Under-reporting of foetal alcohol spectrum disorders: an analysis of hospital episode statistics

<p>Abstract</p> <p>Background</p> <p>Internationally, 0.97 per 1,000 live births are affected by foetal alcohol syndrome (FAS). However, prevalence intelligence has been limited in the UK, hindering the development of appropriate services. This analysis compares hospital admissions over time, between regions and with alcohol-related admissions for adult females to assess whether established patterns (such as the North experiencing elevated harms) can be identified.</p> <p>Methods</p> <p>A retrospective analysis of hospital admissions data (April 2002 to March 2008) for foetal alcohol spectrum disorder (FASD)-related conditions: foetal alcohol syndrome (dysmorphic) (n = 457); foetus and newborn affected by maternal use of alcohol (n = 157); maternal care for (suspected) damage to foetus from alcohol (n = 285); and 322,161 women admitted due to alcohol-related conditions.</p> <p>Results</p> <p>Whilst the rate of admission for alcohol-related conditions in women aged 15-44 years increased significantly by 41% between 2002/03 and 2007/08 (p < 0.0001), no such increases were seen in the numbers of FASD-related conditions (all p < 0.05). Established regional rates of admission for alcohol-related conditions in women aged 15-44 years old were not associated with admission for FASD-related conditions.</p> <p>Conclusions</p> <p>It would be expected that the North West and North East regions, known to have higher levels of alcohol harm would have higher levels of FASD-related conditions. However, this was not reflected in the incidence of such conditions, suggesting under-reporting. With incomplete datasets, intelligence systems are severely limited, hampering efforts to develop targeted interventions. Improvements to intelligence systems, practitioner awareness and screening are essential in tackling this.</p

Use of fake identification to purchase alcohol amongst 15-16 year olds: a cross-sectional survey examining alcohol access, consumption and harm

<p>Abstract</p> <p>Background</p> <p>Despite legislation and enforcement activities to prevent underage access to alcohol, underage individuals continue to be able to access alcohol and to do so at levels which put them at significant risk of alcohol-related harm.</p> <p>Methods</p> <p>An opportunistic survey of 15-16 year olds (n = 9,833) across North West England was used to examine alcohol consumption, methods of access and related harms experienced (such as regretted sex). Associations between these were analysed using chi square and logistic regression techniques.</p> <p>Results</p> <p>Over a quarter (28.3%) of 15-16 year old participants who drank reported having bought their own alcohol. One seventh (14.9%) of these owned at least one form of fake identification for which by far the most common purchase method was online. Logistic regression analyses showed that those who owned fake identification were significantly more likely to be male (AOR = 2.0; 95% CI = 1.7-2.5; P < 0.001) and to receive a higher personal weekly income (comparing those who received > £30 with those who received ≤ £10: AOR = 3.7; 95% CI = 2.9-4.9; P < 0.001). After taking into account differences in demographic characteristics and personal weekly income, ownership of fake identification was significantly associated with binge drinking (AOR = 3.5, 95% CI = 2.8-4.3; P < 0.001), frequent drinking (AOR = 3.0, 95% CI = 2.5-3.7; P < 0.001) and public drinking (AOR = 3.3, 95% CI = 2.5-4.1; P < 0.001) compared with those who did not own fake identification. Further, those who reported owning fake identification were significantly more likely to report experiencing a variety of alcohol-related harms such as regretted sex after drinking (chi square, all P < 0.001).</p> <p>Conclusions</p> <p>Young people (aged 15-16 years) who have access to fake identification are at a particularly high risk of reporting hazardous alcohol consumption patterns and related harm. Owning fake identification should be considered a risk factor for involvement in risky drinking behaviours. Information on these hazards should be made available to schools and professionals in health, social and judicial services, along with advice on how to best to work with those involved.</p

Parental knowledge of alcohol consumption : a cross sectional survey of 11-17 year old schoolchildren and their parents

Background: Developing timely and effective strategies for preventing alcohol misuse in young people is required in order to prevent related harms since, worldwide, alcohol consumption was associated with 320,000 deaths amongst 15–29 year olds in 2004. Providing guidance and advice to parents is essential if alcohol misuse is to be reduced. However, prevention of risky behaviours is hampered if parents are unaware of the risks involved. Methods: A cross-sectional school-based survey of parent–child dyads, simultaneously questioning 935 children aged 11–17 years old and their parent(s). Univariate and multivariate associations are reported between demography, alcohol behaviours and parental knowledge of their child’s alcohol consumption. Results: 41.1% (n = 384) of children reported drinking alcohol. Of these, 79.9% of their parents were aware of their child’s alcohol consumption. Children aged 11–14 years had over a twofold greater odds of consuming alcohol without parental knowledge compared with 15–17 year olds (AOR: 2.7, 95% CI: 1.3-5.7). Of parent–child dyads where the child reported consuming alcohol, 92.7% of parents reported that they had spoken to their child about alcohol at least once in the past three months, whereas 57.3% of their children reported that this had occurred. Children who consumed alcohol and whose parents did not know they drank alcohol were less likely to report having a parental discussion about alcohol in the last three months (AOR: 0.4, 95% CI: 0.1-1.0) or report lifetime receipt of at least one other parenting protective measure (AOR: 0.5, 95% CI: 0.2-0.9) compared with those children who drank alcohol with parental knowledge. Conclusions: Whilst only small numbers of young adolescents in our sample were drinking alcohol compared with older adolescents, those who did were more likely to do so without their parents’ knowledge. These two factors combined (drinking earlier and drinking without parental knowledge) could place children at risk of immediate harm. Further research is essential to identify whether public health strategies should be developed which could support parents to employ lifestyle parenting techniques even before the parent believes the child to be at risk

Cross-sectional measures and modelled estimates of blood alcohol levels in UK nightlife and their relationships with drinking behaviours and observed signs of inebriation

<p>Abstract</p> <p>Background</p> <p>Management of nightlife in UK cities focuses on creating safe places for individuals to drink. Little is known about intoxication levels as measuring total alcohol consumption on nights out is complicated by early evening interviews missing subsequent consumption and later interviews risking individuals being too drunk to recall consumption or participate at all. Here we assess mixed survey and modelling techniques as a methodological approach to examining these issues.</p> <p>Methods</p> <p>Interviews with a cross sectional sample of nightlife patrons (n = 214) recruited at different locations in three cities established alcohol consumption patterns up to the point of interview, self-assessed drunkenness and intended drinking patterns throughout the remaining night out. Researchers observed individuals' behaviours to independently assess drunkenness. Breath alcohol tests and general linear modelling were used to model blood alcohol levels at participants' expected time of leaving nightlife settings.</p> <p>Results</p> <p>At interview 49.53% of individuals regarded themselves as drunk and 79.43% intended to consume more alcohol before returning home, with around one in ten individuals (15.38% males; 4.35% females) intending to consume >40 units (equal to 400 mls of pure alcohol). Self-assessed drunkenness, researcher observed measures of sobriety and blood alcohol levels all correlated well. Modelled estimates for blood alcohol at time of going home suggested that 71.68% of males would be over 0.15%BAC (gms alcohol/100 mls blood). Higher blood alcohol levels were related to drinking later into the night.</p> <p>Conclusions</p> <p>UK nightlife has used substantive health and judicial resources with the aim of creating safer and later drinking environments. Survey and modelling techniques together can help characterise the condition of drinkers when using and leaving these settings. Here such methods identified patrons as routinely getting drunk, with risks of drunkenness increasing over later nights. Without preventing drunkenness and sales to intoxicated individuals, extended drinking hours can simply act as havens for drunks. A public health approach to nightlife is needed to better understand and take into account the chronic effects of drunkenness, the damages arising after drunk individuals leave city centres and the costs of people avoiding drunken city centres at night.</p

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

Regional Selection Acting on the OFD1 Gene Family

The OFD1 (oral-facial-digital, type 1) gene is implicated in several developmental disorders in humans. The X-linked OFD1 (OFD1X) is conserved in Eutheria. Knowledge about the Y-linked paralog (OFD1Y) is limited. In this study, we identified an OFD1Y on the bovine Y chromosome, which is expressed differentially from the bovine OFD1X. Phylogenetic analysis indicated that: a) the eutherian OFD1X and OFD1Y were derived from the pair of ancestral autosomes during sex chromosome evolution; b) the autosomal OFD1 pseudogenes, present in Catarrhini and Murinae, were derived from retropositions of OFD1X after the divergence of primates and rodents; and c) the presence of OFD1Y in the ampliconic region of the primate Y chromosome is an indication that the expansion of the ampliconic region may initiate from the X-degenerated sequence. In addition, we found that different regions of OFD1/OFD1X/OFD1Y are under differential selection pressures. The C-terminal half of OFD1 is under relaxed selection with an elevated Ka/Ks ratio and clustered positively selected sites, whereas the N-terminal half is under stronger constraints. This study provides some insights into why the OFD1X gene causes OFD1 (male-lethal X-linked dominant) and SGBS2 & JSRDs (X-linked recessive) syndromes in humans, and reveals the origin and evolution of the OFD1 family, which will facilitate further clinical investigation of the OFD1-related syndromes

The Big Drink Debate: perceptions of the impact of price on alcohol consumption from a large scale cross-sectional convenience survey in north west England

<p>Abstract</p> <p>Background</p> <p>A large-scale survey was conducted in 2008 in north west England, a region with high levels of alcohol-related harm, during a regional 'Big Drink Debate' campaign. The aim of this paper is to explore perceptions of how alcohol consumption would change if alcohol prices were to increase or decrease.</p> <p>Methods</p> <p>A convenience survey of residents (≥ 18 years) of north west England measured demographics, income, alcohol consumption in previous week, and opinions on drinking behaviour under two pricing conditions: low prices and discounts and increased alcohol prices (either 'decrease', 'no change' or 'increase'). Multinomial logistic regression used three outcomes: 'completely elastic' (consider that lower prices increase drinking and higher prices decrease drinking); 'lower price elastic' (lower prices increase drinking, higher prices have no effect); and 'price inelastic' (no change for either).</p> <p>Results</p> <p>Of 22,780 drinkers surveyed, 80.3% considered lower alcohol prices and discounts would increase alcohol consumption, while 22.1% thought raising prices would decrease consumption, making lower price elasticity only (i.e. lower prices increase drinking, higher prices have no effect) the most common outcome (62%). Compared to a high income/high drinking category, the lightest drinkers with a low income (adjusted odds ratio AOR = 1.78, 95% confidence intervals CI 1.38-2.30) or medium income (AOR = 1.88, CI 1.47-2.41) were most likely to be lower price elastic. Females were more likely than males to be lower price elastic (65% vs 57%) while the reverse was true for complete elasticity (20% vs 26%, P < 0.001).</p> <p>Conclusions</p> <p>Lower pricing increases alcohol consumption, and the alcohol industry's continued focus on discounting sales encourages higher drinking levels. International evidence suggests increasing the price of alcohol reduces consumption, and one in five of the surveyed population agreed; more work is required to increase this agreement to achieve public support for policy change. Such policy should also recognise that alcohol is an addictive drug, and the population may be prepared to pay more to drink the amount they now feel they need.</p

The dynamic cilium in human diseases

Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

PURPOSE: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. METHODS: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. RESULTS: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). CONCLUSION: The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field