Loneliness in young people: a multilevel exploration of social ecological influences and geographic variation.

BACKGROUND: Loneliness is a growing public health concern, yet little is known about loneliness in young people. The current study aimed to identify social ecological factors related to loneliness and examine the extent to which geographic region may account for differences in loneliness. METHODS: The data come from a cross-sectional sample of 6503 young people living in the UK. Loneliness was measured using the UCLA 3-item scale. Bivariate analyses were used to test associations between each predictor and loneliness. Multilevel models were used to identify key social ecological factors related to loneliness, and the extent to which loneliness may vary across geographic regions (local authority districts). RESULTS: Sociodemographic, social, health and well-being, and community factors were found to be associated with loneliness. Geographic region was associated with 5-8% of the variation in loneliness. The effect of gender, sexual orientation and minority ethnic background on loneliness differed across regions. CONCLUSIONS: This is the first study to highlight modifiable social and community factors related to youth loneliness, and individual vulnerabilities, such as poor mental well-being. Results related to geographic differences suggest that local-level initiatives may be most appropriate in tackling loneliness, rather than wider, less contextualized national efforts.

Genetic rescue, the greater prairie chicken and the problem of conservation reliance in the Anthropocene.

A central question in conservation is how best to manage biodiversity, despite human domination of global processes (= Anthropocene). Common responses (i.e. translocations, genetic rescue) forestall potential extirpations, yet have an uncertain duration. A textbook example is the greater prairie chicken (GRPC: Tympanuchus cupido pinnatus), where translocations (1992-1998) seemingly rescued genetically depauperate Illinois populations. We re-evaluated this situation after two decades by genotyping 21 microsatellite loci from 1831 shed feathers across six leks in two counties over 4 years (2010-2013). Low migration rates (less than 1%) established each county as demographically independent, but with declining-population estimates (4 year average N = 79). Leks were genetically similar and significantly bottlenecked, with low effective population sizes (average Ne = 13.1; 4 year Ne/N = 0.166). Genetic structure was defined by 12 significantly different family groups, with relatedness r = 0.31 > half-sib r = 0.25. Average heterozygosity, indicating short-term survival, did not differ among contemporary, pre- and post-translocated populations, whereas allelic diversity did. Our results, the natural history of GRPC (i.e. few leks, male dominance hierarchies) and its controlled immigration suggest demographic expansion rather than genetic rescue. Legal protection under the endangered species act (ESA) may enhance recovery, but could exacerbate political-economic concerns on how best to manage 'conservation-reliant' species, for which GRPC is now an exemplar.

Exercise testing and training in people with Huntington's disease.

OBJECTIVE: To explore exercise response in people with Huntington's disease (HD). DESIGN: Experimental observational study with a randomly allocated subgroup before/after interventional study. SETTING: Community. SUBJECTS: People with HD (n=30) and a healthy comparator group (n=20). Thirteen people from the HD group were randomly allocated to an exercise training program. MAIN MEASURES: Heart rate (HR) and perceived exertion on the Borg-CR10 scale (RPE) during a submaximal cycle ergometer exercise test (three minute unloaded and nine minute 65%-75%HRmaximum phase). Expired air and lactate measures were available for 8 people with HD during the exercise. INTERVENTION: A 12 week gym and home walking exercise programme (n=13). RESULTS: People with HD achieved a lower work rate at nine minutes (82±42(0-195) v 107±35(50 -185) Watts (p<0.05)), but higher RPE at both three (3±2(0-7) v 1±1(0-4)) and nine minutes (7±3(1-10) v 5± 2(2-9)) both p<0.01, compared to the healthy group and did not achieve a steady state HR during unloaded cycling. People with HD also demonstrated higher than expected lactate at three 2.5±2.5(1.1-8)mmo.L-1 and nine 3.8±1.9(1.2-6.6)mmo.L-1 minutes and respiratory exchange ratio at three 0.78±0.03 (0.74-0.81) and nine minutes 0.94±0.11(0.81-1.15). After exercise training there were no changes observed in HR or RPE responses during the exercise test. CONCLUSIONS: There was a large variability in the observed metabolic and physiological responses to exercise in people with HD. The observed exercise responses suggest that altered exercise prescription parameters may be required for people with HD and that exercise response and factors' affecting this requires further investigation.

Identification of children in the first four years of life for early treatment for otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) is the most common cause of acquired hearing loss in childhood and has been associated with delayed language development and behavioural problems. This condition has a point-prevalence of about 20% at the age of two years, a time of rapid language development. It is most often asymptomatic. Effective treatment exists for clearing effusions. Some have argued, therefore, that children should be screened and treated early if found to have clinically important OME. However, there is a high rate of spontaneous resolution of effusions and, for some children, effusions may represent a physiological response that does not reduce hearing significantly or impact negatively on language development or behaviour. Previous reviews of the effect of screening and treatment have included studies using non-randomised designs. OBJECTIVES: The aim of this review was to assess evidence from randomised controlled trials about the effect, on language and behavioural outcomes, of screening and treating children with clinically important OME in the first four years of their life. The focus was on the first four years of life because this is the time of most rapid language development. The consequences of hearing loss are likely to be most serious during this time. In addition, children of this age are least likely to be able to report or seek help for impaired hearing, particularly if these problems have a slow onset and are subtle. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006) and EMBASE (1974 to 2006) in February 2002, and again in January 2006, and the reference lists of all studies. We also contacted the first authors of the studies we included in the original review. SELECTION CRITERIA: 1. Randomised controlled trials evaluating interventions for OME among children with OME identified through screening.2. Comparison of outcomes for children randomised to be screened for OME and outcomes for children who were not randomised to be screened for OME. DATA COLLECTION AND ANALYSIS: Four authors independently extracted data and assessed trial quality, two in the original review and two for the update. MAIN RESULTS: We identified no trials comparing outcomes for children randomised to be screened for OME with outcomes for children who were not randomised to be screened for OME. We identified three trials evaluating interventions for OME among children with OME identified through screening, one of which generated three published studies. These were trials of treatment in children identified through screening rather than trials of treatment programs. From these trials, we found no evidence of clinically important benefit in language development from screening and treating children with clinically important OME. AUTHORS' CONCLUSIONS: The identified randomised trials do not show an important benefit on language development and behaviour from screening of the general population of asymptomatic children in the first four years of life for OME. However, these trials were all conducted in developed countries. Evidence generated in the developed world, where children may enjoy better nutrition, better living conditions and less severe and different infections may not be applicable to children in developing countries. The screening aspect of some of these studies was aimed primarily at identifying suitable children in whom to evaluate the effects of treatment, rather than to evaluate the effects of screening programs. Younger children and children with milder disease may have been included in these treatment trials compared to children who are offered treatment in pragmatic settings.

Young people's experiences of growing up in a family affected by Huntington's disease.

Previous research and clinical experience suggest that Huntington's disease (HD) can considerably affect family life, particularly for young people (YP) at risk. The goal of this study was to describe the experiences of YP from families affected by HD. YP were identified through the regional genetics clinic and the Scottish Huntington's Association. In-depth interviews were used to explore YP's experiences of finding out about HD in the family; perceptions of their own risk; caring activities; protective or risk factors; and the impact of HD on relationships with siblings, parents, extended family members, and the wider community. Thirty-three YP between the ages of 9 and 28 years were interviewed. A qualitative thematic analysis was undertaken. The analysis revealed four main themes: YP as carers, the worried well, those who cope, and those at risk/in need. These themes highlight the varied experience of growing up in a family affected by HD. Whilst some YP successfully coped, others experienced considerable problems and were at risk of physical and/or emotional harm. In understanding why some cope better than others, our findings suggest protective and risk factors within these themes. In particular, participants who grew up knowing about HD from an early age seemed to cope better.

Cannabis use, cognitive performance and mood in a sample of workers.

There are well documented acute and chronic effects of cannabis use on mental functioning. However, less is known about any effects on cognition within the context of work and everyday life. The aim of the study was to examine any association between cannabis use and cognitive performance, mood and human error at work. Cannabis users and controls completed a battery of laboratory based computer tasks measuring mood and cognitive function pre- and post-work at the start and end of a working week. They also completed daily diaries reporting their work performance. Cannabis use was associated with impairment in both cognitive function and mood, though cannabis users reported no more workplace errors than controls. Cannabis use was associated with lower alertness and slower response organization. In addition, users experienced working memory problems at the start, and psychomotor slowing and poorer episodic recall at the end of the working week. This pattern of results suggests two possible effects. First a 'hangover'-type effect which may increase with frequency of use. Second a subtle effect on cognitive function, perhaps more apparent under cognitive load and/or fatigue, which may increase with more prolonged use. The results also highlight the importance of the timing of testing within the context and routine of everyday life.

A community based investigation of the association between cannabis use, injuries and accidents.

There are well documented acute and chronic effects of cannabis use. However, less is known about any effects on safety within the context of work and everyday life. The aim of the study was to examine any association between cannabis use and injuries and accidents. A postal questionnaire survey was conducted among people selected at random from the electoral registers of Cardiff and Merthyr Tydfil. Cannabis use was associated with both minor injuries and accidents, particularly among those with high levels of other associated risk factors. Cannabis use was associated with a significant detrimental impact on safety. It is possible that this is linked to an amplification of other risk factors associated with accidents and injuries. This has potentially wide reaching implications particularly in the context of other work and lifestyle characteristics.

Psychotropic medication use and accidents, injuries and cognitive failures.

BACKGROUND: Psychotropic medication has the potential to impair psychomotor and cognitive function, and several medications have well documented links to increased accident and injury susceptibility. Those developed more recently have many fewer side effects. However, there is little work examining any association between psychotropic medication use and safety within the context of other demographic, health and lifestyle factors. AIMS: To examine and compare any associations between psychotropic medication use (including benzodiazepines, tricyclics and SSRIs) and accidents, injuries and cognitive failures in a community sample. METHODS: A postal questionnaire survey was conducted among people selected at random from the electoral registers of Cardiff and Merthyr Tydfil. RESULTS: Psychotropic medication use was associated with accidents, injuries and cognitive failures, particularly among those who already had higher levels of other risk factors and/or continuing mental health problems. CONCLUSIONS: The well established associations between accidents and injuries and older psychotropic medications were replicated. SSRIs, however, were relatively safer. The study also highlighted the need to consider any effect of psychotropic medication within the context of both mental health status and other factors.

Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.

We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.

Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene.

In this report, we describe the clinical and neuropathological features of a case of familial frontotemporal dementia (FTD), with onset at 58 years of age and disease duration of 10 years, associated with a novel mutation, Q336R, in the tau gene (tau). In vitro studies concerning the properties of tau proteins bearing this mutation, with respect to microtubule assembly and tau filament aggregation, are reported. Clinically, the patient showed alterations in memory, language and executive functions and marked behavioural change consistent with FTD, although the extent of memory impairment was more than is characteristic of FTD. At autopsy, there was degeneration of the frontal and temporal lobes associated with the presence of hyperphosphorylated tau proteins in swollen (Pick) cells and intraneuronal inclusions (Pick bodies). By immunohistochemistry, the Pick bodies contained both 3-repeat and 4-repeat tau proteins although, because no fresh tissues were available for analysis, the exact isoform composition of the aggregated tau proteins could not be determined. Neurons within frontal cortex contained neurofibrillary tangle-like structures, comprising both straight and twisted tubules, or Pick bodies in which the filaments were short and randomly orientated. In vitro, and in common with other tau missense mutations, Q336R caused an increase in tau fibrillogenesis. However, in contrast to most other tau missense mutations, Q336R increased, not decreased, the ability of mutant tau to promote microtubule assembly. Nonetheless, this latter functional change may likewise be detrimental to neuronal function by inducing a compensatory phosphorylation that may yield increased intracellular hyperphosphorylated tau species that are also liable to fibrillize. We believe the mutation is indeed pathogenic and disease causing and not simply a coincidental rare and benign polymorphism. Since this mutation is segregating with the FTD clinical and neuropathological phenotype, it has not been found in unaffected individuals and it has novel functional properties in vitro which are likely to be detrimental to neuronal function in vivo.

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners. The interviews confirmed that the issue of disclosure was a problem for some, and that there were generic communication issues common to both groups. Telling family members about genetic risk was generally seen as a family responsibility and family structures, dynamics and 'rules' influenced disclosure decisions. A sense of responsibility towards younger generations was also important. The level of certainty felt by a person in relation to his or her own risk estimate also influenced what he or she could tell other family members. Communication within a family about genetic risk is a complex issue and is influenced by both pre-existing familial and cultural factors and individuals' responses to risk information. If genetic counsellors understood how these factors operate in individual families they might be able to identify effective strategies to promote considered decisions and prevent unnecessary emotional distress.

The Bristol Stress and Health Study: accidents, minor injuries and cognitive failures at work.

BACKGROUND: Accidents and injuries at work account for several million working days lost each year. Cognitive failures (problems of memory, attention or action) can lead to accidents and injuries in certain contexts. AIM: This work describes the prevalence and associations of workplace accidents, minor injuries and cognitive failures reported by respondents to a follow-up postal questionnaire as part of the community-based Bristol Stress and Health Study. METHODS: Postal questionnaires were sent to 4673 people who participated in the first phase of the study (in which questionnaires were sent to individuals selected at random from the electoral roll). RESULTS: Four per cent of workers reported an accident at work, 8% reported quite or very frequent minor injuries and 13% reported quite or very frequent cognitive failures. Accidents at work were associated with being male, smoking and higher negative job characteristics. Respondents reported workplace accidents at a level similar to the overall UK rate. Accidents and minor injuries, and minor injuries and cognitive failures, shared common associations and all three outcomes were associated with each other. CONCLUSION: Information about cognitive failures is important in the study of accidents and injuries at work. In addition, negative job characteristics represent part of the context in which human error is translated into injury.

Differential deficits in expression recognition in gene-carriers and patients with Huntington's disease.

Previous studies in symptomatic patients and asymptomatic gene-carriers of Huntington's disease (HD) reported a differential deficit in the recognition of facial expressions of disgust. This impairment may point to involvement of the basal ganglia in the recognition of disgust. In this study, we compared the performance of 20 patients with symptoms of HD, 20 gene-carriers of HD and 20 healthy controls on two tests of facial expressions in order to further investigate the role of the basal ganglia in disgust recognition. Recognition of fear, rather than disgust, was most severely impaired in the patients, who were also impaired at recognising expressions of anger, disgust and sadness. Direct testing for a differential deficit in disgust at the group level (and at the level of individual HD cases) revealed that the patients were in fact significantly more impaired on the other negative expressions than on disgust. The gene-carriers were not impaired on any expression, although there was a trend for the gene-carriers to be poorer at recognising fearful faces than the controls. We argue that the expression recognition performance of the patients and gene-carriers simply reflects differences in task difficulty, rather than dysfunction of any mechanisms dedicated to specific emotions. In contrast to previous studies in patients or gene-carriers of HD, our findings provide no evidence for a role of the basal ganglia in the recognition of disgust and cast doubt on whether results from HD patients and gene-carriers can be used in support of a double dissociation between recognition of disgust and fear.

Breast cancer in two sisters with Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder causing progressive ataxia and dysarthria. We report two sisters who had breast cancer aged 39 years and 42 years and who both developed a late onset form of FRDA with onset of neurological symptoms in their thirties. We discuss whether there may be an association between the late onset form of FRDA and malignancy.

Additional glomangioma families link to chromosome 1p: no evidence for genetic heterogeneity.

Venous malformations are a common abnormality of the vasculature that may occur sporadically or, more rarely, as an autosomal dominant trait. One familial form of venous malformations has previously been linked to chromosome 9p. Mutations in the gene encoding Tie2, an endothelial specific receptor tyrosine kinase, have been identified in four different families. Glomangiomas are a subtype of venous malformations with glomus cell involvement. These cutaneous lesions can be inherited as an autosomal dominant disease with reduced penetrance and variable expressivity. We present evidence of linkage to chromosome 1p21-1p22 using four new glomangioma families, with a combined maximum two-point lod score of 7.32 at marker D1S2804. Markers D1S2129 and D1S2881 define the 24-cM linkage interval determined by recombination within affected individuals. A recent report also showed linkage of the glomangioma locus to chromosome 1p. A total of 9 families now map to this region, suggesting a decreased likelihood of locus heterogenity in familial glomangiomas. Investigation of candidate genes within the interval should provide new insights into lesion formation in inherited venous malformations.

Managing a sound industrial radiography radiation safety program.

This article was developed to provide new radiation safety officers with the basic information needed for ensuring safety, security, and control of industrial radiography sources and to discuss licensing requirements and other information pertaining to the management of radiation safety programs associated with these sources.

A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo-in vitro correlations.

An in vitro model of the rat nasal cavity has been used to compare the responses of nasal tissues in vitro, using loss of intracellular ATP and potassium as indices of toxicity, with the pathological changes occurring following in vivo exposure to four test compounds. Turbinates were incubated in vitro with the test compounds for 4 h, for 24 h or for 4 h followed by 20 h in fresh medium. Titanium dioxide caused little or no loss of ATP in either olfactory epithelium (OE) or respiratory epithelium (RE). Sodium carbonate decreased olfactory, but not respiratory ATP, while acetic acid and 3-methylindole markedly decreased ATP in both tissues. Intracellular potassium concentrations were generally affected to a lesser degree. In vivo, no morphological changes were observed in the nasal cavity following inhalation exposure to either titanium dioxide or sodium carbonate. Inhalation of acetic acid resulted in a very focal lesion in the RE of the dorsal meatus of level 1, while administration of 3-methylindole by intraperitoneal injection caused severe degeneration of OE. In further experiments olfactory turbinates were exposed to a range of concentrations (0-100 mM) of sodium carbonate, acetic acid and 3-methylindole for 4 h and ATP concentrations determined. Concentration-dependent decreases in ATP were observed for sodium carbonate and 3-methylindole, with EC(50) values estimated as 2.57 and 0.91 mM, respectively. Acetic acid only decreased ATP significantly at the 100-mM concentration. In summary, this in vitro model has predicted the nasal toxicity of several compounds, including both direct-acting agents (sodium carbonate, acetic acid) and one requiring metabolic activation (3-methylindole). However, the lack of airflow-dependent dosimetry, results in some lack of discrimination between the different regions of the nasal cavity and may make this model overly sensitive.