The receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis

PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of FGFR activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology

Generalised Compositional Theories and Diagrammatic Reasoning

This chapter provides an introduction to the use of diagrammatic language, or perhaps more accurately, diagrammatic calculus, in quantum information and quantum foundations. We illustrate the use of diagrammatic calculus in one particular case, namely the study of complementarity and non-locality, two fundamental concepts of quantum theory whose relationship we explore in later part of this chapter. The diagrammatic calculus that we are concerned with here is not merely an illustrative tool, but it has both (i) a conceptual physical backbone, which allows it to act as a foundation for diverse physical theories, and (ii) a genuine mathematical underpinning, permitting one to relate it to standard mathematical structures.Comment: To appear as a Springer book chapter chapter, edited by G. Chirabella, R. Spekken

The food choice at work study: effectiveness of complex workplace dietary interventions on dietary behaviours and diet-related disease risk - study protocol for a clustered controlled trial

Background: Dietary behaviour interventions have the potential to reduce diet-related disease. Ample opportunity exists to implement these interventions in the workplace. The overall aim is to assess the effectiveness and cost-effectiveness of complex dietary interventions focused on environmental dietary modification alone or in combination with nutrition education in large manufacturing workplace settings. Methods/design: A clustered controlled trial involving four large multinational manufacturing workplaces in Cork will be conducted. The complex intervention design has been developed using the Medical Research Council's framework and the National Institute for Health and Clinical Excellence (NICE) guidelines and will be reported using the TREND statement for the transparent reporting of evaluations with non-randomized designs. It will draw on a soft paternalistic 'nudge' theoretical perspective. It will draw on a soft paternalistic "nudge" theoretical perspective. Nutrition education will include three elements: group presentations, individual nutrition consultations and detailed nutrition information. Environmental dietary modification will consist of five elements: (a) restriction of fat, saturated fat, sugar and salt, (b) increase in fibre, fruit and vegetables, (c) price discounts for whole fresh fruit, (d) strategic positioning of healthier alternatives and (e) portion size control. No intervention will be offered in workplace A (control). Workplace B will receive nutrition education. Workplace C will receive nutrition education and environmental dietary modification. Workplace D will receive environmental dietary modification alone. A total of 448 participants aged 18 to 64 years will be selected randomly. All permanent, full-time employees, purchasing at least one main meal in the workplace daily, will be eligible. Changes in dietary behaviours, nutrition knowledge, health status with measurements obtained at baseline and at intervals of 3 to 4 months, 7 to 9 months and 13 to 16 months will be recorded. A process evaluation and cost-effectiveness economic evaluation will be undertaken. Discussion: A 'Food Choice at Work' toolbox (concise teaching kit to replicate the intervention) will be developed to inform and guide future researchers, workplace stakeholders, policy makers and the food industry. Trial registration: Current Controlled Trials, ISRCTN35108237

Inheritance of resistance to common bacterial blight in four selected common bean (\u3ci\u3ePhaseolus vulgaris\u3c/i\u3e L.) genotypes

Common bacterial blight (CBB) is the most serious bacterial disease of common bean in Uganda. It causes severe yield losses of up to 62%. Genetic resistance is the most effective option for controlling CBB in smallholder common bean production systems. This study was carried out to determine the inheritance pattern of CBB resistance in leaf and pod of four new resistance sources. The four resistant and four susceptible genotypes were crossed in a half-diallel mating design. F1 individuals were advanced to F2 and evaluated with the parents, in a randomized complete block design replicated twice. Combining ability analysis was performed according to Griffing\u27s (1956) method IV and model 1 using Genstat 12th. General combining ability effects were significant whereas specific combining ability was not suggesting that resistance to CBB in leaf and pod was primarily controlled by additive genes effects. The estimated narrow sense coefficient of genetic determination was moderately high (0.65) for the resistance in leaf and high (0.83) for resistance in pod suggesting that early-generation selection would be effective. Baker’s ratio estimates were relatively high for resistance in leaf (0.79) and pod (0.9) suggesting that hybrids’ performance can be predicted based on the parents’ general combining ability (GCA) effects

Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population.</p> <p>Methods/Design</p> <p>This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data).</p> <p>Discussion</p> <p>This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain.</p> <p>Trial Registration</p> <p>Current controlled trial ISRCTN54009836</p

Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis

Download PDFPDF Urology Protocol Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis Joseph M Norris1, Benjamin S Simpson1, Marina A Parry2, Clare Allen3, Rhys Ball4, Alex Freeman4, Daniel Kelly5, Alex Kirkham3, Veeru Kasivisvanathan1, Hayley C Whitaker1, Mark Emberton1 Author affiliations Abstract Introduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI. Methods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. Ethics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences

Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa.

OBJECTIVE: To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA). METHODS: Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later. RESULTS: Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77-10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11-20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14-12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23-8.54). CONCLUSION: HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37-90% of CIN2+ among African WLHIV

Cross-Sectional Associations of Total Daily Volume and Activity Patterns across the Activity Spectrum with Cardiometabolic Risk Factors in Children and Adolescents

Sedentary and physical activity patterns (bouts/breaks) may be important for cardiometabolic health in early life. This study aimed to examine cross-sectional associations of total daily volume and patterns across the activity spectrum with cardiometabolic risk factors in youth aged 7–13 years. Objectively measured accelerometer and cardiometabolic risk factor data were pooled from two studies (n = 1219; 69% valid accelerometry). Total daily volume of sedentary time and light-, moderate-, and vigorous-intensity physical activity was determined. Time in sustained bouts and median bout lengths of all intensities and breaks in sedentary time were also calculated. Outcomes included body mass index, waist circumference, blood pressure, blood lipids, and a cardiometabolic summary score. Regression models revealed beneficial associations between total daily volumes of moderate- and vigorous-intensity physical activity and cardiometabolic risk. Time spent in ≥1 min vigorous-intensity physical activity bouts was beneficially associated with cardiometabolic risk, yet this disappeared after adjusting for total vigorous-intensity physical activity and confounders. Time accumulated in light- (≥1 min; ≥5 min) and moderate-intensity (≥1 min) physical activity bouts was detrimentally associated with cardiometabolic risk. Total daily volume and activity patterns may have implications for cardiometabolic risk early in life. Sporadic physical activity may be more beneficial for health than sustained physical activity