Population genetic studies can be useful for informing conservation and management. In Atlantic salmon, Salmo salar L., population structuring frequently occurs between river systems, but contrasting ...patterns occur within rivers, highlighting the need for catchment‐specific studies to inform management. Here, population structure of Atlantic salmon was examined in the River Tamar, United Kingdom, using 12 microsatellite loci. Gene diversity and allelic richness ranged from 0.80 to 0.84 and from 8.96 to 10.24, respectively. Some evidence of genetic structure was found, including significant genetic differentiation between samples in different subcatchments (pairwise θ and tests of genic differentiation), results from assignment tests and a pattern of isolation by distance. Conversely, structure revealed only one population cluster, and an analysis of molecular variance showed no significant variation between subcatchments. Evidence of population bottlenecks depended on the mutation model assumed and is discussed with reference to catchment‐specific studies of stock abundance. Implications for implementing management actions are considered.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors ...include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10(-11), OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.
The ability of the GABA
A-receptor-subtype-selective hypnotic zaleplon to produce physical dependence was compared to the nonselective benzodiazepine triazolam. Progressively increasing doses of ...zaleplon and triazolam were given to baboons by intragastric infusion once each day, with doses increasing every 17 days. Next, the highest dose was given for 10–34 additional days by continuous infusion. Both drugs produced increases in food-maintained lever pressing, ataxia, and time to complete a fine motor task. Plasma levels increased dose-dependently; drug was detectable 24 h after higher doses. Flumazenil produced a mild or intermediate precipitated-withdrawal syndrome on day 14 of all dosing conditions. When drug delivery ended after 85–100 days, a benzodiazepine-type withdrawal syndrome occurred. Physical dependence potential of zaleplon and triazolam appear similar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Study objectives: (1) To evaluate the development of clinical governance within public health departments. (2) To assess two models for examining clinical governance in public health departments. ...Design: Semi-structured interviews carried out during the annual visits of the regional director of public health to the health authority public health departments. Setting: West Midland Region, England. Participants: Directors of public health plus other members of public health departments. Main results: These visits demonstrated that there is already a substantial amount of clinical governance activity taking place in the region's public health departments. There was also a need to reclassify many routinely occurring activities and include them under the clinical governance heading. Conclusions: The two models both proved useful for examining clinical governance in public health departments, however combining them into a matrix provided the best results. This matrix will still be useful after the reorganisation of the NHS and could be used to assess any public health department in the world. The West Midland public health departments find the visits valuable as they provide a source of external peer review of their activities. The public health departments have ownership of the process.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Antibodies binding to double‐stranded (ds) DNA are strongly associated with renal involvement in patients with systemic lupus erythematosus (SLE). We have generated two new IgG DNA‐binding monoclonal ...antibodies (mAb), RH‐14 and DIL‐6, from the peripheral blood lymphocytes of two SLE patients with glomerulonephritis using the heteromyeloma cell line CB‐F7. RH‐14 is an IgG1 λ antibody which also bound to single‐stranded (ss)DNA, histones and nucleosomes. DIL‐6 is an IgG3 λ antibody with restricted antigen binding specificity. cDNA encoding the variable regions of the heavy (VH) and light (VL) chains of RH‐14 was sequenced and the antigen binding site of this mAb was computer modelled. Sequence analysis of VH and VL regions of RH‐14 showed that VH is derived from germ‐line gene V3‐7, a member of the VH3 family, and VL is derived from DPL 11, a member of the Vλ2 family. Somatic mutations and basic amino acid residues are identified in the complementarity‐ determining regions of both VH and VL regions. The nephritogenic properties of these mAb were analyzed by implanting and growing the hybridoma cells secreting the mAb in the peri toneum of SCID mice. The animals that received the RH‐14 hybridoma produced higher levels of proteinuria (3 to ≥ 4) (p < 0.001) compared to the groups that received DIL‐6 (trace to ≥ 1) or CB‐F7 (trace). Electron microscopy of kidney sections from all the RH‐14‐ implanted animals showed granular immunoglobulin deposition in the renal glomerular capil laries and mesangium. In this study we have shown for the first time using electron micros copy that a human IgG anti‐dsDNA mAb, RH‐14, is nephritogenic and that deposition of such an antibody alone is sufficient to induce renal damage.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The spin-probe detected polarity index H(25 °C) of SDS micelles decreases linearly with the number of inserted sugar-based nonionic surfactant molecules. This decrease is interpreted as being due to ...the expulsion of water molecules by the sugar groups from the polar shell surrounding the hydrocarbon core of the dodecyl micelle. Employing the geometrical model described in the companion paper immediately preceding this work, the effective volume of water expulsion is found to be similar to the volume of the sugar groups after taking into account that the OH bonds of the sugar groups also contribute to the polarity index H(25 °C). The estimate of the hydration of pure SDS micelles as a function of their aggregation number from these studies with the spin probe 16 doxylstearic acid methyl ester is similar to that with 5 doxylstearic acid methyl ester. This confirms that both spin probes are located similarly in the polar shell.
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IJS, KILJ, NUK, PNG, UL, UM
Study objective In 1996, the Food and Drug Administration and the Department of Health and Human Services enacted rules allowing a narrow exception from informed consent for critically ill patients ...enrolled in emergency research. These include requirements for community consultation prior to trial implementation. Previous studies have noted difficulty in engaging the community. We seek to describe the experience with random dialing surveys as a tool for community consultation across 5 metropolitan regions in the United States. Methods Random dialing surveys were used as part of the community consultation for an out-of-hospital clinical trial sponsored by the Resuscitation Outcomes Consortium. The survey method was designed to obtain a representative sample of the community according to population demographics and geography. Logistics of survey administration, role of the survey in community consultation, and survey results by population demographics are discussed. Results Random dialing surveys were conducted in 5 of 8 US Resuscitation Outcomes Consortium sites. Overall, 70% to 79% of respondents indicated they would be willing to be enrolled in this study. Support for the inclusion of children (aged 15 to 18 years) ranged from 52% to 71%. Respondents aged 18 to 34 years were more willing to participate in the trial than older age groups. Women and racial minorities were less likely to favor the inclusion of minors. Conclusion Random dialing surveys provide an additional tool to engage the community and obtain a sample of the opinion of the population about research conducted under the emergency exception from informed consent regulations. Similar results were obtained across 5 diverse communities in the United States.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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