Research reports on the diagnosis and detection; environment and infection; and evaluation of interventions on infectious diseases.

published_or_final_versio

Cancer event rate and mortality with thienopyridines: a systematic review and meta-analysis

Introduction Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment. A recent concern has come to light regarding the safety of thienopyridines because of the possible risk of malignancy. We therefore performed a systematic review and meta-analysis to evaluate the association between thienopyridine exposure and malignancy. Methods We searched the MEDLINE and EMBASE databases in March 2016 for studies that evaluated incident cancer and cancer mortality with and without exposure to thienopyridines. Relevant studies were identified, and data were extracted and analysed using random-effects meta-analysis. Results A total of nine studies (six randomised controlled trials and three cohort studies) that included 282,084 participants were included. The cancer event rate with clopidogrel and prasugrel was 3.25% and 1.58% respectively. When compared with standard aspirin or placebo, thienopyridines are not significantly associated with cancer mortality and event rate (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.80–1.56, n = 3; and OR 0.92, 95% CI 0.52–1.64, n = 2, respectively. Further analyses examining clopidogrel showed no significant association with cancer event rate or malignancy-related death. When comparing prasugrel with clopidogrel, no significant association was noted for cancer event rate (OR 1.10, 95% CI 0.89–1.37, n = 2]. Subanalyses according to cancer location showed that thienopyridines are not significantly associated with malignancy mortality and/or incidence. Conclusions Our results suggest that there is currently insufficient evidence to suggest that thienopyridine exposure is associated with an increased risk of cancer event rate or mortality

Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction

Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity

Dissolution dominating calcification process in polar pteropods close to the point of aragonite undersaturation

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Omega_Ar). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Omega_Ar,0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Var levels slightly above 1 and lower at Omega_Ar levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Var derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Omega_Ar levels close to 1, with net shell growth ceasing at an Omega_Ar of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean

Niche inheritance: a cooperative pathway to enhance cancer cell fitness though ecosystem engineering

Cancer cells can be described as an invasive species that is able to establish itself in a new environment. The concept of niche construction can be utilized to describe the process by which cancer cells terraform their environment, thereby engineering an ecosystem that promotes the genetic fitness of the species. Ecological dispersion theory can then be utilized to describe and model the steps and barriers involved in a successful diaspora as the cancer cells leave the original host organ and migrate to new host organs to successfully establish a new metastatic community. These ecological concepts can be further utilized to define new diagnostic and therapeutic areas for lethal cancers.Comment: 8 pages, 1 Table, 4 Figure

Stability analysis of electrical powered wheelchair-mounted robotic-assisted transfer device

The ability of people with disabilities to live in their homes and communities with maximal independence often hinges, at least in part, on their ability to transfer or be transferred by an assistant. Because of limited resources and the expense of personal care, robotic transfer assistance devices will likely be in great demand. An easy-to-use system for assisting with transfers, attachable to electrical powered wheelchairs (EPWs) and readily transportable, could have a significant positive effect on the quality of life of people with disabilities. We investigated the stability of our newly developed Strong Arm, which is attached and integrated with an EPW to assist with transfers. The stability of the system was analyzed and verified by experiments applying different loads and using different system configurations. The model predicted the distributions of the system’s center of mass very well compared with the experimental results. When real transfers were conducted with 50 and 75 kg loads and an 83.25 kg dummy, the current Strong Arm could transfer all weights safely without tip-over. Our modeling accurately predicts the stability of the system and is suitable for developing better control algorithms to enhance the safety of the device

Enriching the hot circumgalactic medium

Simple models of galaxy formation in a cold darkmatter universe predict that massive galaxies are surrounded by a hot, quasi-hydrostatic circumgalactic corona of slowly cooling gas, predominantly accreted from the intergalactic medium (IGM). This prediction is borne out by the recent cosmological hydrodynamical simulations of Crain et al., which reproduce observed scaling relations between the X-ray and optical properties of nearby disc galaxies. Such coronae are metal poor, but observations of the X-ray emitting circumgalactic medium (CGM) of local galaxies typically indicate enrichment to near-solar iron abundance, potentially signalling a shortcoming in current models of galaxy formation.We show here that, while the hotCGMof galaxies formed in the simulations is typically metal poor in a mass-weighted sense, its X-ray luminosity-weighted metallicity is often close to solar. This bias arises because the soft X-ray emissivity of a typical ∼0.1 keV corona is dominated by collisionally excited metal ions that are synthesized in stars and recycled into the hot CGM. We find that these metals are ejected primarily by stars that form in situ to the main progenitor of the galaxy, rather than in satellites or external galaxies. The enrichment of the hot CGM therefore proceeds in an ‘inside–out’ fashion throughout the assembly of the galaxy: metals are transported from the central galaxy by supernova-driven winds and convection over several Gyr, establishing a strong negative radial metallicity gradient. Whilst metal ions synthesized by stars are necessary to produce the X-ray emissivity that enables the hot CGM of isolated galaxies to be detected with current instrumentation, the electrons that collisionally excite them are equally important. Since our simulations indicate that the electron density of hot coronae is dominated by the metal-poor gas accreted from the IGM, we infer that the hot CGM observed via X-ray emission is the outcome of both hierarchical accretion and stellar recycling

Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study

BACKGROUND: Inflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse population of HIV-infected and uninfected adults. METHODS: Prospective and retrospective clinical and laboratory data were collected on TB patients seen between January 1999-December 2008 at four UK centres selected to represent a wide ethnic and socio-economic mix of TB patients. Data on ethnicity and HIV status were obtained for all individuals. The associations between other potential risk factors and PR were assessed in a nested case-control study. All PR cases were matched two-to-one to controls by calendar time and centre. RESULTS: Of 1817 TB patients, 82 (4.5 %, 95 % CI 3.6-5.5 %) were identified as having a PR event. The frequency of PR was 14.4 % (18/125; 95 % CI 8.2-20.6 %) and 3.8 % (64/1692; 2.9-4.7) for HIV-positive and HIV-negative individuals respectively. There were no differences observed in PR frequency according to ethnicity, although the site was more likely to be pulmonary in those of black and white ethnicity, and lymph node disease in those of Asian ethnicity. In multivariate analysis of the case-control cohort, HIV-positive patients had five times the odds of developing PR (aOR = 5.05; 95 % CI 1.28-19.85, p = 0.028), whilst other immunosuppression e.g. diabetes, significantly reduced the odds of PR (aOR = 0.01; 0.00-0.27, p = 0.002). Patients with positive TB culture had higher odds of developing PR (aOR = 6.87; 1.31-36.04, p = 0.045) compared to those with a negative culture or those in whom no material was sent for culture. Peripheral lymph node disease increased the odds of a PR over 60-fold 4(9.60-431.25, p < 0.001). CONCLUSION: HIV was strongly associated with PR. The increased potential for PR in people with culture positive TB suggests that host mycobacterial burden might be relevant. The increased risk with TB lymphadenitis may in part arise from the visibility of clinical signs at this site. Non-HIV immunosuppression may have a protective effect. This study highlights the difficulties in predicting PR using routinely available demographic details, clinical symptoms or biochemical markers

Portuguese validation of the Bergen Facebook Addiction Scale: an Empirical Study

Previous research on Social Networking Sites (SNSs) addiction have suggest the need to improve assessment of this behavioral addiction. The present study aimed at validating a Portuguese version of the Bergen Facebook Addiction Scale (BFAS), a widely used instrument to assess addiction to Facebook. A study was conducted in a sample of 509 Portuguese adolescent using an online survey. The psychometric properties (construct validity, criterion validity, and reliability) of the Portuguese BFAS was scrutinized. The results from the psychometric analyses suggested that the new validated instrument had excellent psychometric properties. The CFA confirmed the original one-factor solution of the BFAS and criterion validity was warranted. The reliability of the BFAS was supported by satisfactory levels of internal consistency as measured by the Cronbach’s alpha (α = .83), composite reliability (CR = .82), and factor determinacy (FD = .91). Overall, the results provided empirical support for the validity and reliability of the Portuguese BFAS. Moreover, the results were highly comparable with the findings of the original development study of the BFAS and cross-cultural support for the scale was obtained

The new very small angle neutron scattering spectrometer at Laboratoire Leon Brillouin

The design and characteristics of the new very small angle neutron scattering spectrometer under construction at the Laboratoire Leon Brillouin is described. Its goal is to extend the range of scattering vectors magnitudes towards 2x10{-4} /A. The unique feature of this new spectrometer is a high resolution two dimensional image plate detector sensitive to neutrons. The wavelength selection is achieved by a double reflection supermirror monochromator and the collimator uses a novel multibeam design