Home interventions and light therapy for treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomized controlled trial

Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high quality evidence to inform clinical care. We describe here a large, independent, randomised controlled trial (RCT) assessing the comparative effectiveness of potent topical corticosteroid, home-based hand-held narrowband ultraviolet B-light (NB-UVB) or combination of the two, for the management of vitiligo. Methods and Analysis The HI-Light Vitiligo Trial is a multi-centre, three-arm, parallel group, pragmatic, placebo-controlled RCT. 516 adults and children with actively spreading, but limited, vitiligo are randomised (1:1:1) to one of three groups: mometasone furoate 0.1% ointment plus dummy NB-UVB light, vehicle ointment plus NB-UVB light, or mometasone furoate 0.1% ointment plus NB-UVB light. Treatment of up to three patches of vitiligo is continued for up to 9 months with clinic visits at baseline, 3, 6 and 9 months and four post treatment questionnaires. The HI-Light Vitiligo Trial assesses outcomes included in the vitiligo core outcome set and places emphasis on participants’ views of treatment success. The primary outcome is proportion of participants achieving treatment success (patient-rated Vitiligo Noticeability Scale) for a target patch of vitiligo at 9 months with further independent blinded assessment using digital images of the target lesion before and after treatment. Secondary outcomes include time to onset of treatment response, treatment success by body region, percentage repigmentation, quality of life, time-burden of treatment, maintenance of response, safety, and within-trial cost effectiveness. Ethics and Dissemination Approvals were granted by East Midlands–Derby Research Ethics Committee (14/EM/1173) and the MHRA (EudraCT 2014-003473-42). The trial was registered 8th January 2015 ISRCTN (17160087). Results will be published in full as open access in the NIHR Journal library and elsewhere

The October 2012 magnitude (Mw) 7.8 earthquake offshore Haida Gwaii, Canada

Alison L. Bird et al. report on the Mw 7.8 earthquake offshore Haida Gwaii, Canada, from 2012 for the Summary of the Bulletin of the International Seismological Centre

FORG3D: Force-directed 3D graph editor for visualization of integrated genome scale data

<p>Abstract</p> <p>Background</p> <p>Genomics research produces vast amounts of experimental data that needs to be integrated in order to understand, model, and interpret the underlying biological phenomena. Interpreting these large and complex data sets is challenging and different visualization methods are needed to help produce knowledge from the data.</p> <p>Results</p> <p>To help researchers to visualize and interpret integrated genomics data, we present a novel visualization method and bioinformatics software tool called FORG3D that is based on real-time three-dimensional force-directed graphs. FORG3D can be used to visualize integrated networks of genome scale data such as interactions between genes or gene products, signaling transduction, metabolic pathways, functional interactions and evolutionary relationships. Furthermore, we demonstrate its utility by exploring gene network relationships using integrated data sets from a <it>Caenorhabditis elegans </it>Parkinson's disease model.</p> <p>Conclusion</p> <p>We have created an open source software tool called FORG3D that can be used for visualizing and exploring integrated genome scale data.</p

Indicated Truancy Interventions: Effects on School Attendance Among Chronic Truant Students.

BACKGROUNDTruancy is a significant problem in the U.S. and in other countries around the world. Truancy has been linked to serious immediate and far-reaching consequences for youth, families, and schools and communities, leading researchers, practitioners, and policy makers to try to understand and to address the problem. Although numerous and significant steps have been taken at the local, state, and national levels to reduce truancy, the rates of truancy have at best remained stable or at worst been on the rise, depending on the indicator utilized to assess truancy rates. The costs and impact of chronic truancy are significant, with both short- and long-term implications for the truant youth as well as for the family, school, and community. Although several narrative reviews and one meta-analysis of attendance and truancy interventions have attempted to summarize the extant research, there are a number of limitations to these reviews. It is imperative that we systematically synthesize and examine the evidence base to provide a comprehensive picture of interventions that are being utilized to intervene with chronic truants, to identify interventions that are effective and ineffective, and to identify gaps and areas in which more research needs to be conducted to better inform practice and policy.OBJECTIVESThe main objective of this systematic review was to examine the effects of interventions on school attendance to inform policy, practice, and research. The questions guiding this study were: 1) Do truancy programs with a goal of increasing student attendance for truant youth affect school attendance behaviors of elementary and secondary students with chronic attendance problems?2) Are there differences in the effects of school-based, clinic/community-based, and court-based programs?3) Are some modalities (i.e., family, group, multimodal) more effective than others in increasing student attendance? SEARCH STRATEGYA systematic and comprehensive search process was employed to locate all possible studies between 1990 and 2009, with every effort made to include both published and unpublished studies to minimize publication bias. A wide range of electronic bibliographic databases and research registers was searched, websites of relevant research centers and groups were mined for possible reports, over 200 e-mails and letters were sent to programs listed in large databases of truancy programs compiled by the National Center for School Engagement and the National Dropout Prevention Center, and contact with researchers in the field of truancy and absenteeism was attempted. In addition, we examined reference lists of all previous reviews as well as citations in research reports for potential studies.SELECTION CRITERIAStudies eligible for this review were required to meet several eligibility criteria. Studies must have utilized a randomized, quasi-experimental, or single-group pre-posttest design with the aim of evaluating the effectiveness of interventions with a stated primary goal of increasing student attendance (or decreasing absenteeism) among chronic truant students. Studies must have measured an attendance outcome and reported sufficient data to calculate an effect size. Finally, studies must have been published between 1990 and 2009 in the United States, United Kingdom, Australia, or Canada. DATA COLLECTION AND ANALYSISA total of 28 studies, reported in 26 reports, met final eligibility criteria and were included in this review and meta-analysis. Of the studies that were included, 5 utilized a randomized design (RCT), 11 utilized a quasi-experimental design (QED), and 12 utilized a single group pre-posttest design (SGPP). All eligible studies were coded using a structured coding instrument, with 20% of studies coded by a second coder. Descriptive analysis was conducted to examine and describe data related to the characteristics of the included studies. Analysis of the mean effect size, the heterogeneity of effect sizes, and the relationship between effect size and methodological and substantive characteristics of the interventions was also conducted separately for the RCT/QED studies and the SGPP studies. The effect sizes were calculated using the standardized mean difference effect size statistic, correcting for small sample size using Hedges’ g (Hedges, 1992). Assuming a mixed effects model, the analog to the ANOVA and bivariate meta-regression frameworks were used to examine potential moderating variables related to study, participant, and intervention characteristics. RESULTSThe meta-analytic findings demonstrated a significant overall positive and moderate mean effect of interventions on attendance outcomes. The mean effect size for interventions examined in the included RCT studies was .57 and the mean effect size for the QED studies was .43. No significant differences were observed between the RCT and QED studies in the magnitude of the treatment effect (Qb= .28, p \u3e.05). The mean effect size of interventions examined using an SGPP design was .95. A moderate effect on attendance outcomes is encouraging; however, the overall mean effect size is masked by a large amount of heterogeneity, indicating significant variance in effect sizes between studies. Moderator analyses found no significant differences in mean effects between studies on any moderating variable tested. No differences were found between school-, court-, or community-based programs or between different modalities of programs. The duration of the intervention also did not demonstrate any association with effect size. Collaborative programs and multimodal interventions produced statistically similar effects on attendance as non-collaborative and single-modality programs, which runs counter to the prevailing beliefs and recommendations for best practices in truancy reduction found in the literature.Other significant findings from this study relate to methodological shortcomings, the absence of important variables as well as gaps in the evidence base. These findings include the lack of inclusion of minority students and a lack of reporting and statistical analysis of demographic variables, particularly race/ethnicity and socioeconomic status (SES). Given that race and SES have been linked to absenteeism, the absence of this data was surprising. The majority of studies also lacked adequate descriptions of the interventions, making replication of the intervention difficult, and failed to measure and report long-term outcomes. AUTHORS’ CONCLUSIONSOverall, the findings from this study suggest that chronic truant students benefit from interventions targeting attendance behaviors; thus it is important and worthwhile to intervene with chronic truant youth. Given the minimal differences in effects across program types and modalities, no one program type or modality stands out as being more effective than any other. Although no statistically significant differences in effects were found between types and modalities of interventions included in this review, there was a lack of available evidence to support the general belief (and popular “best-practice” recommendations) that collaborative and multimodal interventions are more effective than programs that are not collaborative and single modal interventions. Due to the small sample size and large heterogeneity between studies and within groups of studies, caution must be used when interpreting and applying the findings from this meta-analysis. Overall, the studies included in the review improved attendance by an average of 4.69 days, almost a full school week. However, although the interventions included in this study were, overall, found to be effective, the mean rates of absenteeism at posttest in most studies remained above acceptable levels. This finding indicates the need for additional work and research. Developing more effective interventions and policies as well as studying outcomes of interventions, particularly with vulnerable and at-risk populations, is crucial to combating absenteeism. The gaps and deficiencies identified in this study also affirm the need for increasing and strengthening the evidence base on which current policies and practices rest. Although additional outcome research is necessary, more of the same is not sufficient. Significant improvements in the quality of truancy intervention research are required and identified gaps need to be addressed. Recommendations to improve the quality and fill gaps in truancy intervention research are discussed here. In addition, given the significant and pervasive deficiencies in the extant research, a critical analysis of the practices, assumptions, and sociopolitical contexts underlying truancy intervention research seems warranted

Altered Immune Responses in Rhesus Macaques Co-Infected with SIV and Plasmodium cynomolgi: An Animal Model for Coincident AIDS and Relapsing Malaria

BACKGROUND:Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens. METHODOLOGY/PRINCIPAL FINDINGS:Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response. CONCLUSIONS/SIGNIFICANCE:These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions

Hidden in the Middle : Culture, Value and Reward in Bioinformatics

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether

Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease

One of the long-term goals of mutagenesis programs in the mouse has been to generate mutant lines to facilitate the functional study of every mammalian gene. With a combination of complementary genetic approaches and advances in technology, this aim is slowly becoming a reality. One of the most important features of this strategy is the ability to identify and compare a number of mutations in the same gene, an allelic series. With the advent of gene-driven screening of mutant archives, the search for a specific series of interest is now a practical option. This review focuses on the analysis of multiple mutations from chemical mutagenesis projects in a wide variety of genes and the valuable functional information that has been obtained from these studies. Although gene knockouts and transgenics will continue to be an important resource to ascertain gene function, with a significant proportion of human diseases caused by point mutations, identifying an allelic series is becoming an equally efficient route to generating clinically relevant and functionally important mouse models

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT

BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n =  119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field