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The article focuses on the elevated risk of early maternal death among women whose children have been removed from their care, drawing on observational data from Pause, a UK-based charity. It highlights the critical health and social vulnerabilities faced by these mothers, including mental health issues, domestic abuse, and substance misuse, which are inadequately addressed by current child-focused services.

Aims: This study aimed to describe the natural history and predictors of all‐cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). Methods and results: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS‐LAH)]. One hundred forty‐nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan‐like syndrome, and 3 (2%) NS‐LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36–80) mmHg, P = 0.004]. Over a median follow‐up of 197.5 [inter‐quartile range (IQR) 93.58–370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6–175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69–98.51], 90.42% (95% CI 84.04–94.33), and 84.12% (95% CI 75.42–89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non‐sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all‐cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. Conclusions: These findings highlight a distinct category of patients with Noonan‐like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy‐related HCM. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to identify original insights into the educational social mobility conundrum in the UK via examination of the current body of empirical and existing literature associated with disadvantaged secondary school students. The lens of the 'psychosocial and academic trust alienation theory' (PATA) has been applied to explore themes of educational social mobility disadvantage, disengagement and alienation and trauma and trust. This systematic literature review followed PRISMA guidelines, with the SPIDER model adopted to demonstrate the search strategy employed which identified N = 58 publications for inclusion. The contribution of this research to the field of children, young people and society is three‐fold: Firstly, findings provide evidence of the additional educational psychological theory. Secondly, secondary education is identified as a pivotal milestone, where efforts to drive change for educational progress contributing to social mobility progress for disadvantaged students could be focused. Thirdly, the synthesis of current research and literature, identified that there is currently no existing literature related to the PATA theory positioned within the disadvantaged secondary school student context aligned to educational social mobility. This analysis shows that the issues experienced in the education system by disadvantaged students in secondary education correlate with the layered elements of the PATA theory, providing justification for further empirical research. Additionally, the insights reported here could be of interest to the children and young people sector, educational psychology community, educational policy‐makers and international groups who share similar social policy, social mobility demographics and educational systems. [ABSTRACT FROM AUTHOR]

Introduction: To understand when knowledge objects in a computable biomedical knowledge library are likely to be subject to regulation as a medical device in the United Kingdom. Methods: A briefing paper was circulated to a multi‐disciplinary group of 25 including regulators, lawyers and others with insights into device regulation. A 1‐day workshop was convened to discuss questions relating to our aim. A discussion paper was drafted by lead authors and circulated to other authors for their comments and contributions. Results: This article reports on those deliberations and describes how UK device regulators are likely to treat the different kinds of knowledge objects that may be stored in computable biomedical knowledge libraries. While our focus is the likely approach of UK regulators, our analogies and analysis will also be relevant to the approaches taken by regulators elsewhere. We include a table examining the implications for each of the four knowledge levels described by Boxwala in 2011 and propose an additional level. Conclusions: If a knowledge object is described as directly executable for a medical purpose to provide decision support, it will generally be in scope of UK regulation as "software as a medical device." However, if the knowledge object consists of an algorithm, a ruleset, pseudocode or some other representation that is not directly executable and whose developers make no claim that it can be used for a medical purpose, it is not likely to be subject to regulation. We expect similar reasoning to be applied by regulators in other countries. [ABSTRACT FROM AUTHOR]

This is an example of the training data used to learn how to predict lowest cloud-base height using a neural network. Using machine learning to find cloud-base height: a didactic challenge The actual lowest cloud base (for cloud fraction greater than 2 oktas) is shown by a red line in (c) and the most likely location of lowest cloud base is shown by the green line in (d). gl Setting the challenge A Data Science Community of Practice meets around once a month at the Met Office. The first network was used to determine whether there was any cloud to be found and then the second network tried to find the cloud base when it thought there was cloud to be found. [Extracted from the article]

Arterial medial calcification (AMC) is the deposition of calcium phosphate in the arteries. AMC is widely thought to share similarities with physiological bone formation; however, emerging evidence suggests several key differences between these processes. N‐acetylcysteine (NAC) displays antioxidant properties and can generate hydrogen sulphide (H2S) and glutathione (GSH) from its deacetylation to l‐cysteine. This study found that NAC exerts divergent effects in vitro, increasing osteoblast differentiation and bone formation by up to 5.5‐fold but reducing vascular smooth muscle cell (VSMC) calcification and cell death by up to 80%. In vivo, NAC reduced AMC in a site‐specific manner by 25% but had no effect on the bone. The actions of l‐cysteine and H2S mimicked those of NAC; however, the effects of H2S were much less efficacious than NAC and l‐cysteine. Pharmacological inhibition of H2S‐generating enzymes did not alter the actions of NAC or l‐cysteine; endogenous production of H2S was also unaffected. In contrast, NAC and l‐cysteine increased GSH levels in calcifying VSMCs and osteoblasts by up to 3‐fold. This suggests that the beneficial actions of NAC are likely to be mediated via the breakdown of l‐cysteine and the subsequent GSH generation. Together, these data show that while the molecular mechanisms driving the actions of NAC appear similar, the downstream effects on cell function differ significantly between osteoblasts and calcifying VSMCs. The ability of NAC to exert these differential actions further supports the notion that there are differences between the development of pathological AMC and physiological bone formation. NAC could represent a therapeutic option for treating AMC without exerting negative effects on bone. [ABSTRACT FROM AUTHOR]

Disasters including public health crises like the COVID‐19 pandemic are known to increase instances of family violence against women, children, and other diverse populations. This paper discusses and provides evidence of disaster‐related vulnerability of and violence towards specific groups of people. We argue that the COVID‐19 pandemic presents the 'perfect storm' for family violence, where a set of rare circumstances combine, resulting in a significant aggravation of the resulting event. Given the mental health implications of family violence, mental health professionals need to be aware of this issue during the pandemic and ready to assist with the development of strategies to overcome the situation where possible. To provide protection and prevent violence, there is a need to include at‐risk groups in disaster response and community planning. Such a plan could involve gender and disaster working groups at the local community, state, and national levels. [ABSTRACT FROM AUTHOR]

Background: Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations. Methods: A retrospective cohort study using the 'The Health Improvement Network,' (UK primary care medical records) between 1st January 1995–31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow‐up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health. Results: During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85–2.80), chronic headaches (aIRR 3.15; 95% CI 1.07–9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25–1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44–2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14–1.93), vulvodynia (aIRR 0.42; 95% CI 0.14–1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28–3.61). Conclusion: This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse. Significance: Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences. [ABSTRACT FROM AUTHOR]

Acute malnutrition in infants under 6 months (u6m) is increasingly recognised as a global public health problem. The World Health Organisation (WHO) guidelines for inpatient nutritional rehabilitation of infants u6m is re‐lactation: the re‐establishment of exclusive breastfeeding. Evidence suggests these guidelines are rarely followed in many low‐income settings. Two studies of infant nutritional rehabilitation undertaken in three public hospitals in coastal Kenya employed breastfeeding peer supporters (BFPSs) to facilitate WHO guideline implementation. To explore the acceptability of the strategy to health workers (HWs) and the BFPSs, in‐depth interviews were conducted with 20 HWs and five BFPSs in the three study hospitals. The HWs reported that the presence of the BFPSs changed the way infant nutritional rehabilitation was managed, increasing efforts at relactation and decreasing reliance on supplemental milk. BFPSs were said to help address staff shortages and had dedicated time to support and assist the mothers. Key to the success of the BFPSs was the social relationships they were able to establish with the mothers due to the similarity in their experiences and backgrounds. Despite the success of the BFPSs, human resource management and infrastructure challenges remained. BFPSs can successfully be employed to facilitate the implementation of the WHO guidelines for the nutritional rehabilitation of acutely malnourished infants u6m in hospitals in Kenya, establishing supportive social relationships and trust with the mothers of the acutely malnourished infants and helping to address the issue of human resource shortages. [ABSTRACT FROM AUTHOR]

Key Practitioner Messages: Closed, often tight‐knit army communities can potentially provide protective factors for children; however, this environment can make it difficult to seek help or to speak out when there are concerns about children's safety or wellbeing.The needs and experiences of non‐serving parents (often female partners) can be overlooked unless, or until, child protection concerns are serious.Army‐connected children benefit from accessing army and civilian health, education and welfare services; however, transitions and communication between these services need to be improved. [ABSTRACT FROM AUTHOR]

There has been increasing debate in recent years about the conceptualization of moral distress. Broadly speaking, two groups of scholars have emerged: those who agree with Jameton's 'narrow definition' that focuses on constraint and those who argue that Jameton's definition is insufficient and needs to be broadened. Using feminist empirical bioethics, we interviewed critical care nurses in the United Kingdom about their experiences and conceptualizations of moral distress. We provide our broader definition of moral distress and examples of data that both challenge and support our conceptualization. We pre‐empt and overcome three key challenges that could be levelled at our account and argue that there are good reasons to adopt our broader definition of moral distress when exploring prevalence of, and management strategies for, moral distress. [ABSTRACT FROM AUTHOR]

Rationale: This study analyzes variability in the diets of wild bearded capuchin monkeys, Sapajus libidinosus, by analyzing stable carbon (δ13C) and nitrogen (δ15N) isotope ratios and elemental concentrations (%C and %N) of fecal samples and food items. Developing isotopic and elemental correlates for diets of habituated subjects is a necessary step towards applying similar methods to interpret diets of unhabituated or cryptic subjects. Methods: Fecal samples from wild capuchins and their foods were collected at Fazenda Boa Vista, Brazil. Fecal samples from laboratory-housed Sapajus spp. and their foods were analyzed to establish diet-feces offsets for δ13C, δ15N, %C, and %N. Samples were dried, powdered, and measured for isotopic and elemental values. A Bayesian mixing model commutes isotopic and elemental data from wild capuchins into likely proportions of different food categories. Results: The captive study shows small diet-feces spaces for Sapajus spp. of −0.8 ± 0.7‰ for δ13C, −0.2 ± 0.4‰ for δ15N, −6.1 ± 1.7% for %C, and −1.0 ± 0.6% for %N. The wild study shows omnivorous diets based on C3, C4, and CAM plants, and fauna. Subject diets are highly varied within and between days. Fecal data show age-related differences in diet and crop-raiding. There is no consistent isotopic or elemental difference between mothers and infants. Conclusions: Fecal stable isotope and elemental evidence employed in a Bayesian mixing model reflects the highly varied diets of capuchin monkeys in an isotopically heterogeneous environment. The isotopic and elemental variability reported here will aid similar diet reconstructions among unhabituated subjects in the future, but precludes tracking weaning isotopically among capuchins in this environment. [ABSTRACT FROM AUTHOR]

Re‐establishment and maintenance of exclusive breastfeeding (EBF) is recommended by the World Health Organization for the nutritional rehabilitation of malnourished infants under 6 months; however, there is no explicit guidance on how this should be achieved. The IBAMI study—a pilot study conducted in Kilifi, Kenya—implemented these recommendations using an intervention for hospitalized infants and their mothers that included ward‐based breastfeeding peer supporters. This paper explores how the challenges of maintaining EBF are recontextualized after infant hospitalization for malnutrition. Four weeks after discharge, semistructured interviews on experiences of trying to maintain EBF in a postdischarge home setting were conducted with a total of 20 mothers. Although most stated the aspiration of maintaining EBF for 6 months, a range of challenges were reported and not all had successfully maintained EBF post discharge. Reported challenges include the stress of household chores, food insecurity, technical difficulties and social stigma of expressing breast milk, pressure from neighbours and family members to introduce mixed feeding, and needing more community‐based awareness and support. Most of these challenges were specific to the home setting and were not easily surmountable, despite the breastfeeding practices mothers had learned in the ward. Indeed, in some cases, challenges were exacerbated by the overmedicalized nature of the breastfeeding practices taught in the ward. In order to aid the transition from ward to home, there may be a need to further translate ward‐based education and promotional messaging for EBF into a community setting, targeting other caregivers as well. [ABSTRACT FROM AUTHOR]

This article is the fourth in a series introducing the reader to methods and theories relevant to advancing socio‐legal research. They are written for the curious rather than the expert reader and provide illustrations of how the theories, methods, and frameworks have been employed and might be used in your work. This article explores the use of case biography methods for socio‐legal studies. Drawing on 'paths to justice' studies, network analysis, and legal archaeology, we develop a case study of AC v.Berkshire West Primary Care Trust. We show how the judicial determination of the case suppressed a transgender rights narrative construction of the dispute in favour of one about health care law. Our case biography analysis explores how competing narratives can be traced not only through legal argument and literature, but also through the personnel involved, in ways that are obscured by formal records. Paying attention to biographical features leads to a richer understanding of cases, including the importance of pre‐ and post‐judicial decision‐making aspects. [ABSTRACT FROM AUTHOR]

An experimental study with captive individuals and study of video recordings of wild monkeys explored whether and how tufted capuchin monkeys use onehand to hold one or more objects with multiple grips (compound grips). A task designed to elicit compound grip was presented to five captive tufted capuchin monkeys (Sapajus spp). The monkeys held one to four balls in onehand and dropped the balls individually into a vertical tube. Multiple simple grips and independent digit movements enabled separate control of multiple objects in one hand. Monkeys always supported the wrist on the horizontal edge of the tube before releasing the ball. Increasing the number of balls decreased the likelihood that the monkeys managed the task. Wild bearded capuchins (Sapajus libidinosus) used compound grips spontaneously to store multiple food items. Compound grips have been described in macaques, gorillas, chimpanzees, and humans, and now in a New World primate. We predict that any primate species that exhibits precision grips and independent digit movement can perform compound grips. Our findings suggest many aspects of compound grip that await investigation. Research Highlights: Captive tufted capuchins used multiple grips to control separately more than one object in the same hand (compound grips).Wild tufted capuchins held more than one nut in one hand and used compound grips to move them within the hand.Capuchin monkeys, and likely other species of nonhuman primates, use compound grips previously identified in a few species of Old World monkeys and apes. [ABSTRACT FROM AUTHOR]

There is a growing body of experimental and clinical evidence supporting mineralocorticoid receptor (MR) activation as a powerful mediator of renal damage in laboratory animals and humans. Multiple pathophysiological mechanisms are proposed, with the strongest evidence supporting aldosterone‐induced vasculopathy, exacerbation of oxidative stress and inflammation, and increased growth factor signalling promoting fibroblast proliferation and deranged extracellular matrix homeostasis. Further involvement of the MR is supported by extensive animal model experiments where MR antagonists (such as spironolactone and eplerenone) abrogate renal injury, including ischaemia‐induced damage. Additionally, clinical trials have shown MR antagonists to be beneficial in human chronic kidney disease (CKD) in terms of reducing proteinuria and cardiovascular events, though current studies have not evaluated primary end points which allow conclusions to made about whether MR antagonists reduce mortality or slow CKD progression. Although differences between human and feline CKD exist, feline CKD shares many characteristics with human disease including tubulointerstitial fibrosis. This review evaluates the evidence for the role of the MR in renal injury and summarizes the literature concerning aldosterone in feline CKD. MR antagonists may represent a promising therapeutic strategy in feline CKD. [ABSTRACT FROM AUTHOR]

Family carers affected by violent, abusive or harmful behaviour by the older person for whom they care face social and epistemic challenges in developing and sharing knowledge about their experiences. These difficulties have contributed to a situation in which there is a paucity of evidence and public discourse about how we understand violence and harm instigated by people who have care needs or are 'vulnerable'. This paper reports the findings of a qualitative study that involved 12 in‐depth interviews with female carers affected by violence, abuse or harm. The study was informed theoretically by Miranda Fricker's concept of epistemic injustice which was used as a framework for analysis. There were two principal findings: (1) Carers were sensitive to anticipatory stigma and loss of moral autonomy. As a result, they self‐censured what they shared and, at times, were met with subtle but powerful processes of silencing. (2) Carers had limited linguistic and conceptual resources to explain the emotional and social aspects of the harm they experienced, exacerbated by implicit social norms about the 'private' and gendered nature of familial care. To conclude, we discuss the implications of these findings for sociological research and health and social care practice. [ABSTRACT FROM AUTHOR]

Disparities in children's early language skills associated with socioeconomic factors have led to many studies examining children's early language environments, but few as yet in the first year of life. This longitudinal study assessed the home language environments of 50 Australian infants, who varied in maternal education (university education, or not). Full‐day audio recordings were collected and analyzed using the LENA system when infants were aged 6–9 months and 12–15 months. Using the device‐specific analysis software, we assessed 12‐h projected counts of (1) adult speech input, (2) conversational interactions, and (3) child vocalizations. At both ages, higher maternal education was associated with higher counts of adult words and conversational turns, but not child vocalizations. The study adds to the literature by demonstrating disparities in the infants' language experience within the first year of life, related to mothers' education, with implications for early intervention and parenting supports. [ABSTRACT FROM AUTHOR]

Babies born with the inherited condition albinism, resulting in reduced melanin pigment in their hair, skin and eyes, are vulnerable in multiple ways in Africa: as children, as visually impaired, as socially ostracised, isolated and excluded, and as potential victims of witchcraft‐related violence targeted for their body parts for use in 'lucky' charms thought to bring good fortune. This conceptual review summarises the scarce research on this topic within an integrated framework of otherness (highlighting the ways in which these children differ from others in their group and how this is perceived by themselves and others), watchfulness (the consequences and impact of this very visible difference on families and communities) and agency (what such children themselves and other people can do to respond to these abuses of human rights). The paucity of information on the lives of children with albinism in Africa limits the development of appropriate interventions to support, empower and, most importantly, protect them at this time of danger in the region. This review proposes a conceptual model to act as a platform for research on which to build and enhance our understanding of the lives of children with albinism in sub‐Saharan Africa. 'This conceptual review summarises the scarce research on this topic within an integrated framework of otherness..., watchfulness... and agency' Key Practitioner Messages: Mutilation and killing of people with albinism, particularly children, have increased over recent years.Very little is known about the physical and psychosocial issues facing children with albinism in the context of threats of assault and attack.Children with albinism are seen as 'other', with the violent context making them and their families watchful and vigilant. This threatens their agency and safety. [ABSTRACT FROM AUTHOR]

Extractive foraging is a skill young capuchin monkeys learn over time. A key unknown is whether unskilled individuals occupy spatial positions that increase their opportunities to learn. We observed the spatial positions of individuals in a group of capuchin monkeys in Northeastern Brazil. To improve our understanding of the relationship between learning by young capuchin monkeys and inter‐individual distance, we investigated the associations between the proximity of individuals and their age, activity, and proficiency at extractive foraging. To do this, we used one form of extractive foraging, opening palm nuts, as an index of proficiency at all types of extractive foraging. Our results indicate that, in the subset of the data where dyads consisted of one proficient individual and a partner with any level of proficiency, the distance between individuals was predicted by their foraging activity (i.e., extractive foraging, other foraging, or not foraging). In those dyads, the proficiency of the partner did not significantly improve prediction of inter‐individual distances, indicating that spatial proximity of proficient individuals to others does not function primarily to increase opportunities for unskilled individuals to observe extractive foraging. Dyads in which both individuals were engaged in similar foraging activities (e.g., both “extractive foraging”) exhibited the shortest inter‐individual distances. Proximity between individuals engaged in similar foraging activities may result from the spatial distribution of resources or from social learning mechanisms, such as local or stimulus enhancement. [ABSTRACT FROM AUTHOR]

Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PPi), dose dependently inhibited VSMC calcification by ≤85%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PPi reduced apoptosis to levels seen in non-calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100-fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAPactivity (≤50%) but stimulatedVSMCTNAP activity (≤88%). The effects of extracellular nucleotides onVSMCcalcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y2 receptor. Conversely, the actions of ATP/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y2 receptor. Ecto-nucleotide pyrophosphatase/ phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PPi. In both VSMCsand osteoblasts, deletion ofNPP1blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences have a strong negative impact on health and are a significant public health concern. Adverse childhood experiences, including various forms of child maltreatment, together with their mental health sequelae (eg, posttraumatic stress disorder, depression, dissociation) also contribute to adverse pregnancy outcomes (eg, preterm birth, low birth weight), poor postpartum mental health, and impaired or delayed bonding. Intergenerational patterns of maltreatment and mental health disorders have been reported that could be addressed in the childbearing year. Trauma-informed care is increasingly used in health care organizations and has the potential to assist in improving maternal and infant health. This article presents an overview of traumatic stress sequelae of childhood maltreatment and adversity, the impact of traumatic stress on childbearing, and technical assistance that is available from the National Center for Trauma-Informed Care (NCTIC) before articulating some steps to conceptualizing and implementing trauma-informed care into midwifery and other maternity care practices. [ABSTRACT FROM AUTHOR]

Context: Acute illness is a universal experience in early childhood. Parents find it difficult to determine whether or not their child requires medical care and seek information to inform their decision making. Little is known about parents' information seeking behaviour and what helps or hinders their decision making. Objective: This study aimed to explore parents' use of information resources during decision making in acute childhood illness at home. Design/Method: This exploratory qualitative study used focus groups and interviews to collect data from parents of children under 5 years of age. Setting and participants: Twenty‐seven parents were recruited in the East Midlands, UK, in South Asian and Gypsy/Travelling communities, a Children's Centre and a private sector day nursery. Findings: Parents' pre‐consultation information seeking was dominated by the internet, albeit with limited success. Parents liked easy to access, professionally validated and simple messages with access to more detailed information. Some parents always sought information through personal contact, whilst others did so when independent information seeking failed. When consulting a healthcare professional, parents liked to be given information to refer to later, although the information received varied. Importantly, neither hard copy nor the internet was accessible for parents with low levels of literacy. Discussion and conclusions: Although there is a wealth of information parents can access independently, our findings indicate a need for easy access to clearly signposted, professionally validated resources and available in a range of formats provided through different delivery systems. One size does not fit all. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including issues related to maternal protectiveness, report on the methodology of Domestic Abuse Recovering Together (DART) and safeguarding mothers and children from domestic violence.

Looked after children are significantly more likely than other children to go missing. They face significant risk of harm through, for example, exposure to alcohol, drugs and sexual victimisation. While research identifies some factors which may reduce the likelihood of looked after children going missing, it is recognised that a greater understanding of effective practice is needed. The aim of the study was to investigate young people's experiences of going missing from care and to identify the issues that contributed to them running away; trigger factors that prompted episodes of going missing; support received during or following instances where they went missing; and factors that might prevent future absconding. Research on children's experiences is often reported from the adult's perspective rather than allowing children to have a voice. We therefore recruited two young people to collaborate with the researchers as peer researchers. A qualitative study was undertaken using the Critical Incident Technique. Twenty-eight young people with a history of running away were recruited from different locations in Scotland. They took part in six focus groups, which were held during May 2012. Data were analysed using a framework approach. Four themes were identified regarding reasons for running away: authority and power; friction; isolation; and environmental issues. Commonly cited consequences were being 'grounded' and having shoes removed (to prevent further running away). Young people were critical of a lack of support on return and a lack of boundaries. They stressed the importance of being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares. Copyright © 2013 John Wiley & Sons, Ltd. Key Practitioner Messages Looked after children are significantly more likely than other children to go missing., When missing, young people are exposed to significant risk of harm., Reasons for running away are: authority and power; friction; isolation; and environmental issues., Approaches to responding to young people who go missing should be supportive and facilitative rather than punitive., Being heard, being treated with respect, being able to exercise autonomy and feeling that someone cares are crucial preventative factors. [ABSTRACT FROM AUTHOR]

Children's sleep is critical for optimal health and development; yet sleep duration has decreased in recent decades, and many children do not have adequate sleep. Certain sleep behaviours ('sleep hygiene') are commonly recommended, and there is some evidence that they are associated with longer nighttime sleep. Parents of 84 British 3-year-old children were interviewed about their children's sleep and completed five-night/four-day sleep diaries documenting their children's sleep, from which daily sleep duration was estimated. Diaries were validated by actigraphy in a subgroup of children. Sleep hygiene behaviours (regular bedtime, reading at bedtime, falling asleep in bed) were associated with each other, and were more common in the high socioeconomic status compared to the low socioeconomic status group. Parents' reasons for not practicing sleep hygiene included difficulty, inability or inconvenience. Sleep hygiene behaviours were associated with significantly longer child sleep at night but not over 24 h. Longer daytime napping compensated for shorter nighttime sleep in children whose parents did not implement sleep hygiene behaviours. Parents may need to be advised that certain behaviours are associated with longer nighttime sleep and given practical advice on how to implement these behaviours. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Judges articulate their role in controversial cases of medical ethics in terms of deference to Parliament, lest their personal morality be improperly brought to bear. This hides a wide range of law-making activities, as parliamentary sovereignty is diffused by 'intermediate law-makers', and judicial activity is more subtle than the deference account implies. The nature of litigation raises questions about the contributions of other legal personnel and also the nature of the parties' interests in test-cases. While judges demonstrate an awareness of some of these issues and anxiety about the constitutional legitimacy of their work, a more nuanced account is needed of their proper role. This may be built on Austin's theory of tacit legislation. It may draw from human rights law. However, considerable work is required before the complexities of hidden law-making can be properly incorporated into the province of medical jurisprudence. [ABSTRACT FROM AUTHOR]

This article examines current understandings regarding the causes of child maltreatment and its prediction and prevention. The answers to why some people hurt children, when others in similar circumstances do not, remain obstinately elusive. We look to philosophy to help understand the complexity of causal pathways of maltreatment. We draw on the seminal work of Mackie () on probabilistic causation and his notion of the 'INUS condition' (INUS is the acronym for insufficient but non-redundant part of a condition that is itself unnecessary but sufficient for the result). This theory holds particular relevance for exploring complex social phenomena. Taking child abuse as an issue, we show how the concept of the INUS condition offers a new way of thinking about causal factors when they are neither necessary nor sufficient. It can be applied to clarify the complex nexus of potential risk factors that may - or may not - 'cause' adult perpetration of abuse. It also provides a framework for integrating the research on resilience factors with that on risk. Finally, we discuss the lessons for research, policy and practice that arise from this way of conceptualising the underlying causality of child maltreatment. Copyright © 2013 John Wiley & Sons, Ltd. Key Practitioner Messages: There have been major efforts to create models of risk and prediction in child protection but it remains an imprecise science., Risk factors appear to be neither necessary nor sufficient conditions for maltreatment to occur., In this article, we adopt a philosophical position to help make sense of the complex causation of maltreatment., We show the implications of these new perspectives for health and social care policy and practice. [ABSTRACT FROM AUTHOR]

Domestic abuse is a worldwide public health issue with long-term health and social consequences. Nurses play a key role in recognizing and responding to domestic abuse. Yet there is considerable evidence that their responses are often inappropriate and unhelpful, such as trivializing or ignoring the abuse. Empirical studies have identified several reasons why nurses' responses are sometimes wanting. These include organizational constraints, e.g. lack of time and privacy; and interpersonal factors such as fear of offending women and lack of confidence. We propose, however, that these factors present only a partial explanation. Drawing on the work of Julia Kristeva, we suggest that alternative understandings may be derived through applying the concept of abjection. Abjection is a psychological defence against any threat (the abject) to the clean and proper self that results in rejection of the abject. Using examples from our own domestic abuse research, we contend that exposure of nurses to the horror of domestic abuse evokes a state of abjection. Domestic abuse (the abject) transgresses established social boundaries of clean and proper. Thus when exposed to patients' and clients' experiences of it, some nurses subconsciously reject domestic abuse as a possibility (abjection). They do this to protect themselves from the horror of the act, but in so doing, render themselves unable to formulate appropriate responses. Rather than understanding the practice of some nurses as wilfully neglectful or ignorant, we argue that through a state of abjection, they are powerless to act. This does not refute existing evidence about nurses' responses to domestic abuse. Rather, as a relatively unknown concept in nursing, abjection provides an additional explanatory layer that accounts for why some nurses respond the way they do. Crucially, it elucidates the need for nurses to be supported emotionally when faced with the transgressive practice of abuse. [ABSTRACT FROM AUTHOR]

Following severe burns and trauma injuries, the changes of neutrophil migratory phenotype are a double-edged sword. Activated neutrophils migrate into injured tissues and help contain microbial infections, but they can also enter normal tissues and damage vital organs. Depleting the neutrophils from circulation protects vital organs against neutrophil-induced damage but leaves the body exposed to infectious complications. Here we show that restoring normal neutrophil migratory phenotype in rats with burnn injuries correlates with improved survival in a classical double-injury model of sequential burn and septic insults. We uncovered that the directionality of neutrophils from burned rats can be restored both in vitro by 1 nM resolvin D2 (RvD2) and in vivo by RvD2 for 7 d, 25 ng/kg body mass (8-10 ng/rat). Restoring neutrophil directionality dramatically increases survival after a second septic insult at d 9 postburn. Survival of RvD2-treated animals increases from 0 to 100% after lipopolysaccharide injection and is extended by 1 wk after cecal ligation. Survival does not significantly increase when the restoration of neutrophil directionality is incomplete, following shorter regimens of RvD2. We conclude that restoring neutrophil directionality using RvD2 could have prophylactic value and delay lethal complications after burn injuries. [ABSTRACT FROM AUTHOR]

Flooding due to coastal storm surges presents a significant threat to life and property. The UK has long had a storm surge forecasting system based on a single 'deterministic' simulation. This was augmented with an operational storm surge ensemble in December 2009. By producing several simulations sampling the forecast uncertainty, the ensemble estimates the probability of reaching critical water levels and thus supports a more risk-based approach to civil protection. The original storm surge ensemble provided forecasts out to T + 54 h, limited by the forecast range of the driving MOGREPS-R atmospheric ensemble. Longer-range forecasts could provide advance notice of the potential for a significant event, allowing suitable preparatory actions to be taken. This study investigates the possibility of extending the storm surge ensemble to between 5 and 7 days using atmospheric data from the lower-resolution Met Office 15-day ensemble (MOGREPS-15). Both case studies and statistical verification indicate the potential for useful forecasts out to the full 7.25 days tested. The best performance is obtained by extending the existing surge ensemble products with output from separate runs of the storm surge model, which have been driven by MOGREPS-15 meteorology from T + 0 h. An attempt to create a single surge history for each member by switching from MOGREPS-R to MOGREPS-15 input at T + 54 h led to spurious oscillations in some cases, and poorer performance on several statistical measures. These issues might be improved by smoothing the discontinuity in atmospheric forcing. Following this successful trial, the separate-runs extension to the surge ensemble was implemented operationally in summer 2011. The study also demonstrates the benefit of online bias correction and 'dressing' the forecast members to account for errors which the system does not otherwise sample. The operational implementation of these features is left for future work. Copyright © 2012 British Crown copyright, the Met Office Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Distributional learning is a proposal for how infants might learn early speech sound categories from acoustic input before they know many words. When categories in the input differ greatly in relative frequency and overlap in acoustic space, research in bilingual development suggests that this affects the course of development. In the present study we describe the nature and extent of vowel variation in nearly 900 vowel tokens in maternal speech in Gurindji Kriol, a mixed language of northern Australia, which, like bilingual input, has differences in the relative frequency of adjacent, overlapping vowel categories. In Analysis 1, we provide the first systematic account of vowel variation and phone frequency in maternal speech in Gurindji Kriol. In Analysis 2, cluster analysis was applied to the vowel formant and duration data, to see what categories might emerge from acoustic data alone. The results suggest that, were infants to base their initial vowel categories solely on the clusters emerging in acoustic space, they might likely set up relatively few vowel categories. We discuss implications for how infants may learn Gurindji Kriol and for distributional learning. [ABSTRACT FROM AUTHOR]

The author comments on "Phenomenology as research method or substantive metaphysics? An overview of phenomenology's uses in nursing," by V. Earle. She refers to "Ideas" by Husserl and raises concerns inspired by him. She opines that the issue of principal explanations for why nurse researchers appear to struggle with phenomenology: the reasons why they get it wrong, is overlooked. She also argues on Earle's part citing writings by Heidegger, Gadamer and Merleau-Ponty.

Objectives: This study tested hypotheses that: (1) levels of adiposity, as assessed by triceps and subscapular skinfold thicknesses (SFTs), and blood pressure would be higher in British Pakistani children than in white British children; and (2) British Pakistani children of mothers born in the UK would have smaller SFTs and lower blood pressure than children of mothers born in Pakistan. Methods: Participants aged 7 to 11 years were recruited from five primary schools in a deprived urban area. BMI, waist circumference, triceps and subscapular SFT, and blood pressure were measured. Results: Participants comprised 209 white British and 132 British Pakistani children, including 79 children born in the UK to migrant mothers and 49 children born to British-born mothers. In comparisons by ethnic group, triceps SFT was significantly higher in British Pakistani children only after controlling for BMI. Subscapular SFT was higher in British Pakistani children, a finding strengthened after controlling for BMI. Systolic blood pressure was significantly higher in British Pakistani children, but not after controlling for socioeconomic status (SES). There were no significant differences between British Pakistani children born to migrant or British-born mothers, except that systolic blood pressure was lower in children of British-born mothers after controlling for SES, a finding that was not significant after controlling for BMI. Conclusions: This study confirms previous findings of larger SFTs and higher blood pressure in British children of Pakistani origin than in children of white European origin. Further work with larger sample sizes is needed to investigate differences between generations. Am. J. Hum. Biol., 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that ∼30-40% of human CD25hi FOXP3+ CD4+ Tregs express the peripheral CXC chemokine receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-γ production were significantly higher using CXCR3-depleted versus undepleted responders in the mixed lymphocyte reaction, as well as following mitogen-dependent activation of T cells. Using microfluidics, we also found that CXCR3 was functional on CXCR3pos Tregs, in as much as chemotaxis and directional persistence towards interferon-γ-inducible protein of 10 kDa (IP-10) was significantly greater for CXCR3pos than CXCR3neg Tregs. Following activation, CXCR3-expressing CD4+ Tregs were maintained in vitro in cell culture in the presence of the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and we detected higher numbers of circulating CXCR3+ FOXP3+ T cells in adult and pediatric recipients of renal transplants who were treated with mTOR-inhibitor immunosuppressive therapy. Collectively, these results demonstrate that the peripheral homing receptor CXCR3 is expressed on subset(s) of circulating human Tregs and suggest a role for CXCR3 in their recruitment into peripheral sites of inflammation. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs) are critical for extracellular matrix (ECM) integrity in cartilage but mechanisms regulating their synthesis are not defined. UDP-glucose dehydrogenase (UGDH) catalyses UDP-glucose oxidation to UDP-glucuronic acid, an essential monosaccharide in many GAGs. Our previous studies in articular surface (AS) cells from embryonic joints have established pivotal roles for mitogen-activated protein kinases (MAPK) in synthesis of the unsulfated GAG, hyaluronan (HA). We investigated the functional significance of UGDH in GAG production and chondrogenesis, and determined roles for MEK-ERK and p38 pathways in regulating UGDH expression and function. Inhibitors of MEK and p38 reduced UGDH protein in AS cells. Treatment with TGF-β (archetypal growth factor) increased UGDH expression, sulfated (s)-GAG/HA release and pericellular matrix formation in a p38-dependent manner. Retroviral overexpression of UGDH augmented HA/sGAG release and pericellular matrix elaboration, which were blocked by inhibiting MEK but not p38. UGDH overexpression increased cartilage nodule size in bone marrow culture, promoted chondrogenesis in limb bud micromass culture and selectively suppressed medium HA levels and modified GAG sulfation, as assessed by FACE analysis. Our data provide evidence that: (i) TGF-β regulates UGDH expression via p38 to modulate sGAG/HA secretion, (ii) MEK-ERK, but not p38 facilitates UGDH-induced HA and sGAG release, and (iii) increased UGDH expression promotes chondrogenesis directly and differential modifies GAG levels and sulfation. These results indicate a more diverse role for UGDH in the support of selective GAG production than previously described. Factors regulating UGDH may provide novel candidates for restoring ECM integrity in degenerative cartilage diseases, such as osteoarthritis.Arthritis Research Campaign. J. Cell. Physiol. 226: 749-761, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Current evidence indicates that chylomicron remnants (CMR) induce macrophage foam cell formation, an early event in atherosclerosis. Inflammation also plays a part in atherogenesis and the transcription factor nuclear factor-κB (NF-κB) has been implicated. In this study, the influence of CMR on the activity of NF-κB in macrophages and its modulation by the fatty acid composition of the particles were investigated using macrophages derived from the human monocyte cell line THP-1 and CMR-like particles (CRLPs). Incubation of THP-1 macrophages with CRLPs caused decreased NF-κB activation and downregulated the expression of phospho-p65–NF-κB and phospho-IκBα (pIκBα). Secretion of the inflammatory cytokines tumour necrosis factor α, interleukin-6 and monocyte chemoattractant protein-1, which are under NF-κB transcriptional control, was inhibited and mRNA expression for cyclooxygenase-2, an NF-κB target gene, was reduced. CRLPs enriched in polyunsaturated fatty acids compared with saturated or monounsaturated fatty acids had a markedly greater inhibitory effect on NF-κB binding to DNA and the expression of phospho-p65–NF-κB and pIκB. Lipid loading of macrophages with CRLPs enriched in polyunsaturated fatty acids compared with monounsaturated fatty acids or saturated fatty acids also increased the subsequent rate of cholesterol efflux, an effect which may be linked to the inhibition of NF-κB activity. These findings demonstrate that CMR suppress NF-κB activity in macrophages, and that this effect is modulated by their fatty acid composition. This downregulation of inflammatory processes in macrophages may represent a protective effect of CMR which is enhanced by dietary polyunsaturated fatty acids. [ABSTRACT FROM AUTHOR]

To reconstruct an indigenous language known solely from historical wordlists, the linguist needs to decide which source wordlists are most relevant, i.e. which sources are most likely to be attestations of the language to be reconstructed. There is little published research on methods appropriate to this task, and yet there is increasing attention to indigenous language reconstruction in support of language revival and revitalisation in education and community contexts. This paper 1 describes a replicable and relatively objective method for comparing lexical similarity within a set of historical sources. The method described draws on the use of measures of lexical similarity in linguistics and the use of measures of endemism in biogeography. The method is illustrated via an analysis of historical sources for Aboriginal languages from the greater Sydney region, New South Wales, Australia. The sample is used to describe the overall similarity and difference between wordlists from this region, and to identify which wordlists are most similar to the wordlist recorded by the surveyor R. H. Mathews (e.g. 1903) as Darkinyung language. [ABSTRACT FROM AUTHOR]

Communication between endothelial and bone cells is crucial for controlling vascular supply during bone growth, remodeling, and repair but the molecular mechanisms coordinating this intercellular crosstalk remain ill-defined. We have used primary human and rat long bone-derived osteoblast-like cells (HOB and LOB) and human umbilical vein endothelial cells (HUVEC) to interrogate the potential autocrine/paracrine role of vascular endothelial cell growth factor (VEGF) in osteoblast:endothelial cell (OB:EC) communication and examined whether prostaglandins (PG), known modulators of both OB and EC behavior, modify VEGF production. We found that the stable metabolite of PGI2, 6-keto-PGF1α and PGE2, induced a concentration-dependent increase in VEGF release by HOBs but not ECs. In ECs, VEGF promoted early ERK1/2 activation, late cyclooxygenase-2 (COX-2) protein induction, and release of 6-keto-PGF1α. In marked contrast, no significant modulation of these events was observed in HOBs exposed to VEGF, but LOBs clearly exhibited COX-dependent prostanoid release (10-fold less than EC) following VEGF treatment. A low level of osteoblast-like cell responsiveness to exogenous VEGF was supported by VEGFR2/Flk-1 immunolabelling and by blockade of VEGF-mediated prostanoid generation by a VEGFR tyrosine kinase inhibitor (TKI). HOB alkaline phosphatase (ALP) activity was increased following long-term non-contact co-culture with ECs and exposure of ECs to VEGF in this system further increased OB-like cell differentiation and markedly enhanced prostanoid release. Our studies confirm a paracrine EC-mediated effect of VEGF on OB-like cell behavior and are the first supporting a model in which prostanoids may facilitate this unidirectional VEGF-driven OB:EC communication. These findings may offer novel regimes for modulating pathological bone remodeling anomalies through the control of the closely coupled vascular supply. J. Cell. Physiol. 214: 537–544, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Title. Exploring research supervision through Peshkin’s I’s: the yellow brick road Aim. This paper is a report of a systematic approach used to explore subjectivity as a research student and demonstrates how the process enhanced the quality of the research experience. Background. High non-completion rates of research students are of global concern and means of enhancing the quality of the doctoral experience are needed. Among the literature on doctoral education, very little is authored by students. This paper is influenced by the work of Peshkin from the discipline of education. Peshkin articulated the need for researchers to systematically identify their subjectivity by searching for their subjective I’s. I share my experience of adopting this approach as a research student by using reflexive journal entries made during 2005–2007 as data. Findings. I use the analogy of the ‘Yellow Brick Road’ from The Wizard of Oz to represent my experience of being a doctoral student and draw comparisons between my subjectivity and the characters in the story. I demonstrate how a systematic approach to exploring my subjectivity revealed aspects of my being as a research student that had potential for influence throughout the entirety of my experience. I argue that cognizance of my subjective I’s improved the quality of my research endeavour. Conclusion. The approach is offered for consideration by other research students as a means of exploring subjectivity. I argue that the resultant self-awareness can enhance the quality of the doctoral experience. The flexibility of the approach means it has transferability across a number of disciplines and cultural contexts. [ABSTRACT FROM AUTHOR]

The influence of the fatty acid composition of chylomicron remnant-like particles (CRLPs) on their uptake and induction of lipid accumulation in macrophages was studied. CRLPs containing triacylglycerol enriched in saturated, monounsaturated, n−6 or n−3 polyunsaturated fatty acids derived from palm, olive, corn or fish oil, respectively, and macrophages derived from the human monocyte cell line THP-1 were used. Lipid accumulation (triacylglycerol and cholesterol) in the cells was measured after incubation with CRLPs for 5, 24 and 48 h, and uptake over 24 h was determined using CRLPs radiolabelled with [3H]triolein. Total lipid accumulation in the macrophages was significantly greater with palm CRLPs than with the other three types of particle. This was mainly due to increased triacylglycerol concentrations, whereas changes in cholesterol concentrations did not reach significance. There were no significant differences in lipid accumulation after incubation with olive, corn or fish CRLPs. Palm and olive CRLPs were taken up by the cells at a similar rate, which was considerably faster than that observed with corn and fish CRLPs. These findings demonstrate that CRLPs enriched in saturated or monounsaturated fatty acids are taken up more rapidly by macrophages than those enriched in n−6 or n−3 polunsaturated fatty acids, and that the faster uptake rate results in greater lipid accumulation in the case of saturated fatty acid-rich particles, but not monounsaturated fatty acid-rich particles. Thus, dietary saturated fatty acids carried in chylomicron remnants may enhance their propensity to induce macrophage foam cell formation. [ABSTRACT FROM AUTHOR]

Over the past 50 years, there have been considerable changes both in how medical anthropologists view their relationship to topical public health and in how tropical public health professionals view the role of anthropologists. In particular, in recent decades critical currents have emerged from an anthropology of medicine, calling for an examination of biomedicine and its conceptualisation of public health. There are parallel debates in public health about a narrow disease-focused or broader socio-cultural approach to improving population health. Based on a review of the literature and a qualitative study of the views of public health professionals and anthropologists working in tropical public health, the data presented in this paper suggest that public health professionals remain unaware of many of the contributions anthropology could make to tropical public health theory and practice. However, the objectives of a critical social science are not dissimilar to those of the broader concept of public health. We suggest that there are grounds for optimism. For those of us concerned not just with disease but also with inequities in health, the challenge is to work towards a critical tropical public health which draws as much from social science as from biomedicine, in theory and practice. [ABSTRACT FROM AUTHOR]

Heat-shock protein (hsp)60/chaperonin 60 is a potent immunogen which has recently been claimed to have cell-signalling actions upon myeloid and vascular endothelial cells. The literature is controversial with different chaperonin 60 proteins producing different patterns of cellular activation and the ever-present criticism that activity is the result of bacterial contaminants. To clarify the situation we have cloned, expressed and purified to homogeneity the chaperonin 60 proteins fromChlamydia pneumoniae,Helicobacter pyloriand the human mitochondrion. These highly purified proteins were compared for their ability to stimulate human peripheral blood mononuclear cell (PBMC) cytokine synthesis and vascular endothelial cell adhesion protein expression. In spite of their significant sequence homology, theH. pyloriprotein was the most potent PBMC activator with the human protein the least potent. PBMC activation byC. pneumoniaeand human, but notH. pylori, chaperonin 60 was blocked by antibody neutralization of Toll-like receptor-4. TheC. pneumoniaechaperonin 60 was the most potent endothelial cell activator, with the human protein being significantly less active than bacterial chaperonin 60 proteins. These results have implications for the role of chaperonin 60 proteins as pathological factors in autoimmune and cardiovascular disease, and raise the possibility that each of these proteins may result in different pathological effects in such diseases. [ABSTRACT FROM AUTHOR]

Pancuronium bromide (PB) is used in neonates and pregnant women to induce limp, flaccid paralysis in order to allow mechanical ventilation during intensive care. Such non-depolarizing neuromuscular blocking drugs are administered to 0.1% of all human births in the UK. In this study, we examined PB effects on skeletal development in chick embryos. PB treatment produced skeletal deformities associated with significant reduction in longitudinal growth of all appendicular elements. This was associated with greater cartilage to bone ratios, indicating a preferential reduction in osteogenesis. PB also increased the incidence of knee joint flexion and tibiotarsal joint hyperextension. In addition to limb, spinal and craniofacial deformities, flaccid immobility appears to convert the normal geometric pattern of weight gain to a simple arithmetic accretion. This novel study highlights the potentially harmful effects of pharmacologically induced flaccid immobility on chick embryonic skeletal development. Whilst in ovo avian development clearly differs from human, our findings may have implications for the fetus, premature and term neonate receiving such non-depolarizing neuromuscular blocking drugs. [ABSTRACT FROM AUTHOR]

Activation of the protein kinase Akt/PKB mediates VEGF-dependent endothelial cell survival and eNOS activation. Here we examined the role of PKC in mediating VEGF-induced Akt activation. The PKC inhibitors GF109203X and calphostin C inhibited VEGF-induced Akt activation. Rottlerin and Go6976, inhibitors with specificities for PKCδ and α, respectively, also strongly inhibited VEGF-induced Akt activation. VEGF-induced Akt activation was prevented by down-regulation of PKC induced by prolonged pretreatment with the phorbol ester, PMA. VEGF induced phosphorylation of PKCδ at Thr 505 in the activation loop, and this phosphorylation was inhibited by LY294002, suggesting that modulation of PKCδ activation by VEGF occurs distal to phosphatidylinositol 3′-kinase. PKC and PI3K inhibitors both strongly reduced the stimulation of branching tubulogenesis by VEGF in vitro. The finding that PKC mediates VEGF-induced Akt activation identifies a novel signal transduction pathway through which Akt can be regulated by growth factors acting through receptor protein tyrosine kinases, and indicates that PKC-mediated Akt activity may play an essential role in VEGF-stimulated angiogenesis. [Copyright &y& Elsevier]

The article reviews the book "Abjectly Boundless: Boundaries, Bodies and Health Work," edited by Trudy Rudge and Dave Holmes.