Deploy diverse renewables to save tropical rivers.

A strategic mix of solar, wind and storage technologies around river basins would be safer and cheaper than building large dams, argue Rafael J. P. Schmitt, Noah Kittner and colleagues

Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany

Objectives: This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods: Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results: 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions: Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT

Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

<p>Abstract</p> <p>Background</p> <p>Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA) on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women.</p> <p>Methods</p> <p>A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-matched control subjects (43.1% African-American). Neuroserpin single nucleotide polymorphisms (SNPs) chosen through HapMap were genotyped in the study population and assessed for association with stroke.</p> <p>Results</p> <p>Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42) of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT) among Caucasians (OR = 2.05, p = 0.023) but not African-Americans (OR = 0.71, p = 0.387). Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only.</p> <p>Conclusion</p> <p>This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.</p

Cross-sector storage and modeling needed for deep decarbonization

As many researchers work to achieve a decarbonized grid, there is a general appreciation that we need to model the total energy system, but that doing so is difficult, if not impractical. Studies may focus on one piece of the grid and reach a conclusion whether a particular approach will or won’t work. Including cross-sector storage in modeling provides opportunities to enable solutions that are otherwise impossible to identify and that may become the key to reaching a lowest-cost, lowest-carbon energy system

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli

Incidence of first stroke and ethnic differences in stroke pattern in Bradford, UK: Bradford Stroke Study

Background: Information on ethnic disparities in stroke between White and Pakistani population in Europe is scarce. Bradford District has the largest proportion of Pakistani people in England; this provides a unique opportunity to study the difference in stroke between the two major ethnic groups. Aim: To determine the first-ever-stroke incidence and examine the disparities in stroke patterns between Whites and Pakistanis in Bradford. Methods: Prospective 12 months study consisting of 273,327 adults (≥18 years) residents. Stroke cases were identified by multiple overlapping approaches. Results: In the study period, 541 first-ever-strokes were recorded. The crude incidence rate was 198 per 100,000 person-years. Age adjusted-standardized rate to the World Health Organization world population of first-ever-stroke is 155 and 101 per 100,000 person-years in Pakistanis and Whites respectively. Four hundred and thirty-eight patients (81%) were Whites, 83 (15.3%) were Pakistanis, 11 (2%) were Indian and Bangladeshis, and 9 (1.7%) were of other ethnic origin. Pakistanis were significantly younger and had more obesity (p = 0.049), and diabetes mellitus (DM) (p = <0.001). They were less likely to suffer from atrial fibrillation (p = <0.001), be ex- or current smokers (p = <0.001), and drink alcohol above the recommended level (p = 0.007) compared with Whites. In comparison with Whites, higher rates of age-adjusted stroke (1.5-fold), lacunar infarction (threefold), and ischemic infarction due to large artery disease (twofold) were found in the Pakistanis. Conclusions: The incidence of first-ever-stroke is higher in the Pakistanis compared with the Whites in Bradford, UK. Etiology and vascular risk factors vary between the ethnic groups. This information should be considered when investigating stroke etiology, and when planning prevention and care provision to improve outcomes after stroke

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes