Prevalence of true vein graft aneurysms: Implications for aneurysm pathogenesis

AbstractBackground: Circumstantial evidence suggests that arterial aneurysms have a different cause than atherosclerosis and may form part of a generalized dilating diathesis. The aim of this study was to compare the rates of spontaneous aneurysm formation in vein grafts performed either for popliteal aneurysms or for occlusive disease. The hypothesis was that if arterial aneurysms form a part of a systemic process, then the rates of vein graft aneurysms should be higher for patients with popliteal aneurysms than for patients with lower limb ischemia caused by atherosclerosis. Methods: Infrainguinal vein grafting procedures performed from 1990 to 1995 were entered into a prospective audit and graft surveillance program. Aneurysmal change was defined as a focal increase in the graft diameter of 1.5 cm or greater, excluding false aneurysms and dilatations after graft angioplasty. Results: During the study period, 221 grafting procedures were performed in 200 patients with occlusive disease and 24 grafting procedures were performed in 21 patients with popliteal aneurysms. Graft surveillance revealed spontaneous aneurysm formation in 10 of the 24 bypass grafts (42%) for popliteal aneurysms but in only 4 of the 221 grafting procedures (2%) that were performed for chronic lower limb ischemia. Conclusion:This study provides further evidence that aneurysmal disease is a systemic process, and this finding has clinical implications for the treatment of popliteal aneurysms. (J Vasc Surg 1999;29:403-8.

Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease

AbstractPurpose: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta, which provide a potential therapeutic target for pharmacologic agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of doxycycline—an MMP inhibitor—to reduce matrix degradation was assessed in a previously described model of aneurysmal disease that used a brief pulse of elastase to induce MMP production and elastin degradation in arterial organ cultures. Methods: Porcine aortic segments (n = 8) were preincubated in exogenous pancreatic elastase for 24 hours before culture in standard conditions for 13 days with both 1 and 10 mg/L doxycycline. Control segments were cultured both without doxycycline and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereologic analysis of sections stained with Miller's elastin and van Gieson's stain. Results: Stereologic analysis demonstrated a significant preservation of elastin in aorta treated with doxycycline 10 mg/L (p < 0.001) and demonstrated that this preservation was accompanied by a significant reduction in MMP-9 activity (p < 0.02). Immunoblotting for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) showed no decreased production in the doxycycline-treated groups. Conclusions: Therapeutic ranges of doxycycline significantly inhibited elastin degradation and MMP-9 production within aortic organ cultures. These data suggest that doxycycline may have a potential application in reducing the growth rates of small abdominal aortic aneurysms. (J Vasc Surg 1998;27:354-61.

The pseudogap state in superconductors: Extended Hartree approach to time-dependent Ginzburg-Landau Theory

It is well known that conventional pairing fluctuation theory at the Hartree level leads to a normal state pseudogap in the fermionic spectrum. Our goal is to extend this Hartree approximated scheme to arrive at a generalized mean field theory of pseudogapped superconductors for all temperatures $T$. While an equivalent approach to the pseudogap has been derived elsewhere using a more formal Green's function decoupling scheme, in this paper we re-interpret this mean field theory and BCS theory as well, and demonstrate how they naturally relate to ideal Bose gas condensation. Here we recast the Hartree approximated Ginzburg-Landau self consistent equations in a T-matrix form. This recasting makes it possible to consider arbitrarily strong attractive coupling, where bosonic degrees of freedom appear at $T^*$ considerably above $T_c$. The implications for transport both above and below $T_c$ are discussed. Below $T_c$ we find two types of contributions. Those associated with fermionic excitations have the usual BCS functional form. That they depend on the magnitude of the excitation gap, nevertheless, leads to rather atypical transport properties in the strong coupling limit, where this gap (as distinct from the order parameter) is virtually $T$-independent. In addition, there are bosonic terms arising from non-condensed pairs whose transport properties are shown here to be reasonably well described by an effective time-dependent Ginzburg-Landau theory.Comment: 14 pages, 5 figures, REVTeX4, submitted to PRB; clarification of the diagrammatic technique added, one figure update

Understanding the models of community hospital rehabilitation activity (MoCHA): a mixed method study

Introduction To understand the variation in performance between community hospitals, our objectives are: to measure the relative performance (cost efficiency) of rehabilitation services in community hospitals; to identify the characteristics of community hospital rehabilitation that optimise performance; to investigate the current impact of community hospital in-patient rehabilitation for older people on secondary care and the potential impact if community hospital rehabilitation was optimised to best practice nationally; to examine the relationship between the configuration of intermediate care and secondary care bed use; and to develop toolkits for commissioners and community hospital providers to optimise performance. Methods and analysis Four linked studies will be performed. Study 1: Cost efficiency modelling will apply econometric techniques to datasets from the NHS Benchmarking Network surveys of community hospital and intermediate care. This will identify community hospitals’ performance and estimate the gap between high and low performers. Analyses will determine the potential impact if the performance of all community hospitals nationally was optimised to best performance, and examine the association between community hospital configuration and secondary care bed use. Study 2: A national community hospital survey gathering detailed cost data and efficiency variables will be performed. Study 3: In-depth case studies of three community hospitals, two high and one low performing, will be undertaken. Case studies will gather routine hospital and local health economy data. Ward culture will be surveyed. Content and delivery of treatment will be observed. Patients and staff will be interviewed. Study 4: Co-designed web-based quality improvement toolkits for commissioners and providers will be developed, including indicators of performance and the gap between local and best community hospitals performance. Ethics and dissemination Publications will be in peer reviewed journals, reports will be distributed through stakeholder organisations. Ethical approval was obtained from the Bradford Research Ethics committee (reference: 15/YH/0062)

The global carbon budget 1959-2011

Accurate assessments of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the climate policy process, and project future climate change. Present-day analysis requires the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. Here we describe datasets and a methodology developed by the global carbon cycle science community to quantify all major components of the global carbon budget, including their uncertainties. We discuss changes compared to previous estimates, consistency within and among components, and methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. Finally, the global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms. For the last decade available (2002–2011), EFF was 8.3 &pm; 0.4 PgC yr−1, ELUC 1.0 &pm; 0.5 PgC yr−1, GATM 4.3 &pm; 0.1PgC yr−1, SOCEAN 2.5 &pm; 0.5 PgC yr−1, and SLAND 2.6 &pm; 0.8 PgC yr−1. For year 2011 alone, EFF was 9.5 &pm; 0.5 PgC yr−1, 3.0 percent above 2010, reflecting a continued trend in these emissions; ELUC was 0.9 &pm; 0.5 PgC yr−1, approximately constant throughout the decade; GATM was 3.6 &pm; 0.2 PgC yr−1, SOCEAN was 2.7 &pm; 0.5 PgC yr−1, and SLAND was 4.1 &pm; 0.9 PgC yr−1. GATM was low in 2011 compared to the 2002–2011 average because of a high uptake by the land probably in response to natural climate variability associated to La Niña conditions in the Pacific Ocean. The global atmospheric CO2 concentration reached 391.31 &pm; 0.13 ppm at the end of year 2011. We estimate that EFF will have increased by 2.6% (1.9–3.5%) in 2012 based on projections of gross world product and recent changes in the carbon intensity of the economy. All uncertainties are reported as &pm;1 sigma (68% confidence assuming Gaussian error distributions that the real value lies within the given interval), reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. This paper is intended to provide a baseline to keep track of annual carbon budgets in the future

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

The defect in the AT-like hamster cell mutants is complemented by mouse chromosome 9 but not by any of the human chromosomes

X-ray-sensitive Chinese hamster V79 cells mutants, V-C4, V-E5 and V-G8, show an abnormal response to X-ray-induced DNA damage. Like ataxia telangiectasia (AT) cells, they display increased cell killing, chromosomal instability and a diminished inhibition of DNA synthesis following ionizing radiation. To localize the defective hamster gene (XRCC8) on the human genome, human chromosomes were introduced into the AT-like hamster mutants, by microcell mediated chromosome transfer. Although, none of the human chromosomes corrected the defect in these mutants, the defect was corrected by a single mouse chromosome, derived from the A9 microcell donor cell line. In four independent X-ray-resistant microcell hybrid clones of V-E5, the presence of the mouse chromosome was determined by fluorescent in situ hybridization, using a mouse cot-1 probe. By PCR analysis with primers specific for different mouse chromosomes and Southern blot analysis with the mouse Ldlr probe, the mouse chromosome 9, was identified in all four X-ray-resistant hybrid clones. Segregation of the mouse chromosome 9 from these hamster-mouse microcell hybrids led to the loss of the regained X-ray-resistance, confirming that mouse chromosome 9 is responsible for complementation of the defect in V-E5 cells. The assignment of the mouse homolog of the ATM gene to mouse chromosome 9, and the presence of this mouse chromosome only in the radioresistant hamster cell hybrids suggest that the hamster AT-like mutants are homologous to AT, although they are not complemented by human chromosome 11

Low-energy structure of the even-A 96−104 Ru isotopes via g-factor measurements

The transient-field-perturbed angular correlation technique was used with Coulomb excitation in inverse kinematics to perform a systematic measurement of the g factors of the first excited 21+ states in the stable even-A isotopes Ru96-104. The measurements have been made relative to one another under matched kinematic conditions and include a measurement of g(21+)=+0.47(3) in Ru96

Taking the steps toward sustainable livestock: our multidisciplinary global farm platform journey

International audienc

Key traits for ruminant livestock across diverse production systems in the context of climate change: perspectives from a global platform of research farms

Ruminant livestock are raised under diverse cultural and environmental production systems around the globe. Ruminant livestock can play a critical role in food security by supplying high-quality, nutrient-dense food with little or no competition for arable land while simultaneously improving soil health through vital returns of organic matter. However, in the context of climate change and limited land resources, the role of ruminant-based systems is uncertain because of their reputed low efficiency of feed conversion (kilogram of feed required per kilogram of product) and the production of methane as a by-product of enteric fermentation. A growing human population will demand more animal protein, which will put greater pressure on the Earth’s planetary boundaries and contribute further to climate change. Therefore, livestock production globally faces the dual challenges of mitigating emissions and adapting to a changing climate. This requires research-led animal and plant breeding and feeding strategies to optimise ruminant systems. This study collated information from a global network of research farms reflecting a variety of ruminant production systems in diverse regions of the globe. Using this information, key changes in the genetic and nutritional approaches relevant to each system were drawn that, if implemented, would help shape more sustainable future ruminant livestock systems