Optimal modelling of hearing impairment in middle age in relation to hearing in childhood as measured by audiograms

NCDS (National Child Development Survey) data include detailed audiograms at childhood ages 7,11,16 years and a ‘cut down’ audiogram at 45 years(frequencies 1 and 4 kHz only). A range of models relating data in childhood to adulthood is examined. Hearing losses at all childhood ages contribute independently and with comparable relationships to adult hearing loss: such models should include adjustments at all ages and at all frequencies in combination. This is possible through polynomial contrasts between frequencies at each age. Models which use the logarithm of the adult hearing measure as dependent variable are compared with those which use the raw score. Residuals from raw score models are found to have unacceptable distributional properties which are avoided by models of the log hearing loss. However, care needs to be taken in the interpretation of the coefficients in these models which can be easily transformed into an additive contribution due to the effects of further explanatory variables at specified values of existing variables. For categorical variables such as gender this will be a particular category and for continuous variables, such as childhood hearing, usually the mean. A range of multiple imputation models is compared with a complete case analysis. The complete case analysis excludes more than half of the data in models. In these cases I recommend the use of multiple imputation models. These models are can be estimated using recent macros in ‘off-the-peg’ statistical software (e.g. Mice in STATA). Mixed-effects and latent trajectory growth models are alternatives to the conditional models used here. These allow each individual to have a unique (growth) trajectory over time. Their advantages are limited in the case of these data due to the concentration of hearing loss data in childhood resulting from the absence of measurements of hearing loss in early adulthoo

Used infant mattresses and sudden infant death syndrome in Scotland: case-control study

<P>OBJECTIVE: To examine the proposition that a used infant mattress is associated with an increased risk of sudden infant death syndrome. DESIGN: Case-control study. SETTING: Scotland (population 5.1 million, with about 53 000 births a year).</P> <P>PARTICIPANTS: 131 infants who died of sudden infant death syndrome between 1 January 1996 and 31 May 2000 and 278 age, season, and obstetric unit matched control infants.</P> <P>MAIN OUTCOME MEASURES: Routine use of an infant mattress previously used by another child and place of last sleep.</P> <P>RESULTS: Routine use of an infant mattress previously used by another child was significantly associated with an increased risk of sudden infant death syndrome (multivariate odds ratio 3.07, 95% confidence interval 1.51 to 6.22). Use of a used infant mattress for last sleep was also associated with increased risk (6.10, 2.31 to 16.12). The association was significantly stronger if the mattress was from another home (4.78, 2.08 to 11.0) than if it was from the same home (1.64, 0.64 to 4.2).</P> <P>CONCLUSION: A valid significant association exists between use of a used infant mattress and an increased risk of sudden infant death syndrome, particularly if the mattress is from another home. Insufficient evidence is available to judge whether this relation is cause and effect.</P&gt

Am. J. Hum. Genet.

Thrombocytopenia–absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow’s milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR)

Social deprivation and exposure to health promotion. A study of the distribution of health promotion resources to schools in England

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 Chivu and ReidpathBACKGROUND: Area deprivation is a known determinant of health. It is also known that area deprivation is associated with lower impact health promotion. It is less well known, however, whether deprived areas are less responsive to health promotion, or whether they are less exposed. Using data from a national, school-based campaign to promote vaccination against the human papilloma virus (HPV), the relationship between area deprivation and exposure was examined. METHODS: Taking advantage of a health promotion campaign to provide information to schools about HPV vaccination, a cross sectional study was conducted to examine the relationship between area level, social deprivation, and take-up of (i.e., exposure to) available health promotion material. The sample was 4,750 schools across England, including government maintained and independent schools. The relationship between area deprivation and exposure was examined using bi- and multivariate logistic regression. RESULTS: It was found that schools in the least deprived quintile had 1.32 times the odds of requesting health promotion materials than schools in the most deprived areas (p = .01). This effect was independent of the school size, the type of school, and the geographic region. Conclusion The relationship between area deprivation and the impact of health promotion may be due, at least in part, to differential levels of exposure. The study was limited in scope, pointing to the need for more research, but also points to potentially important policy implications

The importance of both setting and intensity of physical activity in relation to non-clinical anxiety and depression

Physical activity is associated with good physical and mental health. Current recommendations suggest that people should achieve 30 minutes of moderate-intensity activity most days of the week to gain health benefits. This activity may be accumulated in leisure time, in active commuting, at work or in the home. Here we look at the cross-sectional relationship between physical activity and mental health as measured by the HADS anxiety and depression scores in a sample of 1,742 participants from a Scottish general population survey. The participants were men and women in three age cohorts aged around 24, 44 and 64 years who, in 1995, were interviewed face to face and also self-completed the HADS depression and anxiety scale. Respondents reported their levels of physical activity at work, in the home and in leisure time; the intensities of activity were also determined. Physical activity was related to depression scores but not to anxiety scores. There was no relationship between work physical activity and depression score. Among women, depression score increased with each additional episode of vigorous home activity. In both sexes, depression score decreased with each additional episode of vigorous leisure activity, but among men the decrease in depression score with moderate leisure activity was reversed if a lot of moderate activity was undertaken. We have found a variable relationship between depression scores and various settings for physical activity. Researchers, policymakers and practitioners who are interested in the relationship between physical activity and mental health should take into account the setting for activity as well as frequency, duration and intensity of activity

Neutropenia in Barth syndrome:characteristics, risks, and management

PURPOSE OF REVIEW: Barth syndrome (BTHS) is an X-linked disease characterized by defective remodeling of phospholipid side chains in mitochondrial membranes. Major features include neutropenia, dilated cardiomyopathy, motor delay and proximal myopathy, feeding problems, and constitutional growth delay. We conducted this review of neutropenia in BTHS to aid in the diagnosis of this disease, and to improve understanding of both the consequences of neutropenia and the benefits of treatment with granulocyte colony-stimulating factor (G-CSF). RECENT FINDINGS: In 88 patients with BTHS, neutropenia, that is, at least one count below 1.5 × 10/l, was detected in 74 (84%) and 44% had severe chronic neutropenia, with multiple counts below 0.5 × 10/l. The pattern of neutropenia varied between intermittent and unpredictable, chronic and severe, or cyclical with mathematically regular oscillations. Monocytosis, that is, monocytes more than 1.0 × 10/l, was observed at least once in 64 of 85 (75%) patients. G-CSF was administered to 39 of 88 patients (44%). Weekly average G-CSF doses ranged from 0.12 to 10.92 μg/kg/day (mean 1.16 μg/kg/day, median 1.16 μg/kg/day). Antibiotic prophylaxis was additionally employed in 21 of 26 neutropenic patients. Pretreatment bone marrow evaluations predominantly showed reduced myeloid maturation which normalized on G-CSF therapy in seven of 13 examined. Consistent clinical improvement, with reduced signs and symptoms of infections, was observed in response to prophylactic G-CSF ± prophylactic antibiotics. However, despite G-CSF and antibiotics, one adult patient died with multiple infections related to indwelling medical devices and gastrostomy site infection after 15.5 years on G-CSF and a pediatric patient required gastrostomy removal for recurrent abdominal wall cellulitis. SUMMARY: BTHS should be considered in any men with neutropenia accompanied by any of the characteristic features of this syndrome. Prophylaxis with G-CSF ± antibiotics prevents serious bacterial infections in the more severe neutropenic patients although infections remain a threat even in patients who are very compliant with therapy, especially in those with indwelling devices

Changes in the socio-demographic patterning of late adolescent health risk behaviours during the 1990s: analysis of two West of Scotland cohort studies

Background: Substance use and sexual risk behaviour affect young people's current and future health and wellbeing in many high-income countries. Our understanding of time-trends in adolescent health-risk behaviour is largely based on routinely collected survey data in school-aged adolescents (aged 15 years or less). Less is known about changes in these behaviours among older adolescents. Methods: We compared two cohorts from the same geographical area (West of Scotland), surveyed in 1990 and 2003, to: describe time-trends in measures of smoking, drinking, illicit drug use, early sexual initiation, number of opposite sex sexual partners and experience of pregnancy at age 18-19 years, both overall and stratified by gender and socioeconomic status (SES); and examine the effect of time-trends on the patterning of behaviours by gender and SES. Our analyses adjust for slight between-cohort age differences since age was positively associated with illicit drug use and pregnancy. Results: Rates of drinking, illicit drug use, early sexual initiation and experience of greater numbers of sexual partners all increased significantly between 1990 and 2003, especially among females, leading to attenuation and, for early sexual initiation, elimination, of gender differences. Most rates increased to a similar extent regardless of SES. However, rates of current smoking decreased only among those from higher SES groups. In addition, increases in 'cannabis-only' were greater among higher SES groups while use of illicit drugs other than cannabis increased more in lower SES groups. Conclusion: Marked increases in female substance use and sexual risk behaviours have implications for the long-term health and wellbeing of young women. More effective preventive measures are needed to reduce risk behaviour uptake throughout adolescence and into early adulthood. Public health strategies should reflect both the widespread prevalence of risk behaviour in young people as well as the particular vulnerability to certain risk behaviours among those from lower SES groups

Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging.

Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3 alpha (DNMT3A) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G > A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS), their mosaic father, and 15 TBRS patients with distinct pathogenic de novo DNMT3A variants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated as genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. These findings were most marked in a carrier of the AML-associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype-related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders: NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamental new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance, and determinants of biological aging in these growth disorders

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome