practice. TRIAL REGISTRATION NUMBER: PROSPERO 2014:CRD42014012961. Available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014012961.

Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.

Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: a post hoc analysis

OBJECTIVE: Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression. METHODS: This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20. RESULTS: Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated. CONCLUSIONS: These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.