Flower Dooms Cells to Death

In Drosophila imaginal discs, viable cells are outcompeted by their faster growing neighbors in a process called “cell competition.” A new study in this issue of Developmental Cell identifies the membrane protein Flower as being specifically induced in the outcompeted cells and required for their ensuing apoptosis

Protein degradation, signaling, microRNAs and cancer

A report on the biannual Swiss Institute for Experimental Cancer Research (ISREC) Symposium on the Cell and Molecular Biology of Cancer, Lausanne, Switzerland, 19-22 January 2005

A novel approach to evaluate the effect of medicaments used in endodontic regeneration on root canal surface indentation

Bone Biology Laboratory http://www.iupui.edu/~bonelab/ Department of Anatomy and Cell Biology Indiana University School of Medicine Department of Biomedical Engineering IUPUIObjectives: To investigate the capability of a novel reference point indentation apparatus to test the indentation properties of root canal surface dentine treated with three intracanal medicaments used in endodontic regeneration. Materials and Methods: Immature human premolars were selected (n=22). Four specimens were obtained from each root and randomly assigned to three treatment groups and a control group. Each specimen was exposed to one of three treatment pastes (triple antibiotic (TAP), double antibiotic (DAP), or calcium hydroxide [Ca(OH)2] or neutral de-ionized water (control) for one or four weeks. After each time-interval, the indentation properties of the root canal dentine surfaces were measured using a BioDent reference point indenter. Two-way ANOVA and Fisher’s Protected Least Significant Differences were used for statistical analyses. Results: Significant differences in indentation parameters and estimated hardness between all groups at both time points were found. TAP treated dentine had the highest significant indentation parameters, followed by DAP treated dentine, untreated control dentine and Ca(OH)2 treated dentine, respectively. Furthermore, TAP treated dentine had the lowest significant estimated hardness, followed by DAP treated dentine, untreated control dentine and Ca(OH)2 treated dentine, respectively. Conclusion: BioDent reference point indenter was able to detect significant differences in indentation properties of root canal dentine treated with various medicaments. Clinical Relevance: The use of a reference point indenter is a promising approach to characterize the indentation properties of root canal surfaces without any surface modification. This might provide an in vitro mechanical measurement that is more representative of the actual clinical situation

Correction to:A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics: a randomised controlled trial

Acknowledgements Our thanks to Elizabeth Banks who advised and assisted with many aspects of the study and also to the many women who commented on the development and design of this study including those on our Public Advisory Team (Pamela Deponio, Maggie Taylor and Mary Wotherspoon). Funding This work was supported by The Scottish Government, grant number BC/Screening/17/01. The funders provided independent referee reports which guided the final study design. The funders have read this manuscript. In-kind support was given by Breast Cancer Now for facilitating this study.Peer reviewedPublisher PD

A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics:a randomised controlled trial

Background: It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. Methods: A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). Results: Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS). Conclusions: A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk

Correction: Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 Infection

BACKGROUND: During acute and early HIV-1 infection (AEI), up to 60% of CD4(+) T cells in the lamina propria of the lower gastrointestinal (GI) tract are lost as early as 2–4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART) is well established. However, the extent of immune reconstitution in the GI tract is unknown. METHODS AND FINDINGS: Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1–7 y of uninterrupted therapy). Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%–60% depletion of lamina propria lymphocytes despite 1–7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO(+) HLA-DR(+), returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4(+) T cell depletion despite therapy. Rare HIV-1 RNA–expressing cells were detected by in situ hybridization. CONCLUSIONS: Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically silent over the short term, the long-term consequences of the persistence of this lesion may emerge as the HIV-1–infected population survives longer owing to the benefits of HAART

The effect of optimised patient information materials on recruitment in a lung cancer screening trial: an embedded randomised recruitment trial.

BACKGROUND: Written participant information materials are important for ensuring that potential trial participants receive necessary information so that they can provide informed consent. However, such materials are frequently long and complex, which may negatively impact patient understanding and willingness to participate. Improving readability, ease of comprehension and presentation may assist with improved participant recruitment. The Systematic Techniques for Assisting Recruitment to Trials (MRC START) study aimed to develop and evaluate interventions to improve trial recruitment. This study aimed to assess the effectiveness of an optimised participant information brochure and cover letter developed by MRC START regarding response and participant recruitment rates. METHODS: We conducted a study within a trial (SWAT) embedded in the EarlyCDT Lung Cancer Scotland (ECLS) trial that aimed to assess the effectiveness of a new test in reducing the incidence of patients with late-stage lung cancer at diagnosis compared with standard care. Potential participants approached for ECLS were randomised to receive the original participant information brochure and accompanying letter (control group) or optimised versions of these materials which had undergone user testing and a process of re-writing, re-organisation and professional graphic design (intervention group). The primary outcome was the number of patients recruited to ECLS. The secondary outcome was the proportion of patients expressing an interest in participating in ECLS. RESULTS: In total, 2262 patients were randomised, 1136 of whom were sent the intervention materials and 1126 of whom were sent the control materials. The proportion of patients enrolled and randomised into ECLS was 180 of 1136 (15.8%) in the intervention group and 176 of 1126 (15.6%) in the control group (OR = 1.016, 95% CI, 0.660 to 1.564). The proportion of patients who positively responded to the invitation was 224 of 1136 (19.7%) in the intervention group and 205 of 1126 (18.2%) in the control group (OR = 1.103, 95% CI, 0.778 to 1.565). CONCLUSIONS: Optimised patient information materials made little difference to the proportion of patients positively responding to a trial invitation or to the proportion subsequently randomised to the host trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925625 . Registered on 15 August 2015. Study Within A Trial, SWAT-23. Registered on 12 April 2016

Hospital readmission rates: signal of failure or success?

Hospital readmission rates are increasingly used as signals of hospital performance and a basis for hospital reimbursement. However, their interpretation may be complicated by differential patient survival rates. If patient characteristics are not perfectly observable and hospitals differ in their mortality rates, then hospitals with low mortality rates are likely to have a larger share of un-observably sicker patients at risk of a readmission. Their performance on readmissions will then be underestimated. We examine hospitals' performance relaxing the assumption of independence between mortality and readmissions implicitly adopted in many empirical applications. We use data from the Hospital Episode Statistics on emergency admissions for fractured hip in 290,000 patients aged 65 and over from 2003 to 2008 in England. We find evidence of sample selection bias that affects inference from traditional models. We use a bivariate sample selection model to allow for the selection process and the dichotomous nature of the outcome variables