The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review

Background: Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. Methods: Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. Results: We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14–.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. Conclusions: Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection

NMR Experiments on a Three-Dimensional Vibrofluidized Granular Medium

A three-dimensional granular system fluidized by vertical container vibrations was studied using pulsed field gradient (PFG) NMR coupled with one-dimensional magnetic resonance imaging (MRI). The system consisted of mustard seeds vibrated vertically at 50 Hz, and the number of layers N_ell <= 4 was sufficiently low to achieve a nearly time-independent granular fluid. Using NMR, the vertical profiles of density and granular temperature were directly measured, along with the distributions of vertical and horizontal grain velocities. The velocity distributions showed modest deviations from Maxwell-Boltzmann statistics, except for the vertical velocity distribution near the sample bottom which was highly skewed and non-Gaussian. Data taken for three values of N_ell and two dimensionless accelerations Gamma=15,18 were fit to a hydrodynamic theory, which successfully models the density and temperature profiles including a temperature inversion near the free upper surface.Comment: 14 pages, 15 figure

Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes

Schistosome parasites are a major cause of disease in the developing world, but the mechanism by which these parasites first infect their host has been studied at the molecular level only for S. mansoni. In this paper, we have mined recent genome annotations of S. mansoni and S. japonicum, a zoonotic schistosome species, to identify differential expansion of peptidase gene families that may be involved in parasite invasion and subsequent migration through skin. Having identified a serine peptidase gene family in S. mansoni and a cysteine peptidase gene family in S. japonicum, we then used a comparative proteomic approach to identify potential substrates of representative members of both classes of enzymes from S. mansoni in human skin. The results of this study suggest that while these species evolved to use different classes of peptidases in host invasion, both are capable of cleaving components of the epidermis and dermal extracellular matrix, as well as proteins involved in the host immune response against the migrating parasite

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Abstract Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing