Uncertainty in Crowd Data Sourcing under Structural Constraints

Applications extracting data from crowdsourcing platforms must deal with the uncertainty of crowd answers in two different ways: first, by deriving estimates of the correct value from the answers; second, by choosing crowd questions whose answers are expected to minimize this uncertainty relative to the overall data collection goal. Such problems are already challenging when we assume that questions are unrelated and answers are independent, but they are even more complicated when we assume that the unknown values follow hard structural constraints (such as monotonicity). In this vision paper, we examine how to formally address this issue with an approach inspired by [Amsterdamer et al., 2013]. We describe a generalized setting where we model constraints as linear inequalities, and use them to guide the choice of crowd questions and the processing of answers. We present the main challenges arising in this setting, and propose directions to solve them.Comment: 8 pages, vision paper. To appear at UnCrowd 201

Comparative lipid profiling dataset of the inflammation-induced optic nerve regeneration.

In adult mammals, retinal ganglion cells (RGCs) fail to regenerate following damage. As a result, RGCs die after acute injury and in progressive degenerative diseases such as glaucoma; this can lead to permanent vision loss and, eventually, blindness. Lipids are crucial for the development and maintenance of cell membranes, myelin sheaths, and cellular signaling pathways, however, little is known about their role in axon injury and repair. Studies examining changes to the lipidome during optic nerve (ON) regeneration could greatly inform treatment strategies, yet these are largely lacking. Experimental animal models of ON regeneration have facilitated the exploration of the molecular determinants that affect RGC axon regeneration. Here, we analyzed lipid profiles of the ON and retina in an ON crush rat model using liquid chromatography-mass spectrometry. Furthermore, we investigated lipidome changes after ON crush followed by intravitreal treatment with Zymosan, a yeast cell wall derivative known to enhance RGC regeneration. This data is available at the NIH Common Fund's Metabolomics Data Repository and Coordinating Center (supported by NIH grant, U01-DK097430) website, the Metabolomics Workbench, http://www.metabolomicsworkbench.org, where it has been assigned Project ID: PR000661. The data can be accessed directly via it's Project DOI: doi: 10.21,228/M87D53

Unusual Metabolism and Hypervariation in the Genome of a Gracilibacterium (BD1-5) from an Oil-Degrading Community.

The candidate phyla radiation (CPR) comprises a large monophyletic group of bacterial lineages known almost exclusively based on genomes obtained using cultivation-independent methods. Within the CPR, Gracilibacteria (BD1-5) are particularly poorly understood due to undersampling and the inherent fragmented nature of available genomes. Here, we report the first closed, curated genome of a gracilibacterium from an enrichment experiment inoculated from the Gulf of Mexico and designed to investigate hydrocarbon degradation. The gracilibacterium rose in abundance after the community switched to dominance by Colwellia Notably, we predict that this gracilibacterium completely lacks glycolysis, the pentose phosphate and Entner-Doudoroff pathways. It appears to acquire pyruvate, acetyl coenzyme A (acetyl-CoA), and oxaloacetate via degradation of externally derived citrate, malate, and amino acids and may use compound interconversion and oxidoreductases to generate and recycle reductive power. The initial genome assembly was fragmented in an unusual gene that is hypervariable within a repeat region. Such extreme local variation is rare but characteristic of genes that confer traits under pressure to diversify within a population. Notably, the four major repeated 9-mer nucleotide sequences all generate a proline-threonine-aspartic acid (PTD) repeat. The genome of an abundant Colwellia psychrerythraea population has a large extracellular protein that also contains the repeated PTD motif. Although we do not know the host for the BD1-5 cell, the high relative abundance of the C. psychrerythraea population and the shared surface protein repeat may indicate an association between these bacteria.IMPORTANCE CPR bacteria are generally predicted to be symbionts due to their extensive biosynthetic deficits. Although monophyletic, they are not monolithic in terms of their lifestyles. The organism described here appears to have evolved an unusual metabolic platform not reliant on glucose or pentose sugars. Its biology appears to be centered around bacterial host-derived compounds and/or cell detritus. Amino acids likely provide building blocks for nucleic acids, peptidoglycan, and protein synthesis. We resolved an unusual repeat region that would be invisible without genome curation. The nucleotide sequence is apparently under strong diversifying selection, but the amino acid sequence is under stabilizing selection. The amino acid repeat also occurs in a surface protein of a coexisting bacterium, suggesting colocation and possibly interdependence

miRNA-140-5p: new avenue for pulmonary arterial hypertension drug development?

Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Pathologically, PAH is characterised by sustained vasoconstriction and progressive obliteration of small pulmonary arteries through a process of medial thickening, intimal fibrosis and the formation of angioproliferative lesions. Current treatments target the sustained vasoconstriction via either the prostacyclin, endothelin or nitric oxide pathway but do little to address the underlying progressive proliferative vascular disease. Dysregulated expression of microRNA (miR) has been identified in PAH and we have recently highlighted reduced miR-140-5p in patients with PAH. Replacement of miR-140-5p attenuated disease in animal models with the regulation of Smurf1, a E3 ubiquitin ligase targeting BMPR2 as one identified mechanism. These data highlight Smurf1 inhibition as a treatment for PAH

A Coboundary Morphism For The Grothendieck Spectral Sequence

Given an abelian category $\mathcal{A}$ with enough injectives we show that a short exact sequence of chain complexes of objects in $\mathcal{A}$ gives rise to a short exact sequence of Cartan-Eilenberg resolutions. Using this we construct coboundary morphisms between Grothendieck spectral sequences associated to objects in a short exact sequence. We show that the coboundary preserves the filtrations associated with the spectral sequences and give an application of these result to filtrations in sheaf cohomology.Comment: 18 page

A standardised sampling protocol for robust assessment of reach-scale fish community diversity in wadeable New Zealand streams

The New Zealand fish fauna contains species that are affected not only by river system connectivity, but also by catchment and local-scale changes in landcover, water quality and habitat quality. Consequently, native fish have potential as multi-scale bioindicators of human pressure on stream ecosystems, yet no standardised, repeatable and scientifically defensible methods currently exist for effectively quantifying their abundance or diversity in New Zealand stream reaches. Here we report on the testing of a back-pack electrofishing method, modified from that used by the United States Environmental Protection Agency, on a wide variety of wadeable stream reaches throughout New Zealand. Seventy-three first- to third-order stream reaches were fished with a single pass over 150-345 m length. Time taken to sample a reach using single-pass electrofishing ranged from 1-8 h. Species accumulation curves indicated that, irrespective of location, continuous sampling of 150 stream metres is required to accurately describe reach-scale fish species richness using this approach. Additional species detection beyond 150 m was rare (<10%) with a single additional species detected at only two out of the 17 reaches sampled beyond this distance. A positive relationship was also evident between species detection and area fished, although stream length rather than area appeared to be the better predictor. The method tested provides a standardised and repeatable approach for regional and/or national reporting on the state of New Zealand's freshwater fish communities and trends in richness and abundance over time

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Baseline predictors of remission, pain and fatigue in rheumatoid arthritis: the TITRATE trial.

BACKGROUND: Clinical trials show intensive treatment to induce remission is effective in patients with highly active rheumatoid arthritis (RA). The TITRATE trial showed that the benefits of intensive treatment also extend to moderately active RA. However, many patients failed to achieve remission or show improvements in pain and fatigue. We investigated whether baseline predictors could identify treatment non-responders. METHODS: The impact of obesity, depression, anxiety and illness perception on RA outcomes, including disease activity, remission, pain and fatigue were determined using a pre-planned secondary analysis of the TITRATE trial data. RESULTS: Body mass index was associated with disease activity levels and remission: obese patients had a higher overall disease activity and fewer obese patients achieved remission. Intensive management was not associated with increased remission in these patients. Obesity was also associated with increased overall pain and fatigue. Anxiety, depression and health perceptions had no discernible impact on disease activity but were associated with high levels of pain and fatigue. There was a strong association between anxiety and high pain scores; and between depression and high fatigue scores; and health perception was strongly related to both. None of the predictors had an important impact on pain and fatigue reduction in cross-sectional analysis. CONCLUSIONS: Disease activity is higher in obese patients and they have fewer remissions over 12 months. Anxiety, depression and health perceptions were associated with higher pain and fatigue scores. Intensive management strategies need to account for these baseline features as they impact significantly on clinical and psychological outcomes. TRIAL REGISTRATION: ISRCTN 70160382 ; date registered 16 January 2014

Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe