Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy.

Increases in the number of cell therapies in the preclinical and clinical phases have prompted the need for reliable and non-invasive assays to validate transplant function in clinical biomanufacturing. We developed a robust characterization methodology composed of quantitative bright-field absorbance microscopy (QBAM) and deep neural networks (DNNs) to non-invasively predict tissue function and cellular donor identity. The methodology was validated using clinical-grade induced pluripotent stem cell derived retinal pigment epithelial cells (iPSC-RPE). QBAM images of iPSC-RPE were used to train DNNs that predicted iPSC-RPE monolayer transepithelial resistance, predicted polarized vascular endothelial growth factor (VEGF) secretion, and matched iPSC-RPE monolayers to the stem cell donors. DNN predictions were supplemented with traditional machine learning algorithms that identified shape and texture features of single cells that were used to predict tissue function and iPSC donor identity. These results demonstrate non-invasive cell therapy characterization can be achieved with QBAM and machine learning

Exact deterministic representation of Markovian SIR epidemics on networks with and without loops

In a previous paper Sharkey et al. (Bull Math Biol doi: 10.1007/s11538-013-9923-5, 2012) proved the exactness of closures at the level of triples for Markovian SIR (susceptible-infected-removed) dynamics on tree-like networks. This resulted in a deterministic representation of the epidemic dynamics on the network that can be numerically evaluated. In this paper, we extend this modelling framework to certain classes of networks exhibiting loops. We show that closures where the loops are kept intact are exact, and lead to a simplified and numerically solvable system of ODEs (ordinary-differential-equations). The findings of the paper lead us to a generalisation of closures that are based on partitioning the network around nodes that are cut-vertices (i.e. the removal of such a node leads to the network breaking down into at least two disjointed components or subnetworks). Exploiting this structural property of the network yields some natural closures, where the evolution of a particular state can typically be exactly given in terms of the corresponding or projected states on the subnetworks and the cut-vertex. A byproduct of this analysis is an alternative probabilistic proof of the exactness of the closures for tree-like networks presented in Sharkey et al. (Bull Math Biol doi: 10.1007/s11538-013-9923-5, 2012). In this paper we also elaborate on how the main result can be applied to more realistic networks, for which we write down the ODEs explicitly and compare output from these to results from simulation. Furthermore, we give a general, recipe-like method of how to apply the reduction by closures technique for arbitrary networks, and give an upper bound on the maximum number of equations needed for an exact representation

Approximation of the critical buckling factor for composite panels

This article is concerned with the approximation of the critical buckling factor for thin composite plates. A new method to improve the approximation of this critical factor is applied based on its behavior with respect to lamination parameters and loading conditions. This method allows accurate approximation of the critical buckling factor for non-orthotropic laminates under complex combined loadings (including shear loading). The influence of the stacking sequence and loading conditions is extensively studied as well as properties of the critical buckling factor behavior (e.g concavity over tensor D or out-of-plane lamination parameters). Moreover, the critical buckling factor is numerically shown to be piecewise linear for orthotropic laminates under combined loading whenever shear remains low and it is also shown to be piecewise continuous in the general case. Based on the numerically observed behavior, a new scheme for the approximation is applied that separates each buckling mode and builds linear, polynomial or rational regressions for each mode. Results of this approach and applications to structural optimization are presented

Weight loss referrals for adults in primary care (WRAP) : Protocol for a multi-centre randomised controlled trial comparing the clinical and cost-effectiveness of primary care referral to a commercial weight loss provider for 12 weeks, referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232]

Background: Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design. This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ≥28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, and blood pressure at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion. The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision

Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

BACKGROUND: Fas receptor-mediated eosinophil apoptosis is currently forwarded as a mechanism resolving asthma-like inflammation. This view is based on observations in vitro and in airway lumen with unknown translatability to airway tissues in vivo. In fact, apoptotic eosinophils have not been detected in human diseased airway tissues whereas cytolytic eosinophils abound and constitute a major mode of degranulation of these cells. Also, Fas receptor stimulation may bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells. We thus hypothesized that effects of anti-Fas mAb in vivo may include both apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic inflammation may not resolve by this treatment. METHODS: Weeklong daily allergen challenges of sensitized mice were followed by airway administration of anti-Fas mAb. BAL was performed and airway-pulmonary tissues were examined using light and electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus production and plasma exudation (fibrinogen) were performed. RESULTS: Anti-Fas mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in allergen-challenged airway tissues. Furthermore, a majority of the apoptotic eosinophils remained unengulfed and eventually exhibited secondary necrosis. A striking histopathology far beyond the allergic inflammation developed and included degranulated eosinophils, neutrophilia, epithelial derangement, plasma exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals without eosinophilia anti-Fas evoked no inflammatory response. CONCLUSION: An efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb evoked unprecedented asthma-like inflammation in mouse allergic airways. This outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic tissue eosinophils progressed into the pro-inflammatory cellular fate of secondary necrosis this may also explain the aggravated inflammation. Our data indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in vivo may cause severe disease exacerbation due to direct cytolysis and secondary necrosis of eosinophils

EZH2-mediated epigenetic repression of DNA repair in promoting breast tumor initiating cells

Members of the Polycomb-group (PcG) family of proteins, including EZH2 (enhancer of zeste homolog 2), are involved in establishing epigenetic silencing of developmental genes in adult and embryonic stem cells, and their deregulation has been implicated in cancer. In a recent report, EZH2-mediated epigenetic repression of DNA damage repair in breast tumor initiating cells (BTICs) was identified as a mechanism that could promote expansion of BTICs, and may contribute to cancer progression

Maternal anthropometric characteristics in pregnancy and blood pressure among adolescents: 1993 live birth cohort, Pelotas, southern Brazil

<p>Abstract</p> <p>Background</p> <p>We investigated the association between maternal anthropometric measurements in prepregnancy and at the end of pregnancy and their children's systolic (SBP) and diastolic (DBP) blood pressure at 11 years of age, in a prospective cohort study.</p> <p>Methods</p> <p>All hospital births which took place in 1993 in the city of Pelotas - Brazil, were identified (5,249 live births). In 2004, the overall proportion of follow-up was 85% and we obtained arterial blood pressure measurements of 4,452 adolescents.</p> <p>Results</p> <p>Independent variables analyzed included maternal prepregnancy weight and body mass index (BMI) and maternal weight, and height at the end of pregnancy. Multiple linear regression analysis controlling for the following confounders were carried out: adolescent's skin color, family income at birth, smoking, alcohol intake during pregnancy, and gestational arterial hypertension. Mean SBP and DBP were 101.9 mmHg (SD 12.3) and 63.4 mmHg (SD 9.9), respectively. Maternal prepregnancy weight and BMI, and weight at the end of pregnancy were positively associated with both SBP and DBP in adolescent subjects of both sexes; maternal height was positively associated with SBP only among males.</p> <p>Conclusions</p> <p>Adequate evaluation of maternal anthropometric characteristics during pregnancy may prevent high levels of blood pressure among adolescent children.</p

Crowding: risk factor or protective factor for lower respiratory disease in young children?

BACKGROUND: To study the effects of household crowding upon the respiratory health of young children living in the city of São Paulo, Brazil. METHODS: Case-control study with children aged from 2 to 59 months living within the boundaries of the city of São Paulo. Cases were children recruited from 5 public hospitals in central São Paulo with an acute episode of lower respiratory disease. Children were classified into the following diagnostic categories: acute bronchitis, acute bronchiolitis, pneumonia, asthma, post-bronchiolitis wheezing and wheezing of uncertain aetiology. One control, crudely matched to each case with regard to age (<2, 2 years old or more), was selected among healthy children living in the neighborhood of the case. All buildings were surveyed for the presence of environmental contaminants, type of construction and building material. Plans of all homes, including measurements of floor area, height of walls, windows and solar orientation, was performed. Data were analysed using conditional logistic regression. RESULTS: A total of 313 pairs of children were studied. Over 70% of the cases had a primary or an associated diagnosis of a wheezing illness. Compared with controls, cases tended to live in smaller houses with less adequate sewage disposal. Cases and controls were similar with respect to the number of people and the number of children under five living in the household, as well the number of people sharing the child's bedroom. After controlling for potential confounders, no evidence of an association between number of persons sharing the child's bedroom and lower respiratory disease was identified when all cases were compared with their controls. However, when two categories of cases were distinguished (infections, asthma) and each category compared separately with their controls, crowding appeared to be associated with a 60% reduction in the incidence of asthma but with 2 1/2-fold increase in the incidence of lower respiratory tract infections (p = 0.001). CONCLUSION: Our findings suggest that household crowding places young children at risk of acute lower respiratory infection but may protect against asthma. This result is consistent with the hygiene hypothesis

Periprosthetic osteolysis due to metastatic renal cell carcinoma: a case report

Failure of total hip arthroplasty through septic or aseptic loosening, periprosthetic fracture, or recurrent dislocation is well recognized and understood. We present an unusual cause of failure of total hip replacement which occurred on a 79 year old gentleman: that of prosthetic loosening secondary to malignant infiltration around components. Our aim is to highlight the fact that malignant infiltration should be considered as part of the differential diagnosis in aseptic and septic loosening of prosthetic implants

Comparison of face-to-face versus email guided self-help for binge eating: study protocol for a randomised controlled trial

Background Guided self-help is a recommended first-step treatment for bulimia nervosa, binge eating disorder and atypical variants of these disorders. Further research is needed to compare guided self-help that is delivered face-to-face versus via email. Methods/Design This clinical trial uses a randomised, controlled design to investigate the effectiveness of providing guided self-help either face-to-face or via e-mail, also using a delayed treatment control condition. At least 17 individuals are required per group, giving a minimum N of 51. Discussion Symptom outcomes will be assessed and estimates of cost-effectiveness made. Results are proposed to be disseminated locally and internationally (through submission to conferences and peer-reviewed journals), and will hopefully inform local service provision. The trial has been approved by an ethics review board and was registered with ClinicalTrials.gov NCT01832792 on 9 April 2013