The UK risk assessment scheme for all non-native species

1. A pest risk assessment scheme, adapted from the EPPO (European and Mediterranean Plant Protection Organisation) scheme, was developed to assess the risks posed to UK species, habitats and ecosystems by non-native taxa. 2. The scheme provides a structured framework for evaluating the potential for non-native organisms, whether intentional or unintentional introductions, to enter, establish, spread and cause significant impacts in all or part of the UK. Specialist modules permit the relative importance of entry pathways, the vulnerability of receptors and the consequences of policies to be assessed and appropriate risk management options to be selected. Spreadsheets for summarising the level of risk and uncertainty, invasive attributes and economic impact were created. In addition, new methods for quantifying economic impact and summarising risk and uncertainty were explored. 3. Although designed for the UK, the scheme can readily be applied elsewhere

Observed photodetachment in parallel electric and magnetic fields

We investigate photodetachment from negative ions in a homogeneous 1.0-T magnetic field and a parallel electric field of approximately 10 V/cm. A theoretical model for detachment in combined fields is presented. Calculations show that a field of 10 V/cm or more should considerably diminish the Landau structure in the detachment cross section. The ions are produced and stored in a Penning ion trap and illuminated by a single-mode dye laser. We present preliminary results for detachment from S- showing qualitative agreement with the model. Future directions of the work are also discussed.Comment: Nine pages, five figures, minor revisions showing final publicatio

Chlorine isotope behavior in subduction zone settings revealed by olivine-hosted melt inclusions from the Central America Volcanic Arc

Highlights • Chlorine isotopes were measured in melt inclusions along CAVA. • Melt inclusions have on average higher Cl than bulk rocks. • Aqueous fluids, melt-like component and metasomatized mantle form three distinct signatures. • The high Cl of the metasomatized mantle wedge suggests the presence of amphibole. • The amphibole signature in bulk rocks is diluted by late-stage processes. The isotopic composition of Cl, a highly hydrophilic and incompatible element, can provide new insights into the processes of element recycling in subduction zone settings. Samples from 13 localities in Guatemala, El Salvador, Nicaragua and Costa Rica, representing a ca. 1000 km long NW-SE segment along the Central American Volcanic Arc (CAVA), were selected. Ninety-seven melt inclusions, hosted by olivine Fo90−70, were measured for Cl isotope ratios and trace element concentrations. Melt inclusions from samples from Guatemala to northwest Nicaragua have a restricted range of Cl values (range 1‰, up to 3.8‰) and do not show any systematic variation along the arc. For some samples, the Cl in the melt inclusions is shifted by up to 2‰ to higher values compared to bulk rock data from the same volcanic center, for which the extent of Cl degassing is not known. The combination of Cl values in melt inclusions with trace elements and the existing knowledge about the slab contributions along the arc allows us to elucidate the Cl isotope composition of different endmembers in this subduction zone. From Guatemala to northwest Nicaragua, a fluid component, originating from serpentinite, has a Cl value close to +0.6‰. This value, similar to lithospheric serpentinites, confirms that despite the aqueous fluid migration through the entire slab, Cl isotopes do not fractionate significantly during transport. A melt-like component, present in the southern part of the arc, has negative Cl, possibly down to −2.5‰. This component has lower Cl than values of the oceanic crust but similar to sediments currently subducting beneath CAVA. Finally, a common component, most likely amphibole-bearing metasomatized mantle, is identified in samples with the highest Cl values (up to +3.0‰). The melting of amphibole, a mineral concentrating 37Cl over 35Cl, could explain the high Cl values. The difference between melt inclusions and bulk rock Cl in some volcanic centers probably results from late-stage processes such as mixing of different batches of magma at shallower levels after melt inclusions entrapment. Melt inclusions thus give a more comprehensive picture of Cl isotope systematics along the CAVA and in primitive subduction-related magmas

A 14-year experience with kidney transplantation.

Between November, 1962 and August, 1975, 668 kidney transplants were done in 556 consecutive patients at Denver, Colorado. The Denver experience has been divided into 7 periods of time, according to the conditions of care during each period. The results in related transplantation have changed little during the decade beginning in 1966. The results in unrelated transplantation have not materially changed since 1968. The long-term patient survival after related transplantation has been better than after cadaver transplantation. The results of transplantation in 57 children ages 3 to 18 years have been slightly better than the results of adult transplantation. The outcome of kidney transplantation and the feasibility of improving this therapy with present techniques are limited by our inability to accurately match each patient with the immunologically best donor and by our inability to precisely control the immune system of the recipient. Rejection is still the main reason for graft loss, and sepsis remains the main cause of patient mortality. More specific and less toxic means of achieving graft acceptance are needed before a higher level of patient service can be realized. However, even with the tools now available, thousands of recipients throughout the world have been returned to useful lives

Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: A pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk ofmajor cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regressionmodels to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genom