echinus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases

Background: Programmed cell death is used to remove excess cells between ommatidia in the Drosophila pupal retina. This death is required to establish the crystalline, hexagonal packing of ommatidia that characterizes the adult fly eye. In previously described echinus mutants, interommatidial cell sorting, which precedes cell death, occurred relatively normally. Interommatidial cell death was partially suppressed, resulting in adult eyes that contained excess pigment cells, and in which ommatidia were mildly disordered. These results have suggested that echinus functions in the pupal retina primarily to promote interommatidial cell death. Results: We generated a number of new echinus alleles, some of which are likely null mutants. Analysis of these alleles provides evidence that echinus has roles in cell sorting as well as cell death. echinus encodes a protein with homology to ubiquitin-specific proteases, which cleave ubiquitin-conjugated proteins at the ubiquitin C-terminus. The echinus locus encodes multiple splice forms, including two proteins that lack residues thought to be critical for deubiquitination activity. Surprisingly, ubiquitous expression in the eye of versions of Echinus that lack residues critical for ubiquitin specific protease activity, as well as a version predicted to be functional, rescue the echinus loss-of-function phenotype. Finally, genetic interactions were not detected between echinus loss and gain-of-function and a number of known apoptotic regulators. These include Notch, EGFR, the caspases Dronc, Drice, Dcp-1, Dream, the caspase activators, Rpr, Hid, and Grim, the caspase inhibitor DIAP1, and Lozenge or Klumpfuss. Conclusions: The echinus locus encodes multiple splice forms of a protein with homology to ubiquitin-specific proteases, but protease activity is unlikely to be required for echinus function, at least when echinus is overexpressed. Characterization of likely echinus null alleles and genetic interactions suggests that echinus acts at a novel point(s) to regulate interommatidial cell sorting and/or cell death in the fly eye

Facilitating children's self-concept: A rationale and evaluative study

This study reports on the design and effectiveness of the Exploring Self-Concept program for primary school children using self-concept as the outcome measure. The program aims to provide a procedure that incorporates organisation, elaboration, thinking, and problem-solving strategies and links these to children's multidimensional self-concept. The results of this research support the notion that teachers and guidance counsellors need to establish a nonthreatening framework that allows them to discuss with children a range of relevant issues related to peer pressure, parent relations, self-image, body image, gender bias, media pressure, values and life goals, in a systematic, objective and cooperative manner. Within the paper, notions associated with self-concept maturation, 'crystallisation' of self-concept beliefs, cognitive differentiation and self-concept segmentation are reviewed

Ketamine as the anaesthetic for electroconvulsive therapy:the KANECT randomised controlled trial

C.AS. reports grants from Vifor Pharma, outside the submitted work. I.C.R. (deceased) declared personal fees from AstraZeneca, Sanofi Aventis and Sunovion, and non-financial support from Lundbeck, between 2009 and 2014 and all outside the submitted work. Volume 212, Issue 5 May 2018 , p. 323 Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial – CORRIGENDUM Gordon Fernie, James Currie, Jennifer S. Perrin, Caroline A. Stewart... https://doi.org/10.1192/bjp.2018.76 Published online: 06 April 2018 Summary: This notice describes a correction to the above mentioned paper.Peer reviewedPublisher PD

Recruitment of young women to a trial of chlamydia screening – as easy as it sounds?

BACKGROUND: Recruiting to trials is complex and difficult. The Prevention of Pelvic Infection (POPI) trial aims to see if screening women for chlamydia and treating those found to be infected reduces the incidence of pelvic inflammatory disease in the following twelve months. It focuses on young, sexually active, multiethnic, mainly inner city, female students. The main aim of this paper is to describe our recruitment methods. Secondary aims in two small subgroups, are to compare characteristics of women recruited with those not recruited, and to explore participants' understanding of when their samples would be tested for chlamydia. METHODS: Women students attending lectures or in common rooms at 22 universities and further education colleges were recruited by female research assistants working in pairs. Participants were asked to complete a questionnaire on sexual health and to provide self-taken vaginal swabs. In addition, during 3 recruitment sessions, a female medical student asked non-participants to complete a brief anonymous questionnaire on reasons for not taking part. Finally another female medical student contacted 40 consecutive participants within a month of recruitment and asked if they understood that their samples might not be tested for a year. RESULTS: With enormous effort over 2 years we recruited 2526 women. A survey of 61 non-responders showed only 18 (30%) were eligible to take part (age <28, been sexually active and not been tested for chlamydia in the past 3 months). Eligible non-responders were of similar age to the 35 responders in the same recruitment sessions, but more likely to be from ethnic minority groups (67% 12/18 versus 29% 10/35 p < 0.01). Email and telephone contact with 35/40 (88%) of consecutive participants showed only two (6%) did not understand that their specimen might not be tested for chlamydia for a year. Thirty participants (85%) could name one or more possible consequences of untreated chlamydia infection. CONCLUSION: As in other studies, a key to attaining recruitment targets was the enthusiasm of the research team. Minority ethnic groups were probably under-represented, but understanding of participants was good

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Baseline spatial distribution of malaria prior to an elimination programme in Vanuatu

BACKGROUND: The Ministry of Health in the Republic of Vanuatu has implemented a malaria elimination programme in Tafea Province, the most southern and eastern limit of malaria transmission in the South West Pacific. Tafea Province is comprised of five islands with malaria elimination achieved on one of these islands (Aneityum) in 1998. The current study aimed to establish the baseline distribution of malaria on the most malarious of the province's islands, Tanna Island, to guide the implementation of elimination activities. METHODS: A parasitological survey was conducted in Tafea Province in 2008. On Tanna Island there were 4,716 participants from 220 villages, geo-referenced using a global position system. Spatial autocorrelation in observed prevalence values was assessed using a semivariogram. Backwards step-wise regression analysis was conducted to determine the inclusion of environmental and climatic variables into a prediction model. The Bayesian geostatistical logistic regression model was used to predict malaria risk, and associated uncertainty across the island. RESULTS: Overall, prevalence on Tanna was 1.0% for Plasmodium falciparum (accounting for 32% of infections) and 2.2% for Plasmodium vivax (accounting for 68% of infections). Regression analysis showed significant association with elevation and distance to coastline for P. vivax and P. falciparum, but no significant association with NDVI or TIR. Colinearity was observed between elevation and distance to coastline with the later variable included in the final Bayesian geostatistical model for P. vivax and the former included in the final model for P. falciparum. Model validation statistics revealed that the final Bayesian geostatistical model had good predictive ability. CONCLUSION: Malaria in Tanna Island, Vanuatu, has a focal and predominantly coastal distribution. As Vanuatu refines its elimination strategy, malaria risk maps represent an invaluable resource in the strategic planning of all levels of malaria interventions for the island

Evaluating the effectiveness of a schools-based programme to promote exercise self-efficacy in children and young people with risk factors for obesity: Steps to active kids (STAK)

<p>Abstract</p> <p>Background</p> <p>Low levels of physical activity in children have been linked to an increased risk of obesity, but many children lack confidence in relation to exercise (exercise self-efficacy). Factors which can impact on confidence include a chronic health condition such as asthma, poor motor skills and being overweight. Increasing levels of physical activity have obvious benefits for children with asthma and children who are overweight, but few activity interventions with children specifically target children with low exercise self-efficacy (ESE). This study aims to evaluate the efficacy and feasibility of a schools-based activity programme suitable for children with risk factors for adult obesity, including asthma, overweight and low exercise self-efficacy.</p> <p>Methods/Design</p> <p>A clustered (at the level of school) RCT will be used to compare a targeted, 10 week, stepped activity programme (activity diary, dance DVD, circuit-training and motivational interviewing) designed to promote ESE. We will recruit 20 primary schools to participate in the intervention and 9-11 year old children will be screened for low levels of ESE, asthma and overweight. In order to provide sufficient power to detect a difference in primary outcomes (Body Mass Index-BMI & ESE at 12 month follow-up) between children in the intervention schools and control schools, the target sample size is 396. Assessments of BMI, ESE, waist circumference, peak flow, activity levels and emotional and behavioural difficulties will be made at baseline, 4 months and 12 month follow-up.</p> <p>Discussion</p> <p>We aim to increase ESE and levels of physical activity in children with risk factors for adult obesity. The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted health interventions within a school setting.</p> <p>Trial Registration</p> <p>ISRCTN Register no. <a href="http://www.controlled-trials.com/ISRCTN12650001">ISRCTN12650001</a></p

Effectiveness of Denitrifying Bioreactors on Water Pollutant Reduction from Agricultural Areas

HighlightsDenitrifying woodchip bioreactors treat nitrate-N in a variety of applications and geographies.This review focuses on subsurface drainage bioreactors and bed-style designs (including in-ditch).Monitoring and reporting recommendations are provided to advance bioreactor science and engineering. Denitrifying bioreactors enhance the natural process of denitrification in a practical way to treat nitrate-nitrogen (N) in a variety of N-laden water matrices. The design and construction of bioreactors for treatment of subsurface drainage in the U.S. is guided by USDA-NRCS Conservation Practice Standard 605. This review consolidates the state of the science for denitrifying bioreactors using case studies from across the globe with an emphasis on full-size bioreactor nitrate-N removal and cost-effectiveness. The focus is on bed-style bioreactors (including in-ditch modifications), although there is mention of denitrifying walls, which broaden the applicability of bioreactor technology in some areas. Subsurface drainage denitrifying bioreactors have been assessed as removing 20% to 40% of annual nitrate-N loss in the Midwest, and an evaluation across the peer-reviewed literature published over the past three years showed that bioreactors around the world have been generally consistent with that (N load reduction median: 46%; mean ±SD: 40% ±26%; n = 15). Reported N removal rates were on the order of 5.1 g N m-3 d-1 (median; mean ±SD: 7.2 ±9.6 g N m-3 d-1; n = 27). Subsurface drainage bioreactor installation costs have ranged from less than $5,000 to$27,000, with estimated cost efficiencies ranging from less than $2.50 kg-1 N year-1 to roughly$20 kg-1 N year-1 (although they can be as high as $48 kg-1 N year-1). A suggested monitoring setup is described primarily for the context of conservation practitioners and watershed groups for assessing annual nitrate-N load removal performance of subsurface drainage denitrifying bioreactors. Recommended minimum reporting measures for assessing and comparing annual N removal performance include: bioreactor dimensions and installation date; fill media size, porosity, and type; nitrate-N concentrations and water temperatures; bioreactor flow treatment details; basic drainage system and bioreactor design characteristics; and N removal rate and efficiency

TCR-stimulated changes in cell surface CD46 expression generate type 1 regulatory T cells

International audienc

Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development

Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cellular systems, and show that the developmental dynamics of 5-hmC are different from those of 5-methylcytosine (5-mC); in particular 5-hmC is enriched in embryonic contexts compared to adult tissues. A detectable 5-hmC signal appears in pre-implantation development starting at the zygote stage, where the paternal genome is subjected to a genome-wide hydroxylation of 5-mC, which precisely coincides with the loss of the 5-mC signal in the paternal pronucleus. Levels of 5-hmC are high in cells of the inner cell mass in blastocysts, and the modification colocalises with nestin-expressing cell populations in mouse post-implantation embryos. Compared to other adult mammalian organs, 5-hmC is strongly enriched in bone marrow and brain, wherein high 5-hmC content is a feature of both neuronal progenitors and post-mitotic neurons. We show that high levels of 5-hmC are not only present in mouse and human embryonic stem cells (ESCs) and lost during differentiation, as has been reported previously, but also reappear during the generation of induced pluripotent stem cells; thus 5-hmC enrichment correlates with a pluripotent cell state. Our findings suggest that apart from the cells of neuronal lineages, high levels of genomic 5-hmC are an epigenetic feature of embryonic cell populations and cellular pluri- and multi-lineage potency. To our knowledge, 5-hmC represents the first epigenetic modification of DNA discovered whose enrichment is so cell-type specific