Transcriptome analysis of porcine M. semimembranosus divergent in intramuscular fat as a consequence of dietary protein restriction

peer-reviewedBackground: Intramuscular fat (IMF) content is positively correlated with aspects of pork palatability, including flavour, juiciness and overall acceptability. The ratio of energy to protein in the finishing diet of growing pigs can impact on IMF content with consequences for pork quality. The objective of this study was to compare gene expression profiles of Musculus semimembranosus (SM) of animals divergent for IMF as a consequence of protein dietary restriction in an isocaloric diet. The animal model was derived through the imposition of low or high protein diets during the finisher stage in Duroc gilts. RNA was extracted from post mortem SM tissue, processed and hybridised to Affymetrix porcine GeneChip® arrays. Results: IMF content of SM muscle was increased on the low protein diet (3.60 ± 0.38% versus 1.92 ± 0.35%). Backfat depth was also greater in animals on the low protein diet, and average daily gain and feed conversion ratio were lower, but muscle depth, protein content and moisture content were not affected. A total of 542 annotated genes were differentially expressed (DE) between animals on low and high protein diets, with 351 down-regulated and 191 up-regulated on the low protein diet. Transcript differences were validated for a subset of DE genes by qPCR. Alterations in functions related to cell cycle, muscle growth, extracellular matrix organisation, collagen development, lipogenesis and lipolysis, were observed. Expression of adipokines including LEP, TNFα and HIF1α were increased and the hypoxic stress response was induced. Many of the identified transcriptomic responses have also been observed in genetic and fetal programming models of differential IMF accumulation, indicating they may be robust biological indicators of IMF content. Conclusion: An extensive perturbation of overall energy metabolism in muscle occurs in response to protein restriction. A low protein diet can modulate IMF content of the SM by altering gene pathways involved in lipid biosynthesis and degradation; however this nutritional challenge negatively impacts protein synthesis pathways, with potential consequences for growth.Department of Agriculture, Food and the Marine, Ireland - Food Institutional Research Measur

Trends in HIV testing and recording of HIV status in the UK primary care setting: a retrospective cohort study 1995-2005

Objectives: To provide nationally representative data on trends in HIV testing in primary care and to estimate the proportion of diagnosed HIV positive individuals known to general practitioners (GPs). Methods: We undertook a retrospective cohort study between 1995 and 2005 of all general practices contributing data to the UK General Practice Research Database (GPRD), and data on persons accessing HIV care (Survey of Prevalent HIV Infections Diagnosed). We identified all practice-registered patients where an HIV test or HIV positive status is recorded in their general practice records. HIV testing in primary care and prevalence of recorded HIV positive status in primary care were estimated. Results: Despite 11-fold increases in male testing and 19-fold increases in non-pregnant female testing between 1995 and 2005, HIV testing rates remained low in 2005 at 71.3 and 61.2 tests per 100 000 person years for males and females, respectively, peaking at 162.5 and 173.8 per 100 000 person years at 25–34 years of age. Inclusion of antenatal tests yielded a 129-fold increase in women over the 10-year period. In 2005, 50.7% of HIV positive individuals had their diagnosis recorded with a lower proportion in London (41.8%) than outside the capital (60.1%). Conclusion: HIV testing rates in primary care remain low. Normalisation of HIV testing and recording in primary care in antenatal testing has not been accompanied by a step change in wider HIV testing practice. Recording of HIV positive status by GPs remains low and GPs may be unaware of HIV-related morbidity or potential drug interactions

Effect of Breed and Gender on Meat Quality of M. longissimus thoracis et lumborum Muscle from Crossbred Beef Bulls and Steers

peer-reviewedAbstract The objective of this study was to determine whether sire breed and/or castration had an effect on meat quality of M. longissimus thoracis et lumborum (LTL) muscle from crossbred bulls and steers and to investigate the relationship amongst the traits examined. Warner–Bratzler shear force (WBSF), intramuscular fat (IMF)%, cook-loss%, drip-loss%, colour (L*, a*, b*) and ultimate pH (upH) were determined in the LTL muscle from eight beef sire breeds representative of the Irish herd (Aberdeen Angus, Belgian Blue, Charolais, Hereford, Limousin, Parthenaise, Salers and Simmental). The results indicate that IMF%, cook-loss% and drip-loss% were associated with breed (p < 0.05); while WBSF, IMF% and cook-loss% differ between genders (p < 0.05). Steer LTL had a greater IMF% and exhibited reduced WBSF and cook-loss% in comparison to the bull LTL (p < 0.05). This study provides greater insight into how quality traits in beef are influenced by breed and gender and will support the industry to produce beef with consistent eating quality

WHAT TASKS TO AUTOMATE? AN INVESTIGATION OF WHAT TASKS MAKE SENSE TO AUTOMATE FOR FUTURE AVIATION PLATFORMS

The Army is developing a new generation of aircraft called Future Vertical Lift (FVL). These aircraft will integrate new technologies that change Army Aviation’s machinery, methods, and aircrew domains. Key to this effort is the development of automation to reduce pilot cognitive workload and prevent cognitive overload. The purpose of this research was to develop an understanding of the factors that influence pilot cognitive workload and to provide insight into what tasks make sense to automate for FVL. Researchers used a mixed methods approach, relying on scholarly literature and semi-structured interviews to elicit cognitive workload data from Army rotary-wing pilots. Researchers used the data from a simple and a complex MEDEVAC flight scenario to develop an influence diagram that models pilot cognitive workload based on influencing factors and subfactors. At a high level, the data indicate that pilot task demand and environmental factors have the most influence on cognitive workload during complex missions in challenging conditions. At a low level, the data indicate that light factors, intra-flight coordination, and task complexity are most influential on cognitive workload. The results suggest that tasks impacting these factors should be considered for automation to prevent pilot cognitive overload in FVL.DEVCOM AvMCCaptain, United States ArmyMajor, United States ArmyCaptain, United States ArmyMajor, United States ArmyApproved for public release. Distribution is unlimited

Primary care consultations and costs among HIV-positive individulas in UK primary care 1995-2005: a cohort study

Objectives: To investigate the role of primary care in the management of HIV and estimate primary care-associated costs at a time of rising prevalence. Methods: Retrospective cohort study between 1995 and 2005, using data from general practices contributing data to the UK General Practice Research Database. Patterns of consultation and morbidity and associated consultation costs were analysed among all practice-registered patients for whom HIV-positive status was recorded in the general practice record. Results: 348 practices yielded 5504 person-years (py) of follow-up for known HIV-positive patients, who consult in general practice frequently (4.2 consultations/py by men, 5.2 consultations/py by women, in 2005) for a range of conditions. Consultation rates declined in the late 1990s from 5.0 and 7.3 consultations/py in 1995 in men and women, respectively, converging to rates similar to the wider population. Costs of consultation (general practitioner and nurse, combined) reflect these changes, at £100.27 for male patients and £117.08 for female patients in 2005. Approximately one in six medications prescribed in primary care for HIV-positive individuals has the potential for major interaction with antiretroviral medications. Conclusion: HIV-positive individuals known in general practice now consult on a similar scale to the wider population. Further research should be undertaken to explore how primary care can best contribute to improving the health outcomes of this group with chronic illness. Their substantial use of primary care suggests there may be potential to develop effective integrated care pathways

Calibrating ensemble reliability whilst preserving spatial structure

Ensemble forecasts aim to improve decision-making by predicting a set of possible outcomes. Ideally, these would provide probabilities which are both sharp and reliable. In practice, the models, data assimilation and ensemble perturbation systems are all imperfect, leading to deficiencies in the predicted probabilities. This paper presents an ensemble post-processing scheme which directly targets local reliability, calibrating both climatology and ensemble dispersion in one coherent operation. It makes minimal assumptions about the underlying statistical distributions, aiming to extract as much information as possible from the original dynamic forecasts and support statistically awkward variables such as precipitation. The output is a set of ensemble members preserving the spatial, temporal and inter-variable structure from the raw forecasts, which should be beneficial to downstream applications such as hydrological models. The calibration is tested on three leading 15-d ensemble systems, and their aggregation into a simple multimodel ensemble. Results are presented for 12 h, 1° scale over Europe for a range of surface variables, including precipitation. The scheme is very effective at removing unreliability from the raw forecasts, whilst generally preserving or improving statistical resolution. In most cases, these benefits extend to the rarest events at each location within the 2-yr verification period. The reliability and resolution are generally equivalent or superior to those achieved using a Local Quantile-Quantile Transform, an established calibration method which generalises bias correction. The value of preserving spatial structure is demonstrated by the fact that 3×3 averages derived from grid-scale precipitation calibration perform almost as well as direct calibration at 3×3 scale, and much better than a similar test neglecting the spatial relationships. Some remaining issues are discussed regarding the finite size of the output ensemble, variables such as sea-level pressure which are very reliable to start with, and the best way to handle derived variables such as dewpoint depression

Gating-by-tilt of mechanosensitive membrane channels

We propose an alternative mechanism for the gating of biological membrane channels in response to membrane tension that involves a change in the slope of the membrane near the channel. Under biological membrane tensions we show that the energy difference between the closed (tilted) and open (untilted) states can far exceed kBT and is comparable to what is available under simple ilational gating. Recent experiments demonstrate that membrane leaflet asymmetries (spontaneous curvature) can strong effect the gating of some channels. Such a phenomenon would be more easy to explain under gating-by-tilt, given its novel intrinsic sensitivity to such asymmetry.Comment: 10 pages, 2 figure

Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study

Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. Trial Registration ClinicalTrials.gov NCT0054840