A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection

Training peers to treat Ebola centre workers with anxiety and depression in Sierra Leone

Background: Following the 2014 Ebola virus disease (EVD) outbreak in West Africa, the UK Department for International Development funded South London and Maudsley National Health Service (NHS) to develop a psychological intervention that ex-Ebola Treatment Centre (ETC) staff could be trained to deliver to their peers to improve mental health in Sierra Leone. / Aim: The two key aims were to assess the feasibility of training a national team to deliver a cognitive behavioural therapy (CBT)–based group intervention, and to evaluate the effectiveness of the overall intervention within this population. / Methods: UK clinicians travelled to Sierra Leone to train a small team of ex-ETC staff in a three-phased CBT-based intervention. Standardised clinical measures, as well as bespoke measures, were applied with participants through the intervention to assess changes in mental health symptomology, and the effectiveness of the intervention. / Results: The results found improvements across all factors of mental health in the bespoke measure from phase 1 to phase 3. Additionally, the majority of standardised clinical measures showed improvements between phase 2 and the start of phase 3, and pre- and post-phase 3. / Conclusion: Overall, the findings suggest that it is possible to train staff from ETCs to deliver effective CBT interventions to peers. The implications of these results are discussed, including suggestions for future research and clinical intervention implementation within this population. The limitations of this research are also addressed

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

Radiographs and low field MRI (0.2T) as predictors of efficacy in a weight loss trial in obese women with knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>To study the predictive value of baseline radiographs and low-field (0.2T) MRI scans for the symptomatic outcome of clinically significant weight loss in obese patients with knee osteoarthritis.</p> <p>Methods</p> <p>In this study we hypothesize that imaging variables assessed with radiographs and MRI scans pre-treatment can predict the symptomatic changes following a recommended clinically significant weight reduction Patients were recruited from the Department of Rheumatology, Frederiksberg Hospital, Denmark. Eligibility criteria were: age >18 years; primary osteoarthritis according to ACR; BMI > 28 kg/m2; motivation for weight loss. Subjects were randomly assigned to either intervention by low-energy diet (LED) for 8 weeks followed by another 24 weeks of dietary instruction or control-group. MRI scans and radiographs were scored for structural changes and these parameters were examined as independent predictors of changes in osteoarthritis symptoms after 32 weeks. The outcome assessor and statistician were blinded to group allocation.</p> <p>Results</p> <p>No significant correlations were found between imaging variables and changes in Western Ontario and McMaster Universities Index of Osteoarthritis (Spearman's test, r < 0.33 and P > 0.07).</p> <p>Only the LED group achieved a weight loss, with a mean difference of 16.3 kg (95%CI: 13.4-19.2;P < 0.0001) compared to the control group. The total WOMAC index showed a significant difference favouring LED, with a group mean difference of - 321.3 mm (95%CI: -577.5 to -65.1 mm; P = 0.01). No significant adverse events were reported.</p> <p>Conclusion</p> <p>Stage of joint destruction, assessed on either radiographs or low-field MRI (0.2T), does not preclude a symptoms relief following a clinically relevant weight loss in elderly obese female patients with knee osteoarthritis.</p

CO(1-0) in z gtrsim 4 Quasar Host Galaxies: No Evidence for Extended Molecular Gas Reservoirs

We present 12CO(J = 1 → 0) observations of the high-redshift quasi-stellar objects (QSOs) BR 1202-0725 (z = 4.69), PSS J2322+1944 (z = 4.12), and APM 08279+5255 (z = 3.91) using the NRAO Green Bank Telescope (GBT) and the MPIfR Effelsberg 100 m telescope. We detect, for the first time, the CO ground-level transition in BR 1202-0725. For PSS J2322+1944 and APM 08279+5255, our observations result in line fluxes that are consistent with previous NRAO Very Large Array (VLA) observations, but they reveal the full line profiles. We report a typical lensing-corrected velocity-integrated intrinsic 12CO(J = 1 → 0) line luminosity of L = 5 × 1010 K km s-1 pc2 and a typical total H2 mass of M(H2) = 4 × 1010 M for the sources in our sample. The CO/FIR luminosity ratios of these high-z sources follow the same trend as seen for low-z galaxies, leading to a combined solution of log LFIR = (1.39 ± 0.05) log LCO - 1.76. It has previously been suggested that the molecular gas reservoirs in some quasar host galaxies may exhibit luminous, extended 12 CO(J = 1 → 0) components that are not observed in the higher J CO transitions. Using the line profiles and the total intensities of our observations and large velocity gradient (LVG) models based on previous results for higher J CO transitions, we derive that emission from all CO transitions is described well by a single gas component in which all molecular gas is concentrated in a compact nuclear region. Thus, our observations and models show no indication of a luminous extended, low surface brightness molecular gas component in any of the high-redshift QSOs in our sample. If such extended components exist, their contribution to the overall luminosity is limited to at most 30%

G11.92-0.61 MM1: A Keplerian disc around a massive young proto-O star

The formation process of massive stars is not well understood, and advancement in our understanding benefits from high resolution observations and modelling of the gas and dust surrounding individual high-mass (proto)stars. Here we report sub-arcsecond (<1550 au) resolution observations of the young massive star G11.92-0.61 MM1 with the SMA and VLA. Our 1.3 mm SMA observations reveal consistent velocity gradients in compact molecular line emission from species such as CH$_3$CN, CH$_3$OH, OCS, HNCO, H$_2$CO, DCN and CH$_3$CH$_2$CN, oriented perpendicular to the previously reported bipolar molecular outflow from MM1. Modelling of the compact gas kinematics suggests a structure undergoing rotation around the peak of the dust continuum emission. The rotational profile can be well fit by a model of a Keplerian disc, including infall, surrounding an enclosed mass of 30-60M$_{\odot}$, of which 2-3M$_{\odot}$ is attributed to the disc. From modelling the CH$_3$CN emission, we determine that two temperature components, of 150 K and 230 K, are required to adequately reproduce the spectra. Our 0.9 and 3.0cm VLA continuum data exhibit an excess above the level expected from dust emission; the full centimetre-submillimetre wavelength spectral energy distribution of MM1 is well reproduced by a model including dust emission, an unresolved hypercompact H{\i}{\i} region, and a compact ionised jet. In combination, our results suggest that MM1 is an example of a massive proto-O star forming via disc accretion, in a similar way to that of lower mass stars.European Research Council (ERC-2013-ADG DISCSIM project (Grant ID: 341137), ERC-2011-ADG ECOGAL project (Grant ID: 291227)), Science and Technology Facilities Council (Grant ID: ST/M001296/1), Royal Astronomical Society (Undergraduate Research Bursary)This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw191

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

ALMA observations of the Extended Green Object G19.01−0.03 – I. A Keplerian disc in a massive protostellar system

Using the Atacama Large Millimetre/submillimeter Array (ALMA) and the Karl G. Jansky Very Large Array (VLA), we observed the Extended Green Object (EGO) G19.01-0.03 with sub-arcsec resolution from 1.05 mm to 5.01 cm wavelengths. Our 0.4 arcsec 1600 au angular resolution ALMA observations reveal a velocity gradient across the millimetre core MM1, oriented perpendicular to the previously known bipolar molecular outflow, which is consistently traced by 20 lines of 8 molecular species with a range of excitation temperatures, including complex organic molecules (COMs). Kinematic modelling shows the data are well described by models that include a disc in Keplerian rotation and infall, with an enclosed mass of 40-70 M (within a 2000 au outer radius) for a disc inclination angle of i = 40, of which 5.4-7.2 M is attributed to the disc. Our new VLA observations show that the 6.7 GHz Class II methanol masers associated with MM1 fo a partial ellipse, consistent with an inclined ring, with a velocity gradient consistent with that of the theal gas. The disc-to-star mass ratio suggests the disc is likely to be unstable and may be fragmenting into as-yet-undetected low-mass stellar companions. Modelling the centimetre-millimetre spectral energy distribution of MM1 shows the ALMA 1.05 mm continuum emission is dominated by dust, whilst a free-free component, interpreted as a hypercompact H ii region, is required to explain the VLA 5 cm emission. The high enclosed mass derived for a source with a moderate bolometric luminosity (104L) suggests that the MM1 disc may feed an unresolved high-mass binary system

A Neural Network for Stance Phase detection in smart cane users

Slides from conferencePersons with disabilities often rely on assistive devices to carry on their Activities of Daily Living. Deploying sensors on these devices may provide continuous valuable knowledge on their state and condition. Canes are among the most frequently used assistive devices, regularly employed for ambulation by persons with pain on lower limbs and also for balance. Load on canes is reportedly a meaningful condition indicator. Ideally, it corresponds to the time cane users support weight on their lower limb (stance phase). However, in reality, this relationship is not straightforward. We present a Multilayer Perceptron to reliably predict the Stance Phase in cane users using a simple support detection module on commercial canes. The system has been successfully tested on five cane users in care facilities in Spain. It has been optimized to run on a low cost microcontroller.This work has been supported by: Proyectos Puente and programa operativo de empleo juvenil (UMAJI58) and Plan Propio de Investigación at University of Malaga and the Swedish Knowledge Foundation (KKS) through the research profile Embedded Sensor Systems for Health (ESS−H) at Malardalen University, Sweden. Authors would like to ac- knowledge PONIENTE and LOS NARANJOS senior centers for their support during the tests. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec