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Background We developed a COVID-Influenza Combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) and quadrivalent influenza hemagglutinin (HA) protein nanoparticles (qNIV), and Matrix-MTM adjuvant. rS/Matrix-M previously demonstrated efficacy against COVID-19 in Phase 3 trials, while qNIV/Matrix-M previously demonstrated induction of broadly cross-reactive antibodies. Here we report preliminary safety and immunogenicity results of a first-ever Phase 1/2 CIC dose-finding trial. Methods Seropositive (COVID-19 vaccinated ≥ 8 weeks prior) participants (N=642) aged 50-70 years were randomized equally, to receive two intramuscular doses, 56 days apart, to 1 of 14 different dose/formulations of CIC using a design of experiments approach (dose range: rS 2.5-22.5ug, HA 5-60ug; and 50ug Matrix-M), or to 1 of 2 reference formulations of either standalone rS with Matrix-M [2 doses] or qNIV with Matrix-M [1 dose only]. Pre- and post-vaccination (Days 0, 28, 56, 70, 84, 182) immunogenicity assessments including SARS-CoV-2 anti-S IgG and influenza HAI antibodies to vaccine-homologous strains. Reactogenicity was assessed 7 days following each dose, and safety outcomes assessed through Day 70. Multiple regression was used to create predictive models to assess antibody response surfaces and for dose optimization. Results All CIC formulations were well tolerated, with a reactogenicity and safety profile generally comparable to standalone rS or qNIV. Regression modelling of post-first dose responses revealed that both rS and HA antigens in a CIC formulation modestly interfered with each other, however, interference was overcome with dose adjustment across a range of rS/HA doses. Specifically, higher rS dose ( >20ug), in a dose dependent fashion, overcame HA interference, closely matching standalone rS IgG reference responses (GMEU 16,818), whereas lower, intermediate HA dose overcame rS interference, closely matching standalone HA reference HAI responses for H3N2 (GMT 145), H1N1 (GMT 134), and B-Victoria (GMT 66); while modestly (at least 34%) lower than the reference B-Yamagata response (GMT 101). Conclusion CIC formulations were well tolerated and immunogenic, with various dose combinations achieving response comparable to standalone vaccines. Disclosures Vivek Shinde, MD, MPH, Novavax Inc.: Stocks/Bonds Wayne Woo, MS, Novavax Inc.: Stocks/Bonds Sharon Liu, n/a, Novavax Inc.: Stocks/Bonds Sara Cook, n/a, Novavax Inc.: Stocks/Bonds Zenaida Santiago, n/a, Novavax Inc.: Stocks/Bonds Susan Neal, n/a, Novavax Inc.: Stocks/Bonds Joyce S. Plested, n/a, Novavax Inc.: Stocks/Bonds Tim Vincent, n/a, Novavax Inc.: Stocks/Bonds Mingzhu Zhu, n/a, Novavax Inc.: Stocks/Bonds Shane Cloney-Clark, n/a, Novavax Inc.: Stocks/Bonds Iksung Cho, MS, Novavax Inc.: Stocks/Bonds Lou Fries, n/a, Novavax Inc.: Stocks/Bonds Greg Glenn, n/a, Novavax Inc.: Stocks/Bonds.

Dilhara Karunaratne,1 Nisal Karunaratne,2 Jade Wilmot,3 Tim Vincent,2 Juliet Wright,2 Nadia Mahmood,4 Alice Tang,5 Amir H Sam,5 Malcolm Reed,2 David Howlett1 1Eastbourne District General Hospital, Eastbourne, BN21 2UD, UK; 2Brighton and Sussex Medical School, Brighton, BN1 9PX, UK; 3Warwick Medical School, Coventry, CV4 7HL, UK; 4Royal Sussex County Hospital, Brighton, BN2 5BE, UK; 5Imperial College London, Charing Cross Campus, London, W6 8RP, UKCorrespondence: Dilhara KarunaratneEastbourne District General Hospital, King’s Drive, Eastbourne, BN21 2UD, UKTel +44 300 151 4500Fax +44 1323 43579Email diliekaru@yahoo.co.ukAbstract: This paper describes the development and use of the bespoke digital learning resource CAPSULE (Clinical and Professional Studies Unique Learning Environment) which was launched UK wide in May 2020 to facilitate the delivery of core learning content for UK medical students during the COVID-19 pandemic. CAPSULE is a digital learning resource comprising case-based scenarios and multiple-choice questions, encompassing all undergraduate medical specialities and supported by a pan-speciality editorial board. Following the COVID-19 pandemic lockdown and loss of face-to-face learning opportunities, CAPSULE was made available to all UK medical schools in May 2020. Following a global content review and edit and UK wide rollout, over 41,000 medical students and 3200 faculty registered as users. Approximately 1.5 million cases were completed in the first 12 months of use by up to 4500 distinct monthly users. Feedback from both students and faculty has been highly positive. CAPSULE continues to be used within UK medical schools and has allowed an entire cohort of medical students to access core curriculum content and progress their studies during the COVID-19 pandemic. Future directions may include further integration into UK medical school curricula, enhancement of platform functionality and potential expansion on an international scale.Keywords: CAPSULE, COVID-19, digital learning platform, UK medical school

This work presents solutions to Challenge 2 within the Air Force Research Laboratory Materials Inform Data-Driven Design for AM Structures (MID3AS) AM (Additive Manufacturing) Challenge. The solutions are for quasi-steady-state and transient Nth-track cross-sectional predictions as a function of scan paths. Tracks are deposited successively to produce a pad and overlap each other; their cross section is defined using four dimensions: total depth, remelt depth, half width, and width increment due to the addition of the latest (Nth) track. There are six pads for which the pad dimensions, build height, power, scan speed, hatch spacing, and number of tracks are varied. There also are two thin walls that consist of 10 single tracks deposited on top of each other. The track cross sections are to be reported at three measurement planes defined orthogonal to the scan path at varying distances from the start of a track in the quasi-steady-state and transient melt-pool regions. The predictions are generated using the Additive Manufacturing Parameter Predictor (AMP2) software that performed multi-scale simulations for the six pads and two thin walls. Two types of melt-pool simulations were performed: a quasi-steady-state, thermal-computational fluid dynamics simulation and a transient thermal simulation. The statistics of track dimensions were estimated using discrete element modeling to predict the local variation in recoat powder density and correcting for the additive mass consolidated by a track cross section accordingly. Applied Optimization, Inc. achieved third place for the accuracy of predictions required by Challenge 2 in the MID3AS AM Challenge.

This work presents a comparison of simulation results with the experimental data for four of the six challenges within the National Institute of Standards and Technology (NIST) Additive Manufacturing (AM) Benchmark Test Series (AM Bench) problem AMB2018-02. This comparison is akin to a test case to assess the technology maturity level (TML) for the AM predictive capabilities that can be utilized to improve AM products in the industry. The solutions are for the prediction of melt-pool geometry, cooling rate, solidification grain shapes, and their 3D structure. These results were obtained using the Additive Manufacturing Parameter Predictor (AMP2) software. AMP2 is an Integrated Computational Materials Engineering (ICME) suite of software developed by Applied Optimization, Inc. (AO). The melt-pool geometry is obtained using a thermal-computational fluid dynamics (CFD) solution of melt-pool physics. The melt-pool geometry, mean track cross section, 3D distribution of thermal gradient, and the liquid-to-solid interface velocity are predicted by the thermal-CFD model and utilized as input for the solidification grain structure computation. The grain shapes and 3D structure are modeled using cellular automata (CA). AO received a second-place award for predicting the grain structure within three single laser tracks on a bare plate of alloy Inconel 625 (IN625).

The complex, multi-faceted physics of laser-based additive metals processing tends to demand high-fidelity models and costly simulation tools to provide predictions accurate enough to aid in selecting process parameters. Of particular difficulty is the accurate determination of melt pool shape and size, which are useful for predicting lack-of-fusion, as this typically requires an adequate treatment of thermal and fluid flow. In this article we describe a novel numerical simulation tool which aims to achieve a balance between accuracy and cost. This is accomplished by making simplifying assumptions regarding the behavior of the gas-liquid interface for processes with a moderate energy density, such as Laser Engineered Net Shaping (LENS). The details of the implementation, which is based on the solver simpleFoam of the well-known software suite OpenFOAM, are given here and the tool is verified and validated for a LENS process involving Ti-6Al-4V. The results indicate that the new tool predicts width and height of a deposited track to engineering accuracy levels.

IntroductionMobile applications (Apps) are popular in medical education; yet, the actual benefits for students are yet to be formally researched. Clinical And Professional Studies Unique Learning Environment (CAPSULE) is an App created by Brighton and Sussex Medical School. The App provides 650 cases offered to students in their final two years of the undergraduate programme. The App performed consistently well in student feedback, and therefore, a study into the educational benefits of the App was constructed.MethodsA cross-sectional study was performed following two years of use by students to investigate the relationship between App usage and decile ranking.ResultsThe study found that the students who completed more cases tended to score higher per case (p value=0.0037). The study also found a trend between having higher case scores and being part of a stronger decile (p value=0.019).ConclusionsGreater App usage was linked with performing better in the App itself and this was further associated with being in a stronger decile rank. From a user perspective, the data generated from the App could help with identifying students who are underperforming or help students to recognise areas on which they need to focus.

BACKGROUND: As the health care education landscape in the UK changes rapidly and dramatically, collaboration across institutions bridging undergraduate and postgraduate fields is increasingly necessary. Collaboration entails both risks and benefits. There is a paucity of advice on how to ensure collaborative projects in medical education are effective. There is a paucity of advice on how to ensure collaborative projects in medical education are effective CONTEXT: In 2011 three medical schools began a collaborative project along with NHS Education for Scotland (NES) to modify, develop and deliver a medical school version of the NES foundation programme ePortfolio, called UMeP. The underlying principal was the introduction of an authentic ePortfolio early in undergraduate life. The challenge of three diverse medical schools with significantly different curricula and assessment approaches working together with a single postgraduate ePortfolio was complex and demanding. DISCUSSION: We reveal the complexities of collaboration on education projects and draw on our experiences to provide illustrative examples of collaboration. Despite the increased complexity and need for compromise, we argue that successful collaborative partnerships are key to maximising the circumstances in which education innovation can be successful, and create the potential for robust evaluation and research.

While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control. These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.

Objective: To identify clinical predictors of mortality in HIV-2-infected individuals that may be used in place of CD4 count or plasma viral load (PVL) to guide treatment management in resource-limited settings. Methods: A prospective community cohort study of HIV-infected and HIV-negative individuals in a rural area of Guinea-Bissau has been ongoing since 1989. In 2003 participants were invited for a clinical examination and blood tests. They were followed-up for vital status until 2010. Antiretroviral treatment (ART) became available in 2007. Cox regression was used to examine the association of clinical measures (World Health Organization (WHO) stage, body mass index (BMI), mid-upper arm circumference (MUAC), and WHO performance scale) measured in 2003 with subsequent mortality. Results: In 2003, 146 HIV-2-infected individuals (68% women; mean age 56 years) were examined. Over the next 7 years, 44 (30%) died. BMI

While well documented in human immunodeficiency virus (HIV)-1, neurologic sequelae have not been systematically evaluated in HIV-2. After excluding for confounding comorbidities, 67 individuals from a rural cohort in Guinea-Bissau (22 HIV-2 participants, 45 seronegative controls) were evaluated. HIV + individuals were divided into CD4

OBJECTIVES: To assess changes in HIV incidence and prevalence in Caió, a rural area of Guinea-Bissau, between 1990 and 2007. DESIGN: Three cross-sectional community surveys. METHODS: In 1990, 1997, and 2007, surveys were conducted among adults. The prevalence of HIV-1 and of HIV-2 was estimated for each survey, and incidence rates were calculated for the first (1990-1997) and second period (1997-2007). RESULTS: The HIV-1 incidence was approximately 4.5/1000 person-years in the two periods, whereas the HIV-2 incidence decreased from 4.7 (95% confidence interval 3.6-6.2) in the first to 2.0 (95% confidence interval 1.4-3.0) per 1000 person-years in the second period (P < 0.001). HIV-1 prevalence rose from 0.5% in 1990 to 3.6% in 2007, and HIV-2 prevalence decreased from 8.3% in 1990 to 4.7% in 2007. HIV-1 prevalence was less than 2% in 15 to 24 year olds in all surveys and was highest (7.2%) in 2007 among 45 to 54 year olds. The HIV-2 prevalence was fivefold higher in older subjects (> or =45 yr) compared with those less than 45 years in both sexes in 2007. CONCLUSIONS: HIV-1 incidence is stable, and its prevalence is increasing, whereas HIV-2 incidence and prevalence are both declining. In contrast with what has been observed in other sub-Saharan countries, HIV-1 prevalence is lower in younger age groups than older age groups.

The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged

Numerous studies have been undertaken demonstrating that online learning is an effective teaching tool, working best when combined with more conventional teaching methods. There is a paucity of data both examining the longitudinal blending of an e-module with more conventional modes of curriculum delivery and also relating to the time and financial costs involved in successful delivery of such a module. The study reported in this article was performed over an academic year in a cohort of 101 year 5 medical students. It demonstrates that there are significant set-up costs involved in designing and implementing an online module, although these costs will diminish following initial set-up. Surveys performed throughout the year demonstrated consistently high levels of student satisfaction, with appreciation of the educational benefits provided by e-learning. Successful clinician engagement and effective IT support are essential ingredients to success. Future research is likely to focus on outcome evaluations of e-learning and how it may affect learner knowledge, skills or attitudes.

We investigated the association between beta2-microglobulin, neopterin, serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), CD4 count, and plasma viremia with survival in 133 HIV-2-infected villagers and 160 controls living in rural Guinea-Bissau. Subjects were recruited in 1991 and visited at home every 3-6 months until 1998. Median beta2-microglobulin, neopterin, and suPAR were significantly higher and CD4% significantly lower among HIV-2-infected individuals than controls. Thirty-one HIV-2-infected individuals died and 7 were lost to follow-up. beta2-Microglobulin, CD4%, and plasma viral load were associated independently with survival in multivariate analyses. Neopterin and suPAR did not reach statistical significance. These findings suggest that immune activation is central to the pathogenesis of HIV. They also have important implications for resource-poor settings where CD4 count and plasma viral load are unaffordable.

The search for a framework of literacy that can accommodate a broader sense of what it means to be literate in American mass culture, recalls not only such imports as Huxley's, Horkheimer's, Adorno's, Ortega y Gasset's, and T. S. Eliot's elitist worries of the 1930s that high culture was in jeopardy; that decade also saw great numbers of American "advanced intellectuals" as Philip Rahv called them (41), from all across the political spectrum, struggling with the problem that a twenty-nine-year-old Van Wyck Brooks had described as early as 1915. How could America reconcile the division between what Brooks called (he actually coined the terms) "highbrow" and "lowbrow" to create a cultural middle ground where "the poetry of life should serve, in harnessing thought and action together, [to turn] life into a disinterested adventure" (15)? For Brooks in 1915, such a "disinterested adventure" involved an individual expressing "the better intuitions and desires of his age and place" (18). This meant a close and well understood relationship between the individual and "some visible or invisible host about him, since the mind is a flower that has an organic connection with the soil from which it springs" (18). By the 1930s, as the country reeled from cataclysmic war to economic and technological boom to deep depression, the relationship between the mind and the soil from which it springs was not only infinitely more complex than even a thinker of Brooks's magnitude could fairly comprehend in 1915, but the split between the mind and the world, along with the various classes of society, seemed problematic at best, and perhaps unbridgeable at worst. For Brooks, solving the political division between highbrow and lowbrow depended in large part on where the highbrow intended to position itself along a continuum of a number of key philosophical, aesthetic, and cultural issues: But certainly no true social revolution will ever be possible in America till a race of artists, profound and sincere, has brought us face to face with our own experience and set working in that experience the leaven of the highest culture. For it is exalted desires that give their validity to revolutions, and exalted desires take form only in exalted souls. But has there ever been a time when masses of men have conceived these desires without leaders to formulate them and press them home? (158-59) Himself a 1907 graduate of Harvard, such a position might be seen as coming naturally to Brooks; but, as later thinkers were to discover-from the Frankfurt School of the 1930s to the New York Intellectuals of the 1950s to the New Left of the 1960s-the American ethos does not take very kindly to the pronouncements of cultural mandarins. What Brooks described as an America of "unconscious life, swept by ground-swells of half-conscious emotion" and as a "welter of life which has not been worked into an organism, into which fruitful values and standards of humane economy have not been introduced" (78), could also be viewed as an America, at least by the 1920s, so thoroughly steeped in the guiding belief of consumer choice, that cultural strictures from above were likely to be met-as they are today-with that deepest of "fruitful" American values, "to each his own." In fact, as Richard Wightman Fox and T. J. Jackson Lears point out (1983), it was the very "exalted desires" of "exalted souls" for a life of greater intensity and personal fulfillment that helped to create the therapeutic megastate that Henry Adams, Thorstein Veblen, and others foresaw with horror at the turn of the century. With the emergence of a commercial broadcasting system (recently explored with great skill by Robert McChesney), greater mobility, and a greater percentage of individuals working in salaried jobs and professions, individual pursuit of pleasure and fulfillment assumed hegemonic proportions in the Gramscian sense of the term. It mattered little whether such private pursuits involved high culture or nickelodeons, since the underlying cultural principles had shifted from sacrifice, externality, and transcendence, to comfort, self-absorption, and social adjustment. …

The present mass culture can be characterized by its resistance to meaning or, perhaps more accurately, its resistance to a clear separation between information and meaning. A central goal of literacy education will be to develop minds that can create meaning, not merely become more proficient at processing received information. Faced with the trend toward corporate takeover of culture—begun in earnest in the 1930s and reaching global proportions today—where can educators turn for help in the search for a new literacy that can begin to address the struggle for control of culture that will be a central issue for democratic societies in the years ahead?

Background Human T-Lymphotropic Virus Type 1 (HTLV-1) infection causes lethal adult T-cell leukemia (ATL) and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest prevalence in West Africa (5%) has been reported in Caio, a rural area in the North-West of Guinea-Bissau. It is not known which HTLV-1 variants are present in this community. Sequence data can provide insights in the molecular epidemiology and help to understand the origin and spread of HTLV-1. Objective To gain insight into the molecular diversity of HTLV-1 in West Africa. Methods HTLV-1 infected individuals were identified in community surveys between 1990–2007. The complete Long Terminal Repeat (LTR) and p24 coding region of HTLV-1 was sequenced from infected subjects. Socio-demographic data were obtained from community census and from interviews performed by fieldworkers. Phylogenetic analyses were performed to characterize the relationship between the Caio HTLV-1 and HTLV-1 from other parts of the world. Results LTR and p24 sequences were obtained from 72 individuals (36 LTR, 24 p24 only and 12 both). Consistent with the low evolutionary change of HTLV-1, many of the sequences from unrelated individuals showed 100% nucleotide identity. Most (45 of 46) of the LTR sequences clustered with the Cosmopolitan HTLV-1 subtype 1a, subgroup D (1aD). LTR and p24 sequences from two subjects were divergent and formed a significant cluster with HTLV-1 subtype 1g, and with the most divergent African Simian T-cell Lymphotropic Virus, Tan90. Conclusions The Cosmopolitan HTLV-1 1aD predominates in this rural West African community. However, HTLV-1 subtype 1g is also present. This subtype has not been described before in West Africa and may be more widespread than previously thought. These data are in line with the hypothesis that multiple monkey-to-man zoonotic events are contributing to HTLV-1 diversity., Author Summary Human T-Lymphotropic Virus type 1 (HTLV-1) affects millions of people worldwide. It is very similar to Simian T-Lymphotropic Virus, a virus that circulates in monkeys. HTLV-1 causes a lethal form of leukemia (Adult T-cell Leukemia) and a debilitating neurological syndrome (HTLV-associated myelopathy/tropical spastic paraparesis) in approximately 5% of infected people. Based on sequence variation, HTLV-1 can be divided into 7 subtypes (1a–1g) with the Cosmopolitan subtype 1a further subdivided into subgroups (A–E). We examined HTLV-1 diversity in a rural area in Guinea-Bissau, a country in West Africa with a high HTLV-1 prevalence (5%). We found that most viruses belong to the Cosmopolitan subtype 1a, subgroup D, but 2 viruses belonged to subtype 1g. This subtype had thus far only been found in monkey hunters in Cameroon, who were probably recently infected by monkeys. Our findings indicate that this subtype has spread beyond Central Africa. An important, unresolved question is whether persons with this subtype were infected by monkeys or through human-to-human transmission.

Background: \ud Survival of people with HIV-2 and HTLV-1 infection is better than that of HIV-1 infected people, but long-term follow-up data are rare. We compared mortality rates of HIV-1, HIV-2, and HTLV-1 infected subjects with those of retrovirus-uninfected people in a rural community in Guinea-Bissau.\ud \ud Methods: \ud In 1990, 1997 and 2007, adult residents (aged ≥15 years) were interviewed, a blood sample was drawn and retroviral status was determined. An annual census was used to ascertain the vital status of all subjects. Cox regression analysis was used to estimate mortality hazard ratios (HR), comparing retrovirus-infected versus uninfected people.\ud \ud Results: \ud A total of 5376 subjects were included; 197 with HIV-1, 424 with HIV-2 and 325 with HTLV-1 infection. The median follow-up time was 10.9 years (range 0.0–20.3). The crude mortality rates were 9.6 per 100 person-years of observation (95% confidence interval 7.1-12.9) for HIV-1, 4.1 (3.4–5.0) for HIV-2, 3.6 (2.9–4.6) for HTLV-1, and 1.6 (1.5–1.8) for retrovirus-negative subjects. The HR comparing the mortality rate of infected to that of uninfected subjects varied significantly with age. The adjusted HR for HIV-1 infection varied from 4.0 in the oldest age group (≥60 years) to 12.7 in the youngest (15–29 years). The HR for HIV-2 infection varied from 1.2 (oldest) to 9.1 (youngest), and for HTLV-1 infection from 1.2 (oldest) to 3.8 (youngest).\ud \ud Conclusions: \ud HTLV-1 infection is associated with significantly increased mortality. The mortality rate of HIV-2 infection, although lower than that of HIV-1 infection, is also increased, especially among young people.

Overall, the time to AIDS after HIV-2 infection is longer than with HIV-1, and many individuals infected with HIV-2 virus remain healthy throughout their lives. Multiple HLA and KIR gene products have been implicated in the control of HIV-1, but the effect of variation at these loci on HIV-2 disease is unknown. We show here for the first time that HLA-B*1503 is associated significantly with poor prognosis after HIV-2 infection and that HLA-B*0801 is associated with susceptibility to infection. Interestingly, previous data indicate that HLA-B*1503 is associated with low viral loads in HIV-1 clade B infection but has no significant effect on viral load in clade C infection. In general, alleles strongly associated with HIV-1 disease showed no effect in HIV-2 disease. These data emphasize the unique nature of the effects of HLA and HLA/KIR combinations on HIV-2 immune responses relative to HIV-1, which could be related to their distinct clinical course.

Background HTLV-1 is endemic in Guinea-Bissau, and the highest prevalence in the adult population (5.2%) was observed in a rural area, Caió, in 1990. HIV-1 and HIV-2 are both prevalent in this area as well. Cross-sectional associations have been reported for HTLV-1 with HIV infection, but the trends in prevalence of HTLV-1 and HIV associations are largely unknown, especially in Sub Saharan Africa. In the current study, data from three cross-sectional community surveys performed in 1990, 1997 and 2007, were used to assess changes in HTLV-1 prevalence, incidence and its associations with HIV-1 and HIV-2 and potential risk factors. Results HTLV-1 prevalence was 5.2% in 1990, 5.9% in 1997 and 4.6% in 2007. Prevalence was higher among women than men in all 3 surveys and increased with age. The Odds Ratio (OR) of being infected with HTLV-1 was significantly higher for HIV positive subjects in all surveys after adjustment for potential confounding factors. The risk of HTLV-1 infection was higher in subjects with an HTLV-1 positive mother versus an uninfected mother (OR 4.6, CI 2.6-8.0). The HTLV-1 incidence was stable between 1990-1997 (Incidence Rate (IR) 1.8/1,000 pyo) and 1997-2007 (IR 1.6/1,000 pyo) (Incidence Rate Ratio (IRR) 0.9, CI 0.4-1.7). The incidence of HTLV-1 among HIV-positive individuals was higher compared to HIV negative individuals (IRR 2.5, CI 1.0-6.2), while the HIV incidence did not differ by HTLV-1 status (IRR 1.2, CI 0.5-2.7). Conclusions To our knowledge, this is the largest community based study that has reported on HTLV-1 prevalence and associations with HIV. HTLV-1 is endemic in this rural community in West Africa with a stable incidence and a high prevalence. The prevalence increases with age and is higher in women than men. HTLV-1 infection is associated with HIV infection, and longitudinal data indicate HIV infection may be a risk factor for acquiring HTLV-1, but not vice versa. Mother to child transmission is likely to contribute to the epidemic.

Summary HIV-2 and HTLV-1 infection are both associated with increased mortality, but the causes of death are not well known. Relatives of 84 deceased persons from a rural part of Guinea-Bissau were interviewed using a standardised verbal autopsy questionnaire in the context of a large longitudinal community cohort study. The results were reviewed by two doctors to conclude cause of death. A cause of death was agreed upon for 49/84 subjects. Nineteen of these 49 were infected with HIV-2 alone and 7 with both HIV-2 and HTLV-1. Among these, the main causes of death were pulmonary tuberculosis (n = 5), AIDS (n = 5), cerebrovascular accident (n = 5), sepsis (n = 3) and hepatocellular carcinoma (n = 2). Death associated with traditional HIV-related causes were implicated in 13/26 (50%) of those with HIV-2.

Aim: To review the initial experience of blending a variety of online educational techniques with traditional face to face or contact-based teaching methods to deliver final year undergraduate radiology content at a UK Medical School. Materials and methods: The Brighton and Sussex Medical School opened in 2003 and offers a 5-year undergraduate programme, with the final 5 spent in several regional centres. Year 5 involves several core clinical specialities with onsite radiology teaching provided at regional centres in the form of small-group tutorials, imaging seminars and also a one-day course. An online educational module was introduced in 2007 to facilitate equitable delivery of the year 5 curriculum between the regional centres and to support students on placement. This module had a strong radiological emphasis, with a combination of imaging integrated into clinical cases to reflect everyday practice and also dedicated radiology cases. For the second cohort of year 5 students in 2008 two additional online media-rich initiatives were introduced, to complement the online module, comprising imaging tutorials and an online case discussion room. Results: In the first year for the 2007/2008 cohort, 490 cases were written, edited and delivered via the Medical School managed learning environment as part of the online module. 253 cases contained a form of image media, of which 195 cases had a radiological component with a total of 325 radiology images. Important aspects of radiology practice (e. g. consent, patient safety, contrast toxicity, ionising radiation) were also covered. There were 274,000 student hits on cases the first year, with students completing a mean of 169 cases each. High levels of student satisfaction were recorded in relation to the online module and also additional online radiology teaching initiatives. Conclusion: Online educational techniques can be effectively blended with other forms of teaching to allow successful undergraduate delivery of radiology. Efficient IT links and good image quality are essential ingredients for successful student/clinician engagement.

We report the possible transmission of drug]resistant human immunodeficiency virus type 2. A 66]year]old woman from rural Guinea Bissau who had no obvious antiretroviral exposure was found to harbor a variant with the multidrug]resistance mutation Q151M. Finding this mutation among a drug]naive population presents an important public health issue that needs to be addressed for treatment to be effective.

HIV-2 infection in the majority of infected subjects follows an attenuated disease course that distinguishes it from infection with HIV-1. Antigen-specific T cells are pivotal in the management of chronic viral infections but are not sufficient to control viral replication in HIV-1-positive subjects, and their function in HIV-2 infection is not fully established. In a community-based cohort of HIV-2 long-term nonprogressors in rural Guinea-Bissau, we performed what we believe is the first comprehensive analysis of HIV-2-specific immune responses. We demonstrate that Gag is the most immunogenic protein. The magnitude of the IFN-gamma immune response to the HIV-2 proteome was inversely correlated with HIV-2 viremia, and this relationship was specifically due to the targeting of Gag. Furthermore, patients with undetectable viremia had greater Gag-specific responses compared with patients with high viral replication. The most frequently recognized peptides clustered within a defined region of Gag, and responses to a single peptide in this region were associated with low viral burden. The consistent relationship between Gag-specific immune responses and viremia control suggests that T cell responses are vital in determining the superior outcome of HIV-2 infection. A better understanding of how HIV-2 infection is controlled may identify correlates of effective protective immunity essential for the design of HIV vaccines.

BackgroundIn urban Guinea-Bissau, adults with a vaccinia scar had better survival but also a higher prevalence of HIV-2 infection. We therefore investigated the association between vaccinia scar and survival and HIV infection in a rural area of Guinea-Bissau.Methodology/principal findingsIn connection with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in 193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was assessed after 2(1/2)-3 years of follow-up. The analyses were adjusted for age, sex, village, and HIV status. The prevalence of vaccinia scar was associated with age, village, and HIV-2 status but not with sex and schooling. Compared with individuals without any scar, individuals with a vaccinia scar had better survival (mortality rate ratio (MR) = 0.22 (95% CI 0.08-0.61)), the MR being 0.19 (95% CI 0.06-0.57) for women and 0.40 (95% CI 0.04-3.74) for men. Estimates were similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2 prevalence was higher among individuals with a vaccinia scar compared to individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36)).ConclusionThe present study supports the hypothesis that vaccinia vaccination may have a non-specific beneficial effect on adult survival.

Background HTLV-1 is endemic in parts of Africa and the highest prevalence (5%) in West Africa has been reported in Caio, a rural area in Guinea-Bissau. It is unknown which HTLV-1 subtypes are present in this community. Objective To compare local HTLV-1 sequence variation and to describe the phylogeny of the virus in the Caio population.

Background Mobile technology is increasingly being used by clinicians to access up-to-date information for patient care. These offer learning opportunities in the clinical setting for medical students but the underlying pedagogic theories are not clear. A conceptual framework is needed to understand these further. Our initial questions were how the medical students used the technology, how it enabled them to learn and what theoretical underpinning supported the learning. Methods 387 medical students were provided with a personal digital assistant (PDA) loaded with medical resources for the duration of their clinical studies. Outcomes were assessed by a mixed-methods triangulation approach using qualitative and quantitative analysis of surveys, focus groups and usage tracking data. Results Learning occurred in context with timely access to key facts and through consolidation of knowledge via repetition. The PDA was an important addition to the learning ecology rather than a replacement. Contextual factors impacted on use both positively and negatively. Barriers included concerns of interrupting the clinical interaction and of negative responses from teachers and patients. Students preferred a future involving smartphone platforms. Conclusions This is the first study to describe the learning ecology and pedagogic basis behind the use of mobile learning technologies in a large cohort of undergraduate medical students in the clinical environment. We have developed a model for mobile learning in the clinical setting that shows how different theories contribute to its use taking into account positive and negative contextual factors. The lessons from this study are transferable internationally, to other health care professions and to the development of similar initiatives with newer technology such as smartphones or tablet computers.