Bias and Sensitivity Analysis When Estimating Treatment Effects from the Cox Model with Omitted Covariates

Omission of relevant covariates can lead to bias when estimating treatment or exposure effects from survival data in both randomized controlled trials and observational studies. This paper presents a general approach to assessing bias when covariates are omitted from the Cox model. The proposed method is applicable to both randomized and non‐randomized studies. We distinguish between the effects of three possible sources of bias: omission of a balanced covariate, data censoring and unmeasured confounding. Asymptotic formulae for determining the bias are derived from the large sample properties of the maximum likelihood estimator. A simulation study is used to demonstrate the validity of the bias formulae and to characterize the influence of the different sources of bias. It is shown that the bias converges to fixed limits as the effect of the omitted covariate increases, irrespective of the degree of confounding. The bias formulae are used as the basis for developing a new method of sensitivity analysis to assess the impact of omitted covariates on estimates of treatment or exposure effects. In simulation studies, the proposed method gave unbiased treatment estimates and confidence intervals with good coverage when the true sensitivity parameters were known. We describe application of the method to a randomized controlled trial and a non‐randomized study

Six of the scariest horror comics

First paragraph: Comic books of the 1950s and 1960s made a point of their potential to terrify, with anthologies from Entertaining Comics, such as Haunt of Fear, Vault of Horror, and Tales of the Crypt, boasting covers with straplines such as “Within these pages dwell creatures from the terrifying beyond!” The House of Mystery series from rival DC Comics asks: “Dare you enter the house of mystery?” – and cover art often depicts children or young adults on the cusp of discovering what lies within. This teasing investigation and revelation of horror has always been a key trope in horror comics – from their earliest days to the resurgence of interest in the format in recent decades. As darkness descends around Halloween, here are some of the most chilling reads the graphic novel medium has to offer.https://theconversation.com/six-of-the-scariest-horror-comics-10562

Child abuse registration, fetal growth, and preterm birth: a population based study

Objectives: To study the relation of intra-uterine growth and gestational age with child protection registration in a 20 year whole population birth cohort. Setting: West Sussex area of England. Study design: Retrospective whole population birth cohort. Outcomes: Child protection registration; individual categories of registration—sexual abuse, physical abuse, emotional abuse, and neglect. Population and participants: 119 771 infants born in West Sussex between January 1983 and December 2001 with complete data including birth weight, gestational age, maternal age, and postcode. Results: In all categories of registration a linear trend was noted such that the lower the birth weight z score the higher the likelihood of child protection registration. Similar trends were noted for gestational age. All these trends were robust to adjustment for maternal age and socioeconomic status. Conclusions: The results of this study suggest that lower levels of fetal growth and shorter gestational duration are associated with increased likelihood of child protection registration in all categories including sexual abuse independent of maternal age or socioeconomic status. This study does not permit comment on whether poor fetal growth or preterm birth predispose to child abuse and neglect or the association arises because they share a common pathway

Child and adolescent mental health trajectories in relation to exclusion from school from the Avon Longitudinal Study of Parents and Children

Background: As the prevalence of childhood mental health conditions varies by age and gender, we explored whether there were similar variations in the relationship between psychopathology and exclusion from school in a prospective UK population-based birth cohort. Method: The Avon Longitudinal Study of Parents and Children collected reports of exclusion at 8 years and 16 years. Mental health was assessed at repeated time points using the Strengths and Difficulties Questionnaire (SDQ). Results: Using adjusted linear mixed effects models, we detected a nonlinear interaction between exclusion and age related to poor mental health for boys [adjusted coefficient 1.13 (95% confidence interval 0.55-1.71)] excluded by age 8, but not for girls. The SDQ scores of boys who were excluded in primary school were higher than their peers from age 3, and increasingly diverged over time. As teenagers, these interactions appeared for both genders [boys' adjusted coefficient 0.18 (0.10-0.27); girls 0.29 (0.17-0.40)]. For teenage girls, exclusion by 16 was followed by deteriorating mental health. Family adversity predicted exclusion in all analyses. Conclusion: Prompt access to effective intervention for children in poor mental health may improve both mental health and access to education. Key practitioner message: Children who were subsequently excluded from school often faced family adversity and had poor mental health, which suggests the need for an interdisciplinary response and a multiagency approach. Poor mental health may contribute to and result from exclusion from school, so both mental health and education practitioners have a key role to play. Boys who enter school with poor mental health are at high risk of exclusion in primary school, which prompt assessment and intervention may prevent. Both boys and girls who are excluded between the ages of 15 and 16 years may have poor, and in the case of girls, deteriorating, mental health.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.UK Medical Research Council and Wellcome Trust. Grant Number: 092731published version, accepted version (12 month embargo), submitted versio

The development, feasibility and acceptability of a school-based obesity prevention programme: results from three phases of piloting

addresses: Institute for Health Service Research, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.notes: PMCID: PMC3191390types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2011 by the BMJ Publishing Group Ltd. This articles was first published in: BMJ, 2011, Vol. 1, Issue 1, pp. e000026 -To develop a school-based obesity prevention programme and evaluate the feasibility and acceptability of the intervention and the planned definitive cluster randomised trial

Nuair a bha Gaidhlig aig na h-eoin : an investigation into the art and artifice of avifaunal mimesis as a mode of artistic expression in Gaelic oral culture from the seventeenth century to the present

This investigation will interrogate the mimetic faculty of modern Gaelic oral culture, focussing particularly on mimesis as an artistic device. The imitation of nature in Gaelic is perhaps most frequently associated with the folk-song tradition, in which non-lexical vocable refrains are frequently deployed for the purposes of emulating a particular sound quality pertinent to an individual species or natural phenomenon, such as the call of the seal or the breaking of waves. The most common of these, however, imitate birds. For the purposes of this analysis, imitation is understood to mean both the acoustic replication of a primary sound object (in this instance birdsong) or alternatively the figurative imitation of a given image implied by the use of metaphor. To this end, the present study will be divided into three sections, delineated in terms of genre. Chapters one and three will address the faculty of acoustic bird imitation, the former focusing on the sonance and semantics of mimetic children’s rhymes and the latter examining the use of voice in dialogue segments attributed to birds in traditional Gaelic storytelling. In addition, the second chapter will look at the bird metaphor and its deployment as a vehicle for both praise and vilification in Gaelic poetry, interrogating the semiotic meanings such associations invoke. In summation, it will be argued that the imitation of birds in Gaelic oral culture can be read in a wider context as a form of artistic escapism ‘in which the ordinary features of our world are brought into focus by a certain exaggeration … a framing of reality that announces that what is contained within the frame is not simply real’ (Davis, 1999: 3)

The Effect of Light Intensity, Sensor Height, and Spectral Pre-Processing Methods When Using NIR Spectroscopy to Identify Different Allergen-Containing Powdered Foods

Food allergens present a significant health risk to the human population, so their presence must be monitored and controlled within food production environments. This is especially important for powdered food, which can contain nearly all known food allergens. Manufacturing is experiencing the fourth industrial revolution (Industry 4.0), which is the use of digital technologies, such as sensors, Internet of Things (IoT), artificial intelligence, and cloud computing, to improve the productivity, efficiency, and safety of manufacturing processes. This work studied the potential of small low-cost sensors and machine learning to identify different powdered foods which naturally contain allergens. The research utilised a near-infrared (NIR) sensor and measurements were performed on over 50 different powdered food materials. This work focussed on several measurement and data processing parameters, which must be determined when using these sensors. These included sensor light intensity, height between sensor and food sample, and the most suitable spectra pre-processing method. It was found that the K-nearest neighbour and linear discriminant analysis machine learning methods had the highest classification prediction accuracy for identifying samples containing allergens of all methods studied. The height between the sensor and the sample had a greater effect than the sensor light intensity and the classification models performed much better when the sensor was positioned closer to the sample with the highest light intensity. The spectra pre-processing methods, which had the largest positive impact on the classification prediction accuracy, were the standard normal variate (SNV) and multiplicative scattering correction (MSC) methods. It was found that with the optimal combination of sensor height, light intensity, and spectra pre-processing, a classification prediction accuracy of 100% could be achieved, making the technique suitable for use within production environments

Evidence, theory and context - using intervention mapping to develop a school-based intervention to prevent obesity in children

© 2011 Lloyd et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Only limited data are available on the development and feasibility piloting of school-based interventions to prevent and reduce obesity in children. Clear documentation of the rationale, process of development and content of such interventions is essential to enable other researchers to understand why interventions succeed or fail

Systematic review and meta-analysis of the association between childhood overweight and obesity and primary school diet and physical activity policies

AJW is funded by a Medical Research Council Doctoral Training Grant and Sport and Health Sciences, University of Exeter. SL, KMW, WEH and AJH are partially supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula.Obesity is a major public health concern and there are increasing calls for policy intervention. As obesity and the related health conditions develop during childhood, schools are being seen as important locations for obesity prevention, including multifaceted interventions incorporating policy elements. The objective of this systematic review was to evaluate the effects of policies related to diet and physical activity in schools, either alone, or as part of an intervention programme on the weight status of children aged 4 to 11 years. A comprehensive and systematic search of medical, education, exercise science, and social science databases identified 21 studies which met the inclusion criteria. There were no date, location or language restrictions. The identified studies evaluated a range of either, or both, diet and physical activity related policies, or intervention programmes including such policies, using a variety of observational and experimental designs. The policies were clustered into those which sought to affect diet, those which sought to affect physical activity and those which sought to affect both diet and physical activity to undertake random effects meta-analysis. Within the diet cluster, studies of the United States of America National School Lunch and School Breakfast Programs were analysed separately; however there was significant heterogeneity in the pooled results. The pooled effects of the physical activity, and other diet related policies on BMI-SDS were non-significant. The multifaceted interventions tended to include policy elements related to both diet and physical activity (combined cluster), and although these interventions were too varied to pool their results, significant reductions in weight-related outcomes were demonstrated. The evidence from this review suggests that, when implemented alone, school diet and physical activity related policies appear insufficient to prevent or treat overweight or obesity in children, however, they do appear to have an effect when developed and implemented as part of a more extensive intervention programme. Additional evidence is required before recommendations regarding the focus of policies can be made and therefore, increased effort should be made to evaluate the effect of policies and policy containing intervention programmes upon weight status.Publisher PDFPeer reviewe

Regional Morphogenesis in the Hypothalamus: A BMP-Tbx2 Pathway Coordinates Fate and Proliferation through Shh Downregulation

SummaryA central challenge in embryonic development is to understand how growth and pattern are coordinated to direct emerging new territories during morphogenesis. Here, we report on a signaling cascade that links cell proliferation and fate, promoting formation of a distinct progenitor domain within the developing chick hypothalamus. We show that the downregulation of Shh in floor plate-like cells in the forebrain governs their progression to a distinctive, proliferating hypothalamic progenitor domain. Shh downregulation occurs via a local BMP-Tbx2 pathway, Tbx2 acting to repress Shh expression. We show in vivo and in vitro that forced maintenance of Shh in hypothalamic progenitors prevents their normal morphogenesis, leading to maintenance of the Shh receptor, ptc, and preventing progression to an Emx2+-proliferative progenitor state. Our data identify a molecular pathway for the downregulation of Shh via a BMP-Tbx2 pathway and provide a mechanism for expansion of a discrete progenitor domain within the developing forebrain