Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdon: multicentre cohort study

Objectives: To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. Design: Multicentre cohort study. Setting: Six large HIV treatment centres in southeast England. Participants: All individuals seen for care between 1 January 1996 and 31 December 2002. Main outcome measures: Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. Results: Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3. Conclusions: The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients

Seoul Virus and Hantavirus Disease, Shenyang, People’s Republic of China

This outbreak was caused by the virus circulating in local wild rats through infection of laboratory rats

Enforced Expression of HOXB4 in Human Embryonic Stem Cells Enhances the Production of Hematopoietic Progenitors but Has No Effect on the Maturation of Red Blood Cells

We have developed a robust, Good Manufacturing Practice-compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult globins, and they do not enucleate efficiently. Based on previous studies, we predicted that activation of exogenous HOXB4 would increase the production of hematopoietic progenitor cells (HPCs) from hPSCs and hypothesized that it might also promote the production of more mature, definitive RBCs. Using a tamoxifen-inducible HOXB4-ERT2 expression system, we first demonstrated that activation of HOXB4 does increase the production of HPCs from hPSCs as determined by colony-forming unit culture activity and the presence of CD43+CD34+ progenitors. Activation of HOXB4 caused a modest, but significant, increase in the proportion of immature CD235a+/CD71+ erythroid cells. However, this did not result in a significant increase in more mature CD235a+/CD71− cells. RBCs produced in the presence of enhanced HOXB4 activity expressed embryonic (ε) and fetal (γ) but not adult (β) globins, and the proportion of enucleated cells was comparable to that of the control cultures. We conclude that programming with the transcription factor HOXB4 increases the production of hematopoietic progenitors and immature erythroid cells but does not resolve the inherent challenges associated with the production of mature adult-like enucleated RBCs

Integrating cancer survivors' experiences into UK cancer registries: design and development of the ePOCS system (electronic Patient-reported Outcomes from Cancer Survivors)

BACKGROUND: Understanding the psychosocial challenges of cancer survivorship, and identifying which patients experience ongoing difficulties, is a key priority. The ePOCS (electronic patient-reported outcomes from cancer survivors) project aims to develop and evaluate a cost-efficient, UK-scalable electronic system for collecting patient-reported outcome measures (PROMs), at regular post-diagnostic timepoints, and linking these with clinical data in cancer registries. METHODS: A multidisciplinary team developed the system using agile methods. Design entailed process mapping the system's constituent parts, data flows and involved human activities, and undertaking usability testing. Informatics specialists built new technical components, including a web-based questionnaire tool and tracking database, and established component-connecting data flows. Development challenges were overcome, including patient usability and data linkage and security. RESULTS: We have developed a system in which PROMs are completed online, using a secure questionnaire administration tool, accessed via a public-facing website, and the responses are linked and stored with clinical registry data. Patient monitoring and communications are semiautomated via a tracker database, and patient correspondence is primarily Email-based. The system is currently honed for clinician-led hospital-based patient recruitment. CONCLUSIONS: A feasibility test study is underway. Although there are possible challenges to sustaining and scaling up ePOCS, the system has potential to support UK epidemiological PROMs collection and clinical data linkage

Multifunctional biomaterials from the sea: Assessing the effects of chitosan incorporation into collagen scaffolds on mechanical and biological functionality

Natural biomaterials such as collagen show promise in tissue engineering applications due to their inherent bioactivity. The main limitation of collagen is its low mechanical strength and somewhat unpredictable and rapid degradation rate; however, combining collagen with another material, such as chitosan, can reinforce the scaffold mechanically and may improve the rate of degradation. Additionally, the high cost and the risk of prion transmission associated with mammal-derived collagen has prompted research into alternative sources such as marine-origin collagen. In this context, the overall goal of this study was to determine if the incorporation of chitosan into collagen scaffolds could improve the mechanical and biological properties of the scaffold. In addition the study assessed if collagen, derived from salmon skin (marine), can provide an alternative to collagen derived from bovine tendon (mammal) for tissue engineering applications. Scaffold architecture and mechanical properties were assessed as well as their ability to support mesenchymal stem cell growth and differentiation. Overall, the addition of chitosan to bovine and salmon skin-derived collagen scaffolds improved the mechanical properties, increasing the compressive strength, swelling ratio and prolonged the degradation rate. Mesenchymal stem cell (MSC) attachment and proliferation was most improved on the bovine-derived collagen scaffold containing a 75:25 ratio of collagen:chitosan, and when MSC osteogenic and chondrogenic potential on the scaffold was assessed, a significant increase in calcium production (p < 0.001) and sulfated glycosaminoglycan (sGAG) production (p < 0.001) was observed respectively. Regardless of chitosan content, the bovine-derived collagen scaffolds out-performed the salmon skin-derived collagen scaffolds, displaying a larger pore size and higher percentage porosity, more regular architecture, higher compressive modulus, a greater capacity for water uptake and allowed for more MSC proliferation and differentiation. This versatile scaffold incorporating the marine biomaterial chitosan show great potential as appropriate platforms for promoting orthopaedic tissue repair while the use of salmon skin-derived collagen may be more suitable in the repair of soft tissues such as skin.This work was funded by Science Foundation Ireland (SFI) through the Research Frontiers Programme (Grant No. 11/RFP/ENM/3063) and by the European Regional Development Fund (ERDF) through INTERREG 2007-2013 Program (POCTEP project 0687_NOVOMAR_1_P). Bovine collagen materials were provided by Integra Life Sciences, Inc. through a Material Transfer Agreement. Salmon skins were kindly offered by Pingo Doce, Braga (Portugal)

Publication bias in gastroenterological research – a retrospective cohort study based on abstracts submitted to a scientific meeting

BACKGROUND: The aim of this study was to examine the determinants of publication and whether publication bias occurred in gastroenterological research. METHODS: A random sample of abstracts submitted to DDW, the major GI meeting (1992–1995) was evaluated. The publication status was determined by database searches, complemented by a mailed survey to abstract authors. Determinants of publication were examined by Cox proportional hazards model and multiple logistic regression. RESULTS: The sample included abstracts on 326 controlled clinical trials (CCT), 336 other clinical research reports (OCR), and 174 basic science studies (BSS). 392 abstracts (47%) were published as full papers. Acceptance for presentation at the meeting was a strong predictor of subsequent publication for all research types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate analysis, multi-center status was found to predict publication (OR 2.8, 95% CI 1.6–4.9). There was no significant association between direction of study results and subsequent publication. Studies were less likely to be published in high impact journals if the results were not statistically significant (OR 0.5, 95 CI 95% 0.3–0.6). The author survey identified lack of time or interest as the main reason for failure to publish. CONCLUSIONS: Abstracts which were selected for presentation at the DDW are more likely to be followed by full publications. The statistical significance of the study results was not found to be a predictor of publication but influences the chances for high impact publication

Individual and culture-level components of survey response styles: a multi-level analysis using cultural models of selfhood

Variations in acquiescence and extremity pose substantial threats to the validity of cross-cultural research that relies on survey methods. Individual and cultural correlates of response styles when using two contrasting types of response mode were investigated, drawing on data from 55 cultural groups across 33 nations. Using seven dimensions of self-other relatedness that have often been confounded within the broader distinction between independence and interdependence, our analysis yields more specific understandings of both individual- and culture-level variations in response style. When using a Likert scale response format, acquiescence is strongest among individuals seeing themselves as similar to others, and where cultural models of selfhood favour harmony, similarity with others and receptiveness to influence. However, when using Schwartz’s (2007) portrait-comparison response procedure, acquiescence is strongest among individuals seeing themselves as self-reliant but also connected to others, and where cultural models of selfhood favour self-reliance and self-consistency. Extreme responding varies less between the two types of response modes, and is most prevalent among individuals seeing themselves as self-reliant, and in cultures favouring self-reliance. Since both types of response mode elicit distinctive styles of response, it remains important to estimate and control for style effects to ensure valid comparisons

Cost effectiveness of a multi-stage return to work program for workers on sick leave due to low back pain, design of a population based controlled trial [ISRCTN60233560]

BACKGROUND: To describe the design of a population based randomized controlled trial (RCT), including a cost-effectiveness analysis, comparing participative ergonomics interventions between 2–8 weeks of sick leave and Graded Activity after 8 weeks of sick leave with usual care, in occupational back pain management. METHODS: DESIGN: An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain. Interventions used are 1. Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist. 2. Graded Activity based on cognitive behavioural principles by a physiotherapist. 3. Usual care, provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain. The primary outcome measure is return to work. Secondary outcome measures are pain intensity, functional status and general improvement. Intermediate variables are kinesiophobia and pain coping. The cost-effectiveness analysis includes the direct and indirect costs due to low back pain. The outcome measures are assessed before randomization (after 2–6 weeks on sick leave) and 12 weeks, 26 weeks and 52 weeks after first day of sick leave. DISCUSSION: The combination of these interventions has been subject of earlier research in Canada. The results of the current RCT will: 1. crossvalidate the Canadian findings in an different sociocultural environment; 2. add to the cost-effectiveness on treatment options for workers in the sub acute phase of low back pain. Results might lead to alterations of existing (inter)national guidelines

A-6G and A-20C Polymorphisms in the Angiotensinogen Promoter and Hypertension Risk in Chinese: A Meta-Analysis

BACKGROUND: Numerous studies in Chinese populations have evaluated the association between the A-6G and A-20C polymorphisms in the promoter region of angiotensinogen gene and hypertension. However, the results remain conflicting. We carried out a meta-analysis for these associations. METHODS AND RESULTS: Case-control studies in Chinese and English publications were identified by searching the MEDLINE, EMBASE, CNKI, Wanfang, CBM, and VIP databases. The random-effects model was applied for dichotomous outcomes to combine the results of the individual studies. We finally selected 24 studies containing 5932 hypertensive patients and 5231 normotensive controls. Overall, we found significant association between the A-6G polymorphism and the decreased risk of hypertension in the dominant genetic model (AA+AG vs. GG: P=0.001, OR=0.71, 95%CI 0.57-0.87, P(heterogeneity)=0.96). The A-20C polymorphism was significantly associated with the increased risk for hypertension in the allele comparison (C vs. A: P=0.03, OR=1.14, 95%CI 1.02-1.27, P(heterogeneity)=0.92) and recessive genetic model (CC vs. CA+AA: P=0.005, OR=1.71, 95%CI 1.18-2.48, P(heterogeneity)=0.99). In the subgroup analysis by ethnicity, significant association was also found among Han Chinese for both A-6G and A-20C polymorphisms. A borderline significantly decreased risk of hypertension between A-6G and Chinese Mongolian was seen in the allele comparison (A vs. G: P=0.05, OR=0.79, 95%CI 0.62-1.00, P(heterogeneity)=0.84). CONCLUSION: Our meta-analysis indicated significant association between angiotensinogen promoter polymorphisms and hypertension in the Chinese populations, especially in Han Chinese

Being oneself through time: bases of self-continuity across 55 cultures

Self-continuity – the sense that one’s past, present, and future are meaningfully connected – is considered a defining feature of personal identity. However, bases of self-continuity may depend on cultural beliefs about personhood. In multilevel analyses of data from 7287 adults from 55 cultural groups in 33 nations, we tested a new tripartite theoretical model of bases of self-continuity. As expected, perceptions of stability, sense of narrative, and associative links to one’s past each contributed to predicting the extent to which people derived a sense of self-continuity from different aspects of their identities. Ways of constructing self-continuity were moderated by cultural and individual differences in mutable (vs. immutable) personhood beliefs – the belief that human attributes are malleable. Individuals with lower mutability beliefs based self-continuity more on stability; members of cultures where mutability beliefs were higher based self-continuity more on narrative. Bases of self-continuity were also moderated by cultural variation in contextualized (vs. decontextualized) personhood beliefs, indicating a link to cultural individualism-collectivism. Our results illustrate the cultural flexibility of the motive for self-continuity