Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Population dynamics of Scyllarid lobsters of the genus Thenus spp. on the Queensland (Australia) east coast. I. Assessing the effects of tagging

The effect of different combinations of tagging and release methods was examined on the survival, moulting, growth increment and recapture rates of slipper lobsters Thenus spp. on the Queensland (Australia) east coast using generalised linear modelling methods. Laboratory experiments indicated that while tagging is unlikely to significantly affect the survival rate or growth increments of lobsters, it is likely to lower the incidence of moulting. In the field, recapture rates of tagged lobsters increased markedly by applying an antibiotic/antifungal ointment to the tag wound and by minimising the length of time lobsters were held on board prior to release. Recapture rates for Thenus orientalis declined by about 0.5% for every hour lobsters were held on board prior to release, even though they were kept in aerated seawater. About twice as many male T. orientalis were recaptured compared to females. Reasons for this may be related to size differences between the sexes and how the fishers valued the rewards for different size classes. The size of the T-bar anchor tag affected recapture rates of Thenus indicus; recapture rates of lobsters tagged with small tags were about 33% higher than those with large tags. Two different methods of release were also compared; surface release and bottom cage release. Recapture rates of large lobsters and those that were held on board for several hours prior to release were improved by using the bottom cage method. However, under some conditions, the cage may lower recapture rates relative to the surface release method, possibly because of increased stress and trauma from crowding in the cage. For both species, growth increments of recaptured lobsters increased with the period at liberty and declined with increasing lobster size. Females had significantly larger growth increments than males

Population dynamics of Scyllarid lobsters of the genus Thenus spp. on the Queensland (Australia) east coast. I. Assessing the effects of tagging

The effect of different combinations of tagging and release methods was examined on the survival, moulting, growth increment and recapture rates of slipper lobsters Thenus spp. on the Queensland (Australia) east coast using generalised linear modelling methods. Laboratory experiments indicated that while tagging is unlikely to significantly affect the survival rate or growth increments of lobsters, it is likely to lower the incidence of moulting. In the field, recapture rates of tagged lobsters increased markedly by applying an antibiotic/antifungal ointment to the tag wound and by minimising the length of time lobsters were held on board prior to release. Recapture rates for Thenus orientalis declined by about 0.5% for every hour lobsters were held on board prior to release, even though they were kept in aerated seawater. About twice as many male T. orientalis were recaptured compared to females. Reasons for this may be related to size differences between the sexes and how the fishers valued the rewards for different size classes. The size of the T-bar anchor tag affected recapture rates of Thenus indicus; recapture rates of lobsters tagged with small tags were about 33% higher than those with large tags. Two different methods of release were also compared; surface release and bottom cage release. Recapture rates of large lobsters and those that were held on board for several hours prior to release were improved by using the bottom cage method. However, under some conditions, the cage may lower recapture rates relative to the surface release method, possibly because of increased stress and trauma from crowding in the cage. For both species, growth increments of recaptured lobsters increased with the period at liberty and declined with increasing lobster size. Females had significantly larger growth increments than males

A quantitative method for staging penaeid prawn ovaries using image analysis

A quantitative method of staging reproductive development based on the use of cell measurements and computerized image analysis of histological sections is described. The method has been applied to samples of eastern king prawn, Penaeus plebejus, collected in Queensland, Australia. Luminance measurements of selected tissue structures within the ovary were used to determine three luminance ranges which characterized ovarian development in histological sections. Cell diameter, average luminance and percent area of an ovary section within a luminance range of 200–245 were the most useful variables to discriminate between the different ovarian developmental stages. Discriminant analysis successfully separated maturing, mature and resorbing groups in 94% of the samples, but discrimination of stages within the above groups was as low as 30%. The estimated discriminant functions suggest there is a continuum of development which can be characterized by a combination of measurements obtained from histological sections

Maturation in the female eastern king prawn Penaeus plebejus from coastal waters of eastern Australia, and considerations for quantifying egg production in penaeid prawns

The trawl fishery for eastern king prawns, Penaeus plebejus, is of major commercial significance on the east coast of Australia. This paper describes the reproductive biology of female P. plebejus and presents new information relevant to quantifying egg production in penaeid prawn populations. The study concluded that the gonosomatic index (GSI) covaried with prawn size and was, therefore, likely to be a poor indicator of reproductive activity for penaeid prawn populations. GSI was also found to be not independent of ovary histological stage, moult stage, insemination status and parasitisation by bopyrid isopods. An histological description of ovarian development and the incidence of each stage of development is provided. This includes a description of the ovulation stage, which has not been previously recorded in naturally-occurring populations. Fifty percent of female P. plebejus were classed as mature at 42mm CL. The relationships between GSI, percent mature, and percent inseminated with size suggest that there is a decline in the capacity of large (> 60 mm CL) females to produce and fertilise eggs. The declines in both GSI and percent mature is indicative of ovarian senescence in large(o1d) females, which has not been recorded previously in penaeid prawns. An index which considers the relationships between the percent mature, fecundity and the percent inseminated with size, as well as the influence of mortality on the population, is put forward to determine the relative contribution of different size classes of females to egg production. The index suggests that females >50 mm CL contribute little to egg production, and that the bulk of eggs are produced by 35 to 48 mm CL females

Extending Wavelet Filters. Infinite Dimensions, the Non-Rational Case, and Indefinite-Inner Product Spaces

In this paper we are discussing various aspects of wavelet filters. While there are earlier studies of these filters as matrix valued functions in wavelets, in signal processing, and in systems, we here expand the framework. Motivated by applications, and by bringing to bear tools from reproducing kernel theory, we point out the role of non-positive definite Hermitian inner products (negative squares), for example Krein spaces, in the study of stability questions. We focus on the nonrational case, and establish new connections with the theory of generalized Schur functions and their associated reproducing kernel Pontryagin spaces, and the Cuntz relations

Local or general anesthesia for open hernia repair: a randomized trial

&lt;b&gt;Objective&lt;/b&gt;: To compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial. &lt;b&gt;Summary Background Data&lt;/b&gt;: LA hernia repair is thought to be safer for patients, causes less postoperative pain, cost less, and is associated with a more rapid recovery when compared with the same operation performed under GA. &lt;b&gt;Methods&lt;/b&gt;: All patients presenting to three surgeons during the study period with a primary groin hernia were considered eligible. Outcome parameters measured including tests of vigilance, divided attention, sustained attention, memory, cognitive function, pain, return to normal activity, and costs. &lt;b&gt;Results&lt;/b&gt;: Two hundred seventy-nine patients were randomized to LA or GA hernia repair; 276 of these had an operation, with 138 participants in each group. At 6, 24, and 72 hours postoperatively there were no differences in vigilance or divided attention between the groups. Similarly, memory, sustained attention, and cognitive function were not impaired in either group. Although physical activity was significantly impaired at 24 hours, this and return to usual social activities were similar in both groups. While patients in the LA group had significantly less pain on moving, at 6 hours they were less likely to recommend the same operation to someone else. GA hernia repair cost 4% more than the same operation under LA. &lt;b&gt;Conclusions&lt;/b&gt;: There are no major differences in patient recovery after LA or GA hernia repair. Patients should be offered a choice of anesthesia, LA or GA, for repair of their groin hernia. There has been a renewed interest in the use of local anesthesia (LA) for inguinal hernia repair. This has been brought about by the rapid introduction of tension-free hernioplasty, which is thought to be easier to perform than conventional methods of hernia repair. 1 The advantages claimed for the use of LA include increased safety for patients, better postoperative pain control, shorter recovery period, and reduced cost when compared with hernia repair performed under general anesthesia (GA). It is not possible to assess differences in safety between LA and GA hernia repair as mortality and serious cardiovascular events are so low following this procedure. 2 GA, however, has been thought to have a significant effect on psychomotor skills, attention, and memory in the postanesthesia period. Some authors have suggested this effect may be long term and related to cerebral ischemia. 3 This is thought to be particularly the case in elderly patients with significant comorbid disease. Given that local anesthetics have little or no serious CNS effects, one might anticipate that their use would be associated with better outcomes in terms of cognitive function. We report a randomized clinical trial comparing LA and GA open hernia repair