The effects of arousal on apical amplification and conscious state

Neocortical pyramidal cells can integrate two classes of input separately and use one to modulate response to the other. Their tuft dendrites are electrotonically separated from basal dendrites and soma by the apical dendrite, and apical hyperpolarization-activated currents (Ih) further isolate subthreshold integration of tuft inputs. When apical depolarization exceeds a threshold, however, it can enhance response to the basal inputs that specify the cell’s selective sensitivity. This process is referred to as apical amplification (AA). We review evidence suggesting that, by regulating Ihin the apical compartments, adrenergic arousal controls the coupling between apical and somatic integration zones thus modifying cognitive capabilities closely associated with consciousness. Evidence relating AA to schizophrenia, sleep, and anesthesia is reviewed, and we assess theories that emphasize the relevance of AA to consciousness. Implications for theories of neocortical computation that emphasize context-sensitive modulation are summarized. We conclude that the findings concerning AA and its regulation by arousal offer a new perspective on states of consciousness, the function and evolution of neocortex, and psychopathology. Many issues worthy of closer examination arise

Co-design and content validity of the movement measurement in the early years (MoveMEY) tool for assessing movement behaviour of pre-school aged children

Abstract Background Movement behaviours (physical activity, sedentary behaviour, and sleep) are important for pre-school children’s health and development. Currently, no tools with appropriate content validity exist that concurrently capture these movement behaviours in young children. The aim of this study was to co-design and assess the content validity of a novel tool to concurrently measure movement behaviours in pre-school aged children (aged 3–4 years). Methods We followed four distinct steps to develop and assess the content validity of Movement Measurement in the Early Years (MoveMEY): (1) We conducted an extensive literature search, to identify pre-existing proxy measurement tools (questionnaires and diaries) to inform the design of a novel tool, which aimed to effectively capture movement behaviour guidelines of pre-school aged children. (2) We facilitated focus group discussions with parents and carers of pre-school aged children (n = 11) and (3) a qualitative survey with free text responses was completed by topic relevant researchers (n = 6), to co-design the measurement tool. (4) We assessed the content validity of the developed tool, MoveMEY, through interviews with parents of pre-school aged children (n = 12) following piloting of the tool. Results We developed an initial version of MoveMEY based on the format of an existing questionnaire and by mapping the content of questions to the guidelines. Co-design of MoveMEY resulted in changes to the format (e.g. short questionnaire to a seven-day diary) and content (e.g. inclusion of ‘general information’ questions on illness, disabilities and sleep disturbances; question on screen time before bed). Content validity assessment demonstrated that the items of MoveMEY were relevant and comprehensive for the assessment of children’s movement behaviours. MoveMEY was felt to be comprehensible, however, parental suggestions were implemented to finalise and improve MoveMEY (e.g. adding examples to questions aiming to detect moderate to vigorous physical activity). Conclusion MoveMEY is the first co-designed measurement tool that has relevance for assessing the movement behaviour guidelines of pre-school aged children. Parent/carer and topic relevant researcher involvement throughout the development process resulted in a seven-day daily reported activity diary that is comprehensive of children’s movement behaviours and comprehensible to parents and carers

A systematic review of the validity, reliability, and feasibility of measurement tools used to assess the physical activity and sedentary behaviour of pre-school aged children

Physical activity (PA) and sedentary behaviour (SB) of pre-school aged children are associated with important health and developmental outcomes. Accurate measurement of these behaviours in young children is critical for research and practice in this area. The aim of this review was to examine the validity, reliability, and feasibility of measurement tools used to assess PA and SB of pre-school aged children. Searches of electronic databases, and manual searching, were conducted to identify articles that examined the measurement properties (validity, reliability or feasibility) of measurement tools used to examine PA and/or SB of pre-school aged children (3–7 years old). Following screening, data were extracted and risk of bias assessment completed on all included articles. A total of 69 articles, describing 75 individual studies were included. Studies assessed measurement tools for PA (n = 27), SB (n = 5), and both PA and SB (n = 43). Outcome measures of PA and SB differed between studies (e.g. moderate to vigorous activity, step count, posture allocation). Most studies examined the measurement properties of one measurement tool only (n = 65). Measurement tools examined included: calorimetry, direct observation, combined heart rate and accelerometry, heart rate monitors, accelerometers, pedometers, and proxy report (parent, carer or teacher reported) measures (questionnaires or diaries). Studies most frequently assessed the validity (criterion and convergent) (n = 65), face and content validity (n = 2), test-retest reliability (n = 10) and intra-instrument reliability (n = 1) of the measurement tools. Feasibility data was abstracted from 41 studies. Multiple measurement tools used to measure PA and SB in pre-school aged children showed some degree of validity, reliability and feasibility, but often for different purposes. Accelerometers, including the Actigraph (in particular GT3X versions), Actical, ActivPAL and Fitbit (Flex and Zip), and proxy reported measurement tools used in combination may be useful for a range of outcome measures, to measure intensity alongside contextual information

Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas

AbstractObjectivesJaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours.MethodsThirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P‐value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection.ResultsPreoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five‐year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage.ConclusionsPreoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect

The health of women and girls determines the health and well-being of our modern world: A White Paper From the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally

Interventions to prevent obesity in children aged 5 to 11 years old

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. The overall aim of the review is to determine the effectiveness of interventions to prevent obesity in 5 to 11-year-old children. The four objectives are:. to evaluate the effects of interventions that aim to modify dietary intake on changes in zBMI score, BMI and serious adverse events among children; to evaluate the effects of interventions that aim to modify physical activity, sedentary behaviour, sleep, play and/or structured exercise on changes in zBMI score, BMI and serious adverse events among children; to evaluate the combined effects of interventions that aim to modify both dietary intake and physical activity/movement behaviours on changes in zBMI score, BMI and serious adverse events among children; to compare the effects of interventions that aim to modify dietary interventions with those that aim to modify physical activity/movement behaviours on changes in zBMI score, BMI and serious adverse events among children. The secondary objectives are designed to explore if, how, and why the effectiveness of interventions on zBMI/BMI varies depending on the following PROGRESS factors. Place of residence Race/ethnicity/culture/language Occupation Gender/sex Religion Education Socioeconomic status Social capital. The PROGRESS acronym is intended to ensure that there is explicit consideration of health inequity, the unfair difference in disease burden, when conducting research and adapting research evidence to inform the design of new interventions (O'Neill 2014). The PROGRESS acronym describes factors that contribute to health inequity. Recent work on race and religion in the UK suggests that consideration of these factors is critical to the design of new interventions (Rai 2019). We will also collect, from RCTs, information about the costs of interventions so that policymakers can use the review as a source of information from which they may prepare cost-effectiveness analyses

Interventions to prevent obesity in children aged 12 to 18 years old

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. The overall aim of the review is to determine the effectiveness of interventions to prevent obesity in 12 to 18-year-old children and adolescents. The four objectives are:. to evaluate the effects of interventions that aim to modify dietary intake on changes in zBMI score, BMI and serious adverse events among children and adolescents; to evaluate the effects of interventions that aim to modify physical activity, sedentary behaviour, sleep, play and/or structured exercise on changes in zBMI score, BMI and serious adverse events among children and adolescents; to evaluate the combined effects of interventions that aim to modify both dietary intake and physical activity/movement behaviours on changes in zBMI score, BMI and serious adverse events among children and adolescents; to compare the effects of interventions that aim to modify dietary interventions with those that aim to modify physical activity/movement behaviours on changes in zBMI score, BMI and serious adverse events among children. The secondary objectives are designed to explore if, how, and why the effectiveness of interventions on zBMI/BMI varies depending on the following PROGRESS factors. Place of residence Race/ethnicity/culture/language Occupation Gender/sex Religion Education Socioeconomic status Social capital. The PROGRESS acronym is intended to ensure that there is explicit consideration of health inequity, the unfair difference in disease burden, when conducting research and adapting research evidence to inform the design of new interventions (O'Neill 2014). The PROGRESS acronym describes factors that contribute to health inequity. Recent work on race and religion in the UK suggested that consideration of these factors is critical to the design of new interventions (Rai 2019). We will also collect, from RCTs, information about the costs of interventions so that policymakers can use the review as a source of information from which they may prepare cost-effectiveness analyses

Identifying and prioritising unanswered research questions for people with hyperacusis: James Lind Alliance Hyperacusis Priority Setting Partnership

Objective To determine research priorities in hyperacusis that key stakeholders agree are the most important. Design/setting A priority setting partnership using two international surveys, and a UK prioritisation workshop, adhering to the six-staged methodology outlined by the James Lind Alliance. Participants People with lived experience of hyperacusis, parents/carers, family and friends, educational professionals and healthcare professionals who support and/or treat adults and children who experience hyperacusis, including but not limited to surgeons, audiologists, psychologists and hearing therapists. Methods The priority setting partnership was conducted from August 2017 to July 2018. An international identification survey asked respondents to submit any questions/uncertainties about hyperacusis. Uncertainties were categorised, refined and rephrased into representative indicative questions using thematic analysis techniques. These questions were verified as ‘unanswered’ through searches of current evidence. A second international survey asked respondents to vote for their top 10 priority questions. A shortlist of questions that represented votes from all stakeholder groups was prioritised into a top 10 at the final prioritisation workshop (UK). Results In the identification survey, 312 respondents submitted 2730 uncertainties. Of those uncertainties, 593 were removed as out of scope, and the remaining were refined into 85 indicative questions. None of the indicative questions had already been answered in research. The second survey collected votes from 327 respondents, which resulted in a shortlist of 28 representative questions for the final workshop. Consensus was reached on the top 10 priorities for future research, including identifying causes and underlying mechanisms, effective management and training for healthcare professionals. Conclusions These priorities were identified and shaped by people with lived experience, parents/carers and healthcare professionals, and as such are an essential resource for directing future research in hyperacusis. Researchers and funders should focus on addressing these priorities.Additional co-authors: Tracey Pollard, Helen Henshaw, Toto A Gronlund, Derek J Hoar

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin