Get Another Worker? Active Crowdlearning With Sequential Arrivals

Engineering and Applied Science

Towards Better Definitions and Measures of Internet Security

Engineering and Applied Science

Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND: Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited. AIM: To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis. METHODS: A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution of symptoms back to baseline at the time of next clinic review. RESULTS: Thirty-nine patients were prescribed acetarsol suppositories between March 2008 and July 2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one with indeterminate colitis). Thirty-eight were included for analysis. The standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks. Clinical response was observed in 26 patients (68%). Of the 11 patients who had endoscopic assessment before and after treatment, nine (82%) showed endoscopic improvement and five (45%) were in complete remission (Wilcoxon signed-rank test p = 0.006). One patient developed a macular skin rash 1 week after commencing acetarsol, which resolved within 4 weeks of drug cessation. CONCLUSION: Acetarsol was effective for two out of every three patients with refractory proctitis. This cohort had failed a broad range of topical and systemic treatments, including anti-TNFα therapy. Clinical efficacy was reflected in significant endoscopic improvement. Adverse effects of acetarsol were rare

Contrastive Learning Using Spectral Methods

In many natural settings, the analysis goal is not to characterize a single data set in isolation, but rather to understand the difference between one set of observations and another. For example, given a background corpus of news articles together with writings of a particular author, one may want a topic model that explains word patterns and themes specific to the author. Another example comes from genomics, in which biological signals may be collected from different regions of a genome, and one wants a model that captures the differential statistics observed in these regions. This paper formalizes this notion of contrastive learning for mixture models, and develops spectral algorithms for inferring mixture components specific to a foreground data set when contrasted with a background data set. The method builds on recent moment-based estimators and tensor decompositions for latent variable models, and has the intuitive feature of using background data statistics to appropriately modify moments estimated from foreground data. A key advantage of the method is that the background data need only be coarsely modeled, which is important when the background is too complex, noisy, or not of interest. The method is demonstrated on applications in contrastive topic modeling and genomic sequence analysis.Engineering and Applied Science

Plasma contactor technology for Space Station Freedom

Hollow cathode plasma contactors were baselined for Space Station Freedom (SSF) to control the electrical potentials of surfaces to eliminate/mitigate damaging interactions with the space environment. The system represents a dual-use technology which is a direct outgrowth of the NASA electric propulsion program and in particular the technology development effort on ion thruster systems. Specific efforts include optimizing the design and configuration of the contactor, validating its required lifetime, and characterizing the contactor plume and electromagnetic interference. The plasma contact or subsystems include the plasma contact or unit, a power electronics unit, and an expellant management unit. Under this program these will all be brought to breadboard and engineering model development status. New test facilities were developed, and existing facilities were augmented, to support characterizations and life testing of contactor components and systems. The magnitude, scope, and status of the plasma contactor hardware development program now underway and preliminary test results on system components are discussed

Behind the Signs - a global review of fish sustainability information schemes

This paper presents the results of a global review of organisations that provide sustainable fisheries information — including ecolabels, recommendation lists and supermarkets — to consumers and supply chain intermediaries. It examined 17 organisations and key supermarkets that communicate on the sustainability of world fisheries and aquaculture products. Certification schemes assess a relatively small number of specific fisheries and indicate sustainability through labels. Recommendation lists cover more species and areas but in less detail. FAO guidelines for fisheries ecolabelling and aquaculture certification constituted the benchmarks with which improving conformance was found. However, significant variation in fisheries’ assessment exists, affecting the accuracy and precision of information and advice provided. Inconsistent approaches and contradictory advice among certification schemes and recommendation lists potentially increase consumer confusion and reduce their credibility. The review identifies seven critical attributes schemes must address — scope, accuracy, independence, precision, transparency, standardisation and cost-effectiveness — and recommends that certification schemes and recommendation lists enhance their consistency and credibility through compliance with these attributes and FAO guidelines. Fish sustainability information schemes play an important role in securing a sustainable future for the oceans. Uptake of this review’s recommendations should reduce consumer confusion and increase confidence in the benefits of sustainable purchasing

Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous CD8+ T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation - pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with CD4+ T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy

An assessment of early colonisation of implant-abutment metal surfaces by single species and co-cultured bacterial periodontal pathogens

Objective Numerous studies have proposed that smooth metal surfaces reduce initial bacterial attachment in the establishment of an early biofilm formation. However, these studies have largely examined single bacterial species, which are not always relevant as pathogens identified as initiators of inflammatory peri-implantitis. This study investigated the adherence of four periodontally-relevant bacterial species to implant and abutment surfaces in current clinical use. Methods Discs of polished cobalt chromium (CoCr-polished) and milled titanium (Ti-milled), representing two clinically relevant surfaces, were prepared and surfaces were characterised. Bacterial species Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were cultured to mid-log or stationary growth phase. Co-cultures of P. gingivalis, F. nucleatum and P. gingivalis, F. nucleatum, Pr. intermedia were similarly prepared. Bacteria were inoculated onto discs for 2 h, stained with a live/dead fluorescent stain and percentage bacterial coverage was calculated by confocal microscopy and image analysis. Results CoCr-polished discs had smooth surfaces with gentle valley structures, whilst Ti-milled discs had sharp edged peaks. Both discs demonstrated a partial wetting ability capable of initiating bacterial adhesion. P. gingivalis, F. nucleatum and co-cultures, at both mid-log and stationary concentrations, demonstrated equally high coverage of both the smooth CoCr-polished and the rougher Ti-milled metal surfaces. Pr. intermedia and A. actinomycetemcomitans demonstrated lower surface coverage which was slightly higher for Ti-milled. Conclusion Variability was noted in the adherence potential for the respective periodontal pathogens examined. Particularly high adherence was noted for P. gingivalis and F. nucleatum, despite the manufacture of a smooth surface. Clinical significance Both surfaces studied may be used at implant-abutment junctions and both possess an ability to establish a bacterial biofilm containing a periodontally-relevant species. These surfaces are thus able to facilitate the apical migration of bacteria associated with peri-implantitis

Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway

The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFb1 reduces production of proinflammatory cytokines, including TNFa, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses