Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10

Background: The peptide apelin is expressed in human healthy livers and is implicated in the development of hepatic fibrosis and cirrhosis. Mutations in the bone morphogenetic protein receptor type II (BMPR-II) result in reduced plasma levels of apelin in patients with heritable pulmonary arterial hypertension. Ligands for BMPR-II include bone morphogenetic protein 9 (BMP9), highly expressed in liver, and BMP10, expressed in heart and to a lesser extent liver. However, it is not known whether reductions in BMP9 and/or BMP10, with associated reduction in BMPR-II signalling, correlate with altered levels of apelin in patients with liver fibrosis and cirrhosis. Methods: Plasma from patients with liver fibrosis (n = 14), cirrhosis (n = 56), and healthy controls (n = 25) was solid-phase extracted using a method optimised for recovery of apelin, which was measured by ELISA. Results: Plasma apelin was significantly reduced in liver fibrosis (8.3 ± 1.2 pg/ml) and cirrhosis (6.5 ± 0.6 pg/ml) patients compared with controls (15.4 ± 2.0 pg/ml). There was no obvious relationship between apelin and BMP 9 or BMP10 previously measured in these patients. Within the cirrhotic group, there was no significant correlation between apelin levels and disease severity scores, age, sex, or treatment with β-blockers. Conclusions: Apelin was significantly reduced in plasma of patients with both early (fibrosis) and late-stage (cirrhosis) liver disease. Fibrosis is more easily reversible and may represent a potential target for new therapeutic interventions. However, it remains unclear whether apelin signalling is detrimental in liver disease or is beneficial and therefore, whether an apelin antagonist or agonist have clinical use

Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment

17α -ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent. Ozone and activated carbon provide effective wastewater treatments, but their energy intensities and capital/operating costs are formidable barriers to adoption. Here we describe the technical and environmental performance of a fast- developing contender for mitigation of EE2 contamination of wastewater based upon smallmolecule, full-functional peroxidase enzyme replicas called “TAML activators”. From neutral to basic pH, TAML activators with H2O2 efficiently degrade EE2 in pure lab water, municipal effluents and EE2-spiked synthetic urine. TAML/H2O2 treatment curtails estrogenicity in vitro and substantially diminishes fish feminization in vivo. Our results provide a starting point for a future process in which tens of thousands of tonnes of wastewater could be treated per kilogram of catalyst. We suggest TAML/H2O2 is a worthy candidate for exploration as an environmentally compatible, versatile, method for removing EE2 and other pharmaceuticals from municipal wastewaters.Heinz Endowments, the Swiss National Science Foundation, the Steinbrenner Institute for a Steinbrenner Doctoral Fellowship. NMR instrumentation at CMU was partially supported by NSF (CHE-0130903 and CHE-1039870)

Socio-demographic, behavioural and cognitive correlates of work-related sitting time in German men and women

Background: Sitting time is ubiquitous for most adults in developed countries and is most prevalent in three domains: in the workplace, during transport and during leisure time. The correlates of prolonged sitting time in workplace settings are not well understood. Therefore, the aim of this study was to examine the gender-specific associations between the socio-demographic, behavioural and cognitive correlates of work-related sitting time. Methods: A cross-sectional sample of working German adults (n = 1515; 747 men; 43.5 ± 11.0 years) completed questionnaires regarding domain-specific sitting times and physical activity (PA) and answered statements concerning beliefs about sitting. To identify gender-specific correlates of work-related sitting time, we used a series of linear regressions. Results The overall median was 2 hours of work-related sitting time/day. Regression analyses showed for men (β = -.43) and for women (β = -.32) that work-related PA was negatively associated with work-related sitting time, but leisure-related PA was not a significant correlate. For women only, transport-related PA (β = -.07) was a negative correlate of work-related sitting time, suggesting increased sitting times during work with decreased PA in transport. Education and income levels were positively associated, and in women only, age (β = -.14) had a negative correlation with work-related sitting time. For both genders, TV-related sitting time was negatively associated with work-related sitting time. The only association with cognitive correlates was found in men for the belief ‘Sitting for long periods does not matter to me’ (β = .10) expressing a more positive attitude towards sitting with increasing sitting durations. Conclusions: The present findings show that in particular, higher educated men and women as well as young women are high-risk groups to target for reducing prolonged work-related sitting time. In addition, our findings propose considering increasing transport-related PA, especially in women, as well as promoting recreation-related PA in conjunction with efforts to reduce long work-related sitting times

From 'event-led' to 'event-themed' regeneration: the 2002 Commonwealth Games Legacy Programme

Hosting large events has long been associated with the physical regeneration of cities. To supplement these ‘hard’ impacts, cities are now attempting to use events to stimulate ‘softer’ social and economic regeneration. This paper evaluates the impacts of a regeneration Programme adopted in conjunction with the 2002 Commonwealth Games held in Manchester, UK. Alongside its emphasis on social and economic regeneration, this Programme was unusual in that the projects were Games-themed, rather than being directly linked to the event. Despite some concerns about the organisational structures employed and the sustainability of impacts, target beneficiaries have received valuable assistance from the Programme. As such there appears to be valuable lessons that other cities can learn from this example of event regeneration

Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1

Background: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements. The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers. Isothermal amplification methods, such as reversetranscription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices. Methodology/Significant Findings: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water. The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler. The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients. Conclusion: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides

Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling

Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

The contribution of office work to sedentary behaviour associated risk

Background: Sedentary time has been found to be independently associated with poor health and mortality. Further, a greater proportion of the workforce is now employed in low activity occupations such as office work. To date, there is no research that specifically examines the contribution of sedentary work to overall sedentary exposure and thus risk. The purpose of the study was to determine the total exposure and exposure pattern for sedentary time, light activity and moderate/vigorous physical activity (MVPA) of office workers during work and non-work time.Methods: 50 office workers from Perth, Australia wore an Actical (Phillips, Respironics) accelerometer during waking hours for 7 days (in 2008–2009). Participants recorded wear time, waking hours, work hours and daily activities in an activity diary. Time in activity levels (as percentage of wear time) during work and non-work time were analysed using paired t-tests and Pearson’s correlations.Results: Sedentary time accounted for 81.8% of work hours (light activity 15.3% and MVPA 2.9%), which was significantly greater than sedentary time during non-work time (68.9% p 30 minutes) and significantly less brief duration (0–10 minutes) light intensity activity during work hours compared to non-work time (p < 0.001). Further, office workers had fewer breaks in sedentary time during work hours compared to non-work time (p < 0.001).Conclusions: Office work is characterised by sustained sedentary time and contributes significantly to overall sedentary exposure of office workers

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente