Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts

Virulence of Malaria Is Associated with Differential Expression of Plasmodium falciparum var Gene Subgroups in a Case-Control Study

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by ∼60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcript

A matched-pair cluster design study protocol to evaluate implementation of the Canadian C-spine rule in hospital emergency departments: Phase III

BACKGROUND: Physicians in Canadian emergency departments (EDs) annually treat 185,000 alert and stable trauma victims who are at risk for cervical spine (C-spine) injury. However, only 0.9% of these patients have suffered a cervical spine fracture. Current use of radiography is not efficient. The Canadian C-Spine Rule is designed to allow physicians to be more selective and accurate in ordering C-spine radiography, and to rapidly clear the C-spine without the need for radiography in many patients. The goal of this phase III study is to evaluate the effectiveness of an active strategy to implement the Canadian C-Spine Rule into physician practice. Specific objectives are to: 1) determine clinical impact, 2) determine sustainability, 3) evaluate performance, and 4) conduct an economic evaluation. METHODS: We propose a matched-pair cluster design study that compares outcomes during three consecutive 12-months "before," "after," and "decay" periods at six pairs of "intervention" and "control" sites. These 12 hospital ED sites will be stratified as "teaching" or "community" hospitals, matched according to baseline C-spine radiography ordering rates, and then allocated within each pair to either intervention or control groups. During the "after" period at the intervention sites, simple and inexpensive strategies will be employed to actively implement the Canadian C-Spine Rule. The following outcomes will be assessed: 1) measures of clinical impact, 2) performance of the Canadian C-Spine Rule, and 3) economic measures. During the 12-month "decay" period, implementation strategies will continue, allowing us to evaluate the sustainability of the effect. We estimate a sample size of 4,800 patients in each period in order to have adequate power to evaluate the main outcomes. DISCUSSION: Phase I successfully derived the Canadian C-Spine Rule and phase II confirmed the accuracy and safety of the rule, hence, the potential for physicians to improve care. What remains unknown is the actual change in clinical behaviors that can be affected by implementation of the Canadian C-Spine Rule, and whether implementation can be achieved with simple and inexpensive measures. We believe that the Canadian C-Spine Rule has the potential to significantly reduce health care costs and improve the efficiency of patient flow in busy Canadian EDs

Life cycle assessment of European anchovy (Engraulis encrasicolus) landed by purse seine vessels in northern Spain

Purpose: The main purpose of this article is to assess the environmental impacts associated with the fishing operations related to European anchovy fishing in Cantabria (northern Spain) under a life cycle approach. Methods: The life cycle assessment (LCA) methodology was applied for this case study including construction, maintenance, use, and end of life of the vessels. The functional unit used was 1 kg of landed round anchovy at port. Inventory data were collected for the main inputs and outputs of 32 vessels, representing a majority of vessels in the fleet. Results and discussion: Results indicated, in a similar line to what is reported in the literature, that the production, transportation, and use of diesel were the main environmental hot spots in conventional impact categories. Moreover, in this case, the production and transportation of seine nets was also relevant. Impacts linked to greenhouse gas (GHG) emissions suggest that emissions were in the upper range for fishing species captured with seine nets and the value of global warming potential (GWP) was 1.44 kg CO2 eq per functional unit. The ecotoxicity impacts were mainly due to the emissions of antifouling substances to the ocean. Regarding fishery-specific categories, many were discarded given the lack of detailed stock assessments for this fishery. Hence, only the biotic resource use category was computed, demonstrating that the ecosystems' effort to sustain the fishery is relatively low. Conclusions: The use of the LCA methodology allowed identifying the main environmental hot spots of the purse seining fleet targeting European anchovy in Cantabria. Individualized results per port or per vessel suggested that there are significant differences in GHG emissions between groups. In addition, fuel use is high when compared to similar fisheries. Therefore, research needs to be undertaken to identify why fuel use is so high, particularly if it is related to biomass and fisheries management or if skipper decisions could play a role.The authors thank the Ministry of Economy and Competitiveness of the Spanish Government for their financial support via the project GeSAC-Conserva: Sustainable Management of the Cantabrian Anchovies (CTM2013-43539-R) and to Pedro Villanueva-Rey for valuable scientific exchange. Jara Laso thanks the Ministry of Economy and Competitiveness of Spanish Government for their financial support via the research fellowship BES-2014-069368 and to the Ministry of Rural Environment, Fisheries and Food of Cantabria for the data support. Dr. Ian Vázquez-Rowe thanks the Peruvian LCA Network for operational support. Reviewers are also thanked for the valuable and detailed suggestions. The work of Dr. Rosa M. Crujeiras has been funded by MTM2016-76969P (AEI/FEDER, UE)

Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes

The syndromes caused by frontotemporal lobar degeneration (FTLD) have highly heterogenous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the last decade, but we propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, we examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia (bvFTD), the non-fluent (nfvPPA), semantic (svPPA) variants of primary progressive aphasia, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We also included patients with logopenic primary progressive aphasia (lvPPA) and those who met criteria for PPA but not one of the three subtypes. To date, forty-nine patients have a neuropathological diagnosis. A principal component analysis identified symptom dimensions that broadly recapitulated the core features of the main clinical syndromes. However, the subject-specific scores on these dimensions showed considerable overlap across the diagnostic groups. Sixty-two percent of participants had phenotypic features that met the diagnostic criteria for more than one syndrome. Behavioural disturbance was prevalent in all groups. Forty-four percent of patients with CBS had PSP-like features and thirty percent of patients with PSP had CBS-like features. Many patients with PSP and CBS had language impairments consistent with nfvPPA while patients with bvFTD often had semantic impairments. Using multivariate source-based morphometry on a subset of patients (n=133), we identified patterns of co-varying brain atrophy that were represented across the diagnostic groups. Canonical correlation analysis of clinical and imaging components found three key brain-behaviour relationships that revealed a continuous spectrum across the cohort rather than discrete diagnostic entities. In the forty-six patients with longitudinal follow up (mean 3.6 years) syndromic overlap increased with time. Together, these results show that syndromes associated with FTLD do not form discrete mutually exclusive categories from their clinical features or structural brain changes, but instead exist in a multidimensional spectrum. Patients often manifest diagnostic features of multiple disorders and deficits in behaviour, movement and language domains are not confined to specific diagnostic groups. It is important to recognise individual differences in clinical phenotype, both for clinical management and to understand pathogenic mechanisms. We suggest that the adoption of a transdiagnostic approach to the spectrum of FTLD syndromes provides a useful framework with which to understand disease progression, heterogeneity and treatment.This work was funded by the Holt Fellowship (AGM), British Academy (KAT, PF160048), Wellcome Trust (JBR, 103838), the PSP Association, the Medical Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre and Cambridge Brain Bank; and the Cambridge Centre for Parkinson Plus

Transjugular intrahepatic portosystemic stent-shunts: a new option in portal hypertension.

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.</jats:p