Initial validation of the arthroscopic skills acquisition tools (ASATs) : a low cost, online tool to develop and evaluate core skills for shoulder arthroscopy

There are increasing time pressures on surgical training, including the European Working Time Directive. Developing arthroscopic surgical skills (keyhole surgery into a joint) has a longer learning curve than open surgery, driving the need to develop efficient training techniques. Virtual reality (VR) simulators offer great potential but such high fidelity simulators are not widespread because of their cost and subsequent access restrictions. A structured program of developing transferrable skills using widely accessible, low cost, but low fidelity simulators may help maximise training opportunities on VR simulators. To address this, the author developed the Arthroscopic Skills Acquisition Tools (ASATs), designed to develop and evaluate the core skills for shoulder arthroscopy, to complement training on VR simulators, cadavers and real patients. This thesis presents the initial validation study of the ASATs. Performance, assessed using a VR simulator correlates with intra-operative and cadaveric arthroscopic performance and can differentiate between novices and experts, thereby providing a practical “gold standard” test environment for the initial validation of the ASATs. This MPhil study aims to evaluate correlations between performance measured using one of the ASATs and performance on a VR shoulder arthroscopy simulator. Following ethical approvals, 49 volunteers were recruited and individually received a 1-hour standardised introduction and familiarisation process containing written material, videos and five different ASATs. They were then assessed using a sixth ASAT and four VR tasks. Correlations were assessed between the ASAT measures and the VR measures using Pearson’s correlation coefficients. The results showed 64 significant correlations from a possible 171, of which 19 showed a moderate or stronger relationship (r > 0.5). More significantly was the correlations pattern, which helps to identify which performance measures to target during further development work on the ASATs. However, there remains questions about the optimal timing, intensity and competence levels of such training

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

A New Vaccine for Tuberculosis: The Challenges of Development and Deployment

Tuberculosis (TB) is one of the world’s leading causes of death due to infection and efforts to control TB would be substantially aided by the availability of an improved TB vaccine. There are currently nine new TB vaccines in clinical development, and the first efficacy trials are due to commence in 2009. There are many complex ethical issues which arise at all stages of TB vaccine development, from the need to conduct trials in developing countries to informed consent and the process of ethical review. While it is important that these issues are discussed, it may also be timely to consider the challenges which may arise if a vaccine in clinical development proves to be highly effective. We examine a number of scenarios where decisions on the deployment of a new TB vaccine may impact on the rights and liberty of the individual

A Close Nuclear Black Hole Pair in the Spiral Galaxy NGC 3393

The current picture of galaxy evolution advocates co-evolution of galaxies and their nuclear massive black holes (MBHs), through accretion and merging. Quasar pairs (6,000-300,000 light-years separation) exemplify the first stages of this gravitational interaction. The final stages, through binary MBHs and final collapse with gravitational wave emission, are consistent with the sub-light-year separation MBHs inferred from optical spectra and light-variability of two quasars. The double active nuclei of few nearby galaxies with disrupted morphology and intense star formation (e.g., NGC 6240 and Mkn 463; ~2,400 and ~12,000 light-years separation respectively) demonstrate the importance of major mergers of equal mass spirals in this evolution, leading to an elliptical galaxy, as in the case of the double radio nucleus (~15 light-years separation) elliptical 0402+379. Minor mergers of galaxies with a smaller companion should be a more common occurrence, evolving into spiral galaxies with active MBH pairs, but have hitherto not been seen. Here we report the presence of two active MBHs, separated by ~430 light-years, in the Seyfert galaxy NGC 3393. The regular spiral morphology and predominantly old circum-nuclear stellar population of this galaxy, and the closeness of the MBHs embedded in the bulge, suggest the result of minor merger evolution.Comment: Preprint (not final) version of a paper to appear in Natur

Broad-band X-ray spectral analysis of the Seyfert 1 galaxy GRS 1734-292

We discuss the broad-band X-ray spectrum of GRS 1734−292 obtained from non-simultaneous XMM–Newton and NuSTAR (Nuclear Spectroscopic Telescope Array) observations, performed in 2009 and 2014, respectively. GRS1734−292 is a Seyfert 1 galaxy, located near the Galactic plane at z = 0.0214. The NuSTAR spectrum (3–80 keV) is dominated by a primary power-law continuum with Γ = 1.65 ± 0.05 and a high-energy cut-off Ec=53+11−8 keV, one of the lowest measured by NuSTAR in a Seyfert galaxy. Comptonization models show a temperature of the coronal plasma of kTe=11.9+1.2−0.9 keV and an optical depth, assuming a slab geometry, τ=2.98+0.16−0.19 or a similar temperature and τ=6.7+0.3−0.4 assuming a spherical geometry. The 2009 XMM–Newton spectrum is well described by a flatter intrinsic continuum (⁠Γ=1.47+0.07−0.03⁠) and one absorption line due to Fe XXV Kα produced by a warm absorber. Both data sets show a modest iron Kα emission line at 6.4 keV and the associated Compton reflection, due to reprocessing from neutral circumnuclear material

Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106

LRRK2 deficiency induced mitochondrial Ca2+ efflux inhibition can be rescued by Na+/Ca2+/Li+ exchanger upregulation

Variants of leucine-rich repeat kinase 2 (lrrk2) are associated with an increased risk in developing Parkinson’s disease (PD). Mitochondrial dysfunction and specifically mitochondrial Ca2+ handling has been linked to the pathogenesis of PD. Here we describe for the second time a mitochondrial Ca2+ efflux deficiency in a model displaying alterations in a PD-associated risk protein. LRRK2 deletion, inhibition and mutations led to an impaired mitochondrial Ca2+ extrusion via Na+/Ca2+/Li+ exchanger (NCLX) which in turn lowered mitochondrial permeability transition pore (PTP) opening threshold and increased cell death. The mitochondrial membrane potential was found not to be the underlying cause for the Ca2+ extrusion deficiency. NCLX activity was rescued by a direct (phosphomimetic NCLX mutant) and indirect (protein kinase A) activation which in turn elevated the PTP opening threshold. Therefore, at least two PD-associated risk protein pathways appear to converge on NCLX controlling mitochondrial Ca2+ extrusion and therefore mitochondrial health. Since mitochondrial Ca2+ overload has been described in many neurological disorders this study warrants further studies into NCLX as a potential therapeutic target

Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.</p> <p>Methods</p> <p>We performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of <it>Mycobacterium tuberculosis </it>bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.</p> <p>Results</p> <p>From 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for <it>M. tuberculosis</it>, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for <it>M. tuberculosis </it>(p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.</p> <p>Conclusions</p> <p>Mycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.</p

Capillary Electrophoresis Separation of Protein Composition of γ-Irradiated Food Pathogens Listeria monocytogenes and Staphylococcus aureus

which were previously treated at different irradiation doses., one protein (50 S ribosomal protein) with the MW of 16.3 kDa was significantly decreased at a low dose of irradiation treatment and the other protein (transcriptional regulator CtsR) with the MW of 17.7 kDa was increased significantly (P≤0.05) at all doses of irradiation treatment compared to control.. The research further confirmed that capillary electrophoresis is a useful method to separate and analyse proteins expression which may be related to the resistance or sensitivity of food pathogens to γ-irradiation