Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis

&lt;p&gt;A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis &quot;infectome.&quot; These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.&lt;/p&gt;</p

2d Gauge Theories and Generalized Geometry

We show that in the context of two-dimensional sigma models minimal coupling of an ordinary rigid symmetry Lie algebra $\mathfrak{g}$ leads naturally to the appearance of the "generalized tangent bundle" $\mathbb{T}M \equiv TM \oplus T^*M$ by means of composite fields. Gauge transformations of the composite fields follow the Courant bracket, closing upon the choice of a Dirac structure $D \subset \mathbb{T}M$ (or, more generally, the choide of a "small Dirac-Rinehart sheaf" $\cal{D}$), in which the fields as well as the symmetry parameters are to take values. In these new variables, the gauge theory takes the form of a (non-topological) Dirac sigma model, which is applicable in a more general context and proves to be universal in two space-time dimensions: A gauging of $\mathfrak{g}$ of a standard sigma model with Wess-Zumino term exists, \emph{iff} there is a prolongation of the rigid symmetry to a Lie algebroid morphism from the action Lie algebroid $M \times \mathfrak{g}\to M$ into $D\to M$ (or the algebraic analogue of the morphism in the case of $\cal{D}$). The gauged sigma model results from a pullback by this morphism from the Dirac sigma model, which proves to be universal in two-spacetime dimensions in this sense.Comment: 22 pages, 2 figures; To appear in Journal of High Energy Physic

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

Diffusion of Subsidized ACTs in Accredited Drug Shops in Tanzania: Determinants of Stocking and Characteristics of Early and Late Adopters.

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers

What is the evidence for the management of patients along the pathway from the emergency department to acute admission to reduce unplanned attendance and admission? An evidence synthesis

Background Globally, the rate of emergency hospital admissions is increasing. However, little evidence exists to inform the development of interventions to reduce unplanned Emergency Department (ED) attendances and hospital admissions. The objective of this evidence synthesis was to review the evidence for interventions, conducted during the patient’s journey through the ED or acute care setting, to manage people with an exacerbation of a medical condition to reduce unplanned emergency hospital attendance and admissions. Methods A rapid evidence synthesis, using a systematic literature search, was undertaken in the electronic data bases of MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science, for the years 2000–2014. Evidence included in this review was restricted to Randomised Controlled Trials (RCTs) and observational studies (with a control arm) reported in peer-reviewed journals. Studies evaluating interventions for patients with an acute exacerbation of a medical condition in the ED or acute care setting which reported at least one outcome related to ED attendance or unplanned admission were included. Results Thirty papers met our inclusion criteria: 19 intervention studies (14 RCTs) and 11 controlled observational studies. Sixteen studies were set in the ED and 14 were conducted in an acute setting. Two studies (one RCT), set in the ED were effective in reducing ED attendance and hospital admission. Both of these interventions were initiated in the ED and included a post-discharge community component. Paradoxically 3 ED initiated interventions showed an increase in ED re-attendance. Six studies (1 RCT) set in acute care settings were effective in reducing: hospital admission, ED re-attendance or re-admission (two in an observation ward, one in an ED assessment unit and three in which the intervention was conducted within 72 h of admission). Conclusions There is no clear evidence that specific interventions along the patient journey from ED arrival to 72 h after admission benefit ED re-attendance or readmission. Interventions targeted at high-risk patients, particularly the elderly, may reduce ED utilization and warrant future research. Some interventions showing effectiveness in reducing unplanned ED attendances and admissions are delivered by appropriately trained personnel in an environment that allows sufficient time to assess and manage patients

Eye movements and brain oscillations to symbolic safety signs with different comprehensibility

Background: The aim of this study was to investigate eye movements and brain oscillations to symbolic safety signs with different comprehensibility. Methods: Forty-two young adults participated in this study, and ten traffic symbols consisting of easy-to-comprehend and hard-to-comprehend signs were used as stimuli. During the sign comprehension test, real-time eye movements and spontaneous brain activity [electroencephalogram (EEG) data] were simultaneously recorded. Results: The comprehensibility level of symbolic traffic signs significantly affects eye movements and EEG spectral power. The harder to comprehend the sign is, the slower the blink rate, the larger the pupil diameter, and the longer the time to first fixation. Noticeable differences on EEG spectral power between easy-to-comprehend and hard-to-comprehend signs are observed in the prefrontal and visual cortex of the human brain. Conclusions: Sign comprehensibility has significant effects on real-time nonintrusive eye movements and brain oscillations. These findings demonstrate the potential to integrate physiological measures from eye movements and brain oscillations with existing evaluation methods in assessing the comprehensibility of symbolic safety signs.open

Randomised short-term trial of high-span versus low-span APAP for treating sleep apnoea

PURPOSE: Auto-titrating continuous positive airway pressure (APAP) devices were developed to improve treatment efficacy and compliance in patients with obstructive sleep apnoea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed to compare the adherence, efficacy and tolerability of treatment with high-span versus low-span APAP. METHODS: Seventy-six newly diagnosed OSAS patients fulfilling the treatment criteria were randomised to receive high-span (HS, range 4-15cmH2O, n?=?38) or low-span (LS, range 8-12cmH2O, n?=?38) APAP. Patients were assessed at 1 and 3 months. RESULTS: Median Epworth sleepiness scale (ESS) was 13 (IQR, 6-16) and median apnoea-hypopnoea index (AHI) was 35.9 (IQR, 27.6-56.3). There were no significant differences in baseline demographic and clinical characteristics between groups. Overall, no significant differences were found at the first month assessment. After 3 months of therapy, we found again no differences in residual AHI or ESS. However, the group HS proved less adherent than group LS, respectively, with median 87 % (IQR, 60.5-97.5) versus 94 % (IQR, 80.0-98.3) of the nights using =4 h (P?=?0.014) and mean (±SD) usage 5.7?±?1.6 versus 6.4?±?1.2 h/night (P?=?0.049). The group HS reported more frequently nasal congestion, excessive oronasal dryness and nocturnal awakenings of at least moderate intensity, the latter with statistical significance (P?=?0.005). CONCLUSIONS: Both pressure ranges appear to be equally effective to correct AHI and to improve symptoms. Though, patients with high-span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.T Pinto has received financial support from Linde and Vitalaire (Healthcare Providers) for attending symposia and honoraria for speaking at symposia from Philips. After the conclusion of the study, JC Winck has started working in a global position for Linde. The remaining authors declare that they have no conflict of interest