"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

<p>Abstract</p> <p>Background</p> <p><it>MYG1 </it>(<it>Melanocyte proliferating gene 1</it>, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that <it>MYG1 </it>mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the <it>MYG1 </it>gene, to investigate their functionality, and to study their association with vitiligo susceptibility.</p> <p>Methods</p> <p>Nine single nucleotide polymorphisms (SNPs) in the <it>MYG1 </it>locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). <it>MYG1 </it>expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture.</p> <p>Results</p> <p>Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher <it>MYG1 </it>mRNA levels than controls with -119C allele (<it>P </it>= 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, <it>P </it>< 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% <it>versus </it>39.3%, <it>P </it>< 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database.</p> <p>Conclusions</p> <p>Our study demonstrated that both <it>MYG1 </it>promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the <it>MYG1 </it>gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo.</p

Host Factors Required for Modulation of Phagosome Biogenesis and Proliferation of Francisella tularensis within the Cytosol

Francisella tularensis is a highly infectious facultative intracellular bacterium that can be transmitted between mammals by arthropod vectors. Similar to many other intracellular bacteria that replicate within the cytosol, such as Listeria, Shigella, Burkholderia, and Rickettsia, the virulence of F. tularensis depends on its ability to modulate biogenesis of its phagosome and to escape into the host cell cytosol where it proliferates. Recent studies have identified the F. tularensis genes required for modulation of phagosome biogenesis and escape into the host cell cytosol within human and arthropod-derived cells. However, the arthropod and mammalian host factors required for intracellular proliferation of F. tularensis are not known. We have utilized a forward genetic approach employing genome-wide RNAi screen in Drosophila melanogaster-derived cells. Screening a library of ∼21,300 RNAi, we have identified at least 186 host factors required for intracellular bacterial proliferation. We silenced twelve mammalian homologues by RNAi in HEK293T cells and identified three conserved factors, the PI4 kinase PI4KCA, the ubiquitin hydrolase USP22, and the ubiquitin ligase CDC27, which are also required for replication in human cells. The PI4KCA and USP22 mammalian factors are not required for modulation of phagosome biogenesis or phagosomal escape but are required for proliferation within the cytosol. In contrast, the CDC27 ubiquitin ligase is required for evading lysosomal fusion and for phagosomal escape into the cytosol. Although F. tularensis interacts with the autophagy pathway during late stages of proliferation in mouse macrophages, this does not occur in human cells. Our data suggest that F. tularensis utilizes host ubiquitin turnover in distinct mechanisms during the phagosomal and cytosolic phases and phosphoinositide metabolism is essential for cytosolic proliferation of F. tularensis. Our data will facilitate deciphering molecular ecology, patho-adaptation of F. tularensis to the arthropod vector and its role in bacterial ecology and patho-evolution to infect mammals

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

RT-GENE: Real-time eye gaze estimation in natural environments

In this work, we consider the problem of robust gaze estimation in natural environments. Large camera-to-subject distances and high variations in head pose and eye gaze angles are common in such environments. This leads to two main shortfalls in state-of-the-art methods for gaze estimation: hindered ground truth gaze annotation and diminished gaze estimation accuracy as image resolution decreases with distance. We first record a novel dataset of varied gaze and head pose images in a natural environment, addressing the issue of ground truth annotation by measuring head pose using a motion capture system and eye gaze using mobile eyetracking glasses. We apply semantic image inpainting to the area covered by the glasses to bridge the gap between training and testing images by removing the obtrusiveness of the glasses. We also present a new real-time algorithm involving appearance-based deep convolutional neural networks with increased capacity to cope with the diverse images in the new dataset. Experiments with this network architecture are conducted on a number of diverse eye-gaze datasets including our own, and in cross dataset evaluations. We demonstrate state-of-the-art performance in terms of estimation accuracy in all experiments, and the architecture performs well even on lower resolution images

A computer-based medical record system and personal digital assistants to assess and follow patients with respiratory tract infections visiting a rural Kenyan health centre

BACKGROUND: Clinical research can be facilitated by the use of informatics tools. We used an existing electronic medical record (EMR) system and personal data assistants (PDAs) to assess the characteristics and outcomes of patients with acute respiratory illnesses (ARIs) visiting a Kenyan rural health center. METHODS: We modified the existing EMR to include details on patients with ARIs. The EMR database was then used to identify patients with ARIs who were prospectively followed up by a research assistant who rode a bicycle to patients' homes and entered data into a PDA. RESULTS: A total of 2986 clinic visits for 2009 adult patients with respiratory infections were registered in the database between August 2002 and January 2005; 433 patients were selected for outcome assessments. These patients were followed up in the villages and assessed at 7 and 30 days later. Complete follow-up data were obtained on 381 patients (88%) and merged with data from the enrollment visit's electronic medical records and subsequent health center visits to assess duration of illness and complications. Symptoms improved at 7 and 30 days, but a substantial minority of patients had persistent symptoms. Eleven percent of patients sought additional care for their respiratory infection. CONCLUSION: EMRs and PDA are useful tools for performing prospective clinical research in resource constrained developing countries

“Did I bring it on myself?” An exploratory study of the beliefs that adolescents referred to mental health services have about the causes of their depression

Background: The causal beliefs which adults have regarding their mental health difficulties have been linked to help-seeking behaviour, treatment preferences and the outcome of therapy; yet the topic remains a relatively unexplored one in the adolescent literature. Aims: This exploratory study aims to explore the causal beliefs regarding depression among a sample of clinically referred adolescents. Design: 77 adolescents, aged between 11 and 17, all diagnosed with moderate to severe depression, were interviewed using a semi-structured interview schedule, at the beginning of their participation in a randomised controlled trial. Data were analysed qualitatively using Framework Analysis. Findings: The study identified three themes related to causal beliefs: 1) Bewilderment about why they were depressed; 2) Depression as a result of rejection, victimisation and stress; and 3) Something inside is to blame. Conclusion: Although some adolescents struggled to identify the causes of their depression, many identified stressful life experiences as the cause of their current depression. They also tended to emphasise their own negative ways of interpreting those events, and some believed that their depression was caused by something inside them. Adolescents’ causal beliefs are likely to have implications for the way they seek help and engage in treatment, making it important to understand how adolescents understand their difficulties