The epidemiology of Human Papillomavirus (HPV) infection and epigenetic factors associated with the development of cervical cancer precursor lesions in women living with HIV in Africa.

Background: The relationships between human papillomavirus (HPV) and HIV, in an African context are limited. Given the large number of women living with HIV (WLHIV) accessing antiretroviral therapy (ART), it is important to establish associations of HIV-related factors with high-risk (HR)-HPV and cervical intraepithelial neoplasia (CIN). Design: Prospective cohort of WLHIV attending HIV treatment centres in Ouagadougou, Burkina Faso (BF) and Johannesburg, South Africa (SA). Methods: At baseline and endline (median 16 months), cervical samples and biopsies were analyzed for HPV genotyping (InnoLiPA) and by histology. HPV serology targeting 15 HPV types (12 HR) was by multiplexed pseudovirion-based serological assay. Methylation of a human gene EPB41L3 and HPV16 was measured by pyrosequencing. Logistic regression was used to estimate associations of HIV-related factors with HR-HPV and CIN2+ outcomes. Results: Among 1238 enrolled WLHIV (BF=615; SA=623) HR-HPV prevalence was 59.1% in BF and 79.1% in SA. CIN2+ prevalence was 5.8% in BF and 22.5% in SA. Prolonged ART use (>2 years) was associated with lower HR-HPV prevalence in BF and lower CIN2+ prevalence compared to short-duration ART users and ART-naïve participants in SA. Among 963 (77.8%) women seen at endline, HR-HPV persistence was 41.1% in BF and 30.2% in SA; CIN2+ incidence over 16-months was 1.2% in BF and 5.8% in SA. HR-HPV persistence was lower among those with prolonged ART compared to ART-naïve and short-duration ART users. CIN2+ incidence was reduced among women on ART in SA. HPV seroprevalence and seropersistence were high (93% and 95%, respectively). Seroconversion was 23.1%, and was higher among recent ART users (≤2 years) and among those with type-specific DNA persistence compared to those who cleared infection. v The human gene EPB41L3 showed elevated methylation in CIN2+ compared to ≤CIN1 (Mann Whitney U p=<0.001) at baseline. Higher methylation levels were found among recent ART users (≤2 years) and women with CD4 ≤200 cells/mm3. Conclusion: WLHIV in BF and SA have high rates of HR-HPV and CIN2+, and WLHIV in SA have higher CIN2+, linked with poorer control of HIV and higher frequency of cofactors for HR-HPV and CIN2+. Prolonged and effective ART is important in controlling HR-HPV and the development of CIN2+. WLHIV are infected with multiple HR-HPV types and there is limited evidence that HPV antibodies protect against same-type reinfection. WLHIV may benefit from vaccination using a multivalent vaccine. DNA methylation of a tumour suppressor gene EPB41L3 is elevated among women with CIN2+ and shows promise as a biomarker test for CIN2+ prediction among WLHIV

Returns to Education and the Demand for Labour in Vietnam. ESRI WP506. July 2015

Using data from the Vietnam Household Living Standards Survey, this paper examines the returns to education in Vietnam in 2002 and 2010, and how these returns changed over time. Given the economic growth that took place during this time period, the relative demand for labour is also assessed in order to identify if skill-biased technical change played a role in explaining the returns to education in Vietnam at a time of exceptional economic growth. The male and female education returns displayed a linear pattern in both 2002 and 2010, with earnings rising with increased levels of education. Relative to males with no qualifications, the returns to those with a vocational training qualification or below fell between 2002 and 2010, while the economic returns to a college education and above increased. Similar results were observed for females. In relation to relative labour demand, the results indicated that the demand for all levels of education (apart from males with a high school qualification) relative to those with no qualifications grew between 2002 and 2010. However, there was particularly strong growth in the demand for those with a vocational training qualification and above, especially an advanced degree qualification. Findings from the paper show that high levels of economic growth in Vietnam between 2002 and 2010 have facilitated increasing returns to education and demand for high skilled labour. In addition, there appears to be shortages for some types of skilled labour

Data reduction for the MIPS far-infrared arrays

Traditional photoconductive detectors are used at 70 and 160 microns in the Multiband Imaging Photometer for SIRTF. These devices are highly sensitivity to cosmic rays and have complex response characteristics, all of which must be anticipated in the data reduction pipeline. The pipeline is being developed by a team at the SIRTF Science Center, where the detailed design and coding are carried out, and at Steward Observatory, where the high level algorithms are developed and detector tests are conducted to provide data for pipeline experiments. A number of innovations have been introduced. Burger's model is used to extrapolate to asymptotic values for the response of the detectors. This approach permits rapid fitting of the complexities in the detector response. Examples of successful and unsuccessful fits to the laboratory test data are shown

Evolving robotic surgery training and improving patient safety, with the integration of novel technologies

INTRODUCTION: Robot-assisted surgery is becoming increasingly adopted by multiple surgical specialties. There is evidence of inherent risks of utilising new technologies that are unfamiliar early in the learning curve. The development of standardised and validated training programmes is crucial to deliver safe introduction. In this review, we aim to evaluate the current evidence and opportunities to integrate novel technologies into modern digitalised robotic training curricula. METHODS: A systematic literature review of the current evidence for novel technologies in surgical training was conducted online and relevant publications and information were identified. Evaluation was made on how these technologies could further enable digitalisation of training. RESULTS: Overall, the quality of available studies was found to be low with current available evidence consisting largely of expert opinion, consensus statements and small qualitative studies. The review identified that there are several novel technologies already being utilised in robotic surgery training. There is also a trend towards standardised validated robotic training curricula. Currently, the majority of the validated curricula do not incorporate novel technologies and training is delivered with more traditional methods that includes centralisation of training services with wet laboratories that have access to cadavers and dedicated training robots. CONCLUSIONS: Improvements to training standards and understanding performance data have good potential to significantly lower complications in patients. Digitalisation automates data collection and brings data together for analysis. Machine learning has potential to develop automated performance feedback for trainees. Digitalised training aims to build on the current gold standards and to further improve the 'continuum of training' by integrating PBP training, 3D-printed models, telementoring, telemetry and machine learning

Translation, cultural adaptation and field-testing of the Thinking Healthy Program for Vietnam

Background: Depression and anxiety are prevalent among women in low- and lower-middle income countries who are pregnant or have recently given birth. There is promising evidence that culturally-adapted, evidence-informed, perinatal psycho-educational programs implemented in local communities are effective in reducing mental health problems. The Thinking Healthy Program (THP) has proved effective in Pakistan. The aims were to adapt the THP for rural Vietnam; establish the program’s comprehensibility, acceptability and salience for universal use, and investigate whether administration to small groups of women might be of equivalent effectiveness to administration in home visits to individual women. Methods: The THP Handbook and Calendar were made available in English by the program developers and translated into Vietnamese. Cultural adaptation and field-testing were undertaken using WHO guidance. Field-testing of the four sessions of THP Module One was undertaken in weekly sessions with a small group in a rural commune and evaluated using baseline, process and endline surveys. Results: The adapted Vietnamese version of the Thinking Healthy Program (THP-V) was found to be understandable, meaningful and relevant to pregnant women, and commune health centre and Women’s Union representatives in a rural district. It was delivered effectively by trained local facilitators. Role-play, brainstorming and small-group discussions to find shared solutions to common problems were appraised as helpful learning opportunities. Conclusions: The THP-V is safe and comprehensible, acceptable and salient to pregnant women without mental health problems in rural Vietnam. Delivery in facilitated small groups provided valued opportunities for role-play rehearsal and shared problem solving. Local observers found the content and approach highly relevant to local needs and endorsed the approach as a mental health promotion strategy with potential for integration into local universal maternal and child health services. These preliminary data indicate that the impact of the THP-V should be tested in its complete form in a large scale trial

Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation.

BACKGROUND: We report striking and unanticipated improvements in maladaptive behaviours in Prader-Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild-moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. METHODS: Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. RESULTS: Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. CONCLUSIONS: We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.This study was funded by The Dunhill Medical Trust, Addenbrooke’s Charitable Trust, Isaac Newton Trust , and Prader-Willi Association UK. Funding bodies had no role in study design, data collection, data analysis, data interpretation, writing of the report or the decision to submit for publication. We are grateful to the NIHR Collaborations for Leadership in Applied Health Care Research and Care (CLAHRC) East of England for financial support to AJH and HAR and to the Health Foundation for support of AJH. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final version of the article. It first appeared from Taylor & Francis via http://dx.doi.org/10.1111/jir.1220

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

Correctly validating results from single molecule data: the case of stretched exponential decay in the catalytic activity of single lipase B molecules

The question of how to validate and interpret correctly the waiting time probability density functions (WT-PDFs) from single molecule data is addressed. It is shown by simulation that when a stretched exponential WT-PDF, with a stretched exponent alfa and a time scale parameter tau, generates the off periods of a two-state trajectory, a reliable recovery of the input WT-PDF from the trajectory is obtained even when the bin size used to define the trajectory, dt, is much larger than the parameter tau. This holds true as long as the first moment of the WT-PDF is much larger than dt. Our results validate the results in an earlier study of the activity of single Lipase B molecules and disprove recent related critique

Decreasing intensity of open-ocean convection in the Greenland and Iceland seas

The air–sea transfer of heat and fresh water plays a critical role in the global climate system. This is particularly true for the Greenland and Iceland seas, where these fluxes drive ocean convection that contributes to Denmark Strait overflow water, the densest component of the lower limb of the Atlantic Meridional Overturning Circulation (AMOC). Here we show that the wintertime retreat of sea ice in the region, combined with different rates of warming for the atmosphere and sea surface of the Greenland and Iceland seas, has resulted in statistically significant reductions of approximately 20% in the magnitude of the winter air–sea heat fluxes since 1979. We also show that modes of climate variability other than the North Atlantic Oscillation (NAO) are required to fully characterize the regional air–sea interaction. Mixed-layer model simulations imply that further decreases in atmospheric forcing will exceed a threshold for the Greenland Sea whereby convection will become depth limited, reducing the ventilation of mid-depth waters in the Nordic seas. In the Iceland Sea, further reductions have the potential to decrease the supply of the densest overflow waters to the AMOC

The regional economic impact of more graduates in the labour market: a “micro-to-macro” analysis for Scotland

This paper explores the system-wide impact of graduates on the regional economy. Graduates enjoy a significant wage premium, often interpreted as reflecting their greater productivity relative to non-graduates. If this is so there is a clear and direct supply-side impact of HEI activities on regional economies. We use an HEI-disaggregated computable general equilibrium model of Scotland to estimate the impact of the growing proportion of graduates in the Scottish labour force that is implied by the current participation rate and demographic change, taking the graduate wage premium in Scotland as an indicator of productivity enhancement. While the detailed results vary with alternative assumptions about the extent to which wage premia reflect productivity, they do suggest that the long-term supply-side impacts of HEIs provide a significant boost to regional GDP. Furthermore, the results suggest that the supply-side impacts of HEIs are likely to be more important than the expenditure impacts that are the focus of most HEI impact studies