Transcriptome analysis of cortical tissue reveals shared sets of downregulated genes in autism and schizophrenia.

Autism (AUT), schizophrenia (SCZ) and bipolar disorder (BPD) are three highly heritable neuropsychiatric conditions. Clinical similarities and genetic overlap between the three disorders have been reported; however, the causes and the downstream effects of this overlap remain elusive. By analyzing transcriptomic RNA-sequencing data generated from post-mortem cortical brain tissues from AUT, SCZ, BPD and control subjects, we have begun to characterize the extent of gene expression overlap between these disorders. We report that the AUT and SCZ transcriptomes are significantly correlated (P<0.001), whereas the other two cross-disorder comparisons (AUT-BPD and SCZ-BPD) are not. Among AUT and SCZ, we find that the genes differentially expressed across disorders are involved in neurotransmission and synapse regulation. Despite the lack of global transcriptomic overlap across all three disorders, we highlight two genes, IQSEC3 and COPS7A, which are significantly downregulated compared with controls across all three disorders, suggesting either shared etiology or compensatory changes across these neuropsychiatric conditions. Finally, we tested for enrichment of genes differentially expressed across disorders in genetic association signals in AUT, SCZ or BPD, reporting lack of signal in any of the previously published genome-wide association study (GWAS). Together, these studies highlight the importance of examining gene expression from the primary tissue involved in neuropsychiatric conditions-the cortical brain. We identify a shared role for altered neurotransmission and synapse regulation in AUT and SCZ, in addition to two genes that may more generally contribute to neurodevelopmental and neuropsychiatric conditions

If at first you don’t succeed, when should you try again? A prospective study of failed quit attempts and subsequent smoking cessation

Objective: To assess the association between likelihood of success of smoking cessation attempts and time since most recent attempt. / Methods: Prospective study of 823 smokers who reported a failed quit attempt in the last 12 months at baseline and ≥1 quit attempt over 6-month follow-up. The input variable was time in months between the end (and in an exploratory analysis, the start) of the most recent failed quit attempt reported retrospectively at baseline and start of the first attempt made during the 6-month follow-up period. The outcome variable was success in the latter quit attempt. / Results: Success rates for failed quitters who waited <3, 3–6, and 6–12 months between their failed quit attempt ending and making a subsequent quit attempt were 13.8%, 17.5%, and 19.0% respectively. After adjustment for covariates, the odds of cessation relative to those who made a subsequent quit attempt within 3 months were 1.42 (95%CI 0.79–2.55) and 1.52 (95%CI 0.81–2.86) for those who waited 3–6 and 6–12 months respectively before trying again. Bayes factors indicated the data were insensitive. The exploratory analysis showed the odds of cessation were 1.55 (95%CI 0.78–3.08), 1.92 (95%CI 0.94–3.92), and 2.47 (95%CI 1.04–5.83) greater for those with an interval of 3–6, 6–12, and 12–18 months respectively than those who tried again within 3 months. / Conclusions: While pre-planned analyses were inconclusive, exploratory analysis of retrospective reports of quit attempts and success suggested the likelihood of success of quit attempts may be positively associated with number of months since beginning a prior quit attempt. However, only the longest inter-quit interval examined (12–18 months) was associated with significantly greater odds of quit success relative to a <3 month interval in fully adjusted models; all other comparisons were inconclusive

A DNA delivery system targeting dendritic cells for use in immunization against malaria: a rodent model

DNA-based vaccination has emerged as a promising method of immunisation since the first demonstration of this technology. Improving the antibody responses is desirable for the protective efficacy and hence broad application of these vaccines. We examined the immunogenicity of a Plasmodium-based DNA vaccine that was targeted to antigen presenting cells by fusion to CTLA4. Fusion proteins comprising the extra-cellular domain of CTLA4, the hinge, CH2 and CH3 domains of human IgG1 and MSP-1 gene fragments were expressed in COS-7 cells. Three of the secreted proteins containing the mouse homologue of CTLA4 were shown to bind differently to the human B7-1 molecule expressed on THP-1 cells. Competition binding assays for two fusion proteins showed that binding was specific. When C57BL/6 mice were immunized with plasmids encoding the fusion proteins, antibodies against two denatured and one non-denatured MSP-1 gene fragments were successfully induced. The usefulness of this strategy in future studies of immunisaton against human malaria is discussed. Keywords: malaria, PbMSP-1, DNA vaccine, dendritic cells, rodent model Tanzania Health Research Bulletin Vol. 7(3) 2005: 142-14

Physical Activity, Sedentary Time, and Fatness in a Biethnic Sample of Young Children.

PURPOSE: To investigate associations of objectively-measured physical activity (PA) and sedentary time (ST) with adiposity in a predominantly bi-ethnic (South Asian and White British) sample of young children. METHODS: The sample included 333 children aged 11 months to 5 years who provided 526 cross-sectional observations for PA and body composition. Total PA volume (vector magnitude counts per minute (cpm)), daily time at multiple intensity levels (the cumulative time in activity >500 cpm, >1000 cpm, >1500 cpm and so on up to >6000 cpm), and time spent sedentary (6000 cpm: -1.57 (-3.01 to -0.12) mm per 20 min/d). Substitution of 20 min/d of ST with MVPA was associated with a lower sum of skinfolds (-0.77 (-1.46 to -0.084) mm). CONCLUSIONS: High light-intensity PA appears to be beneficial for body composition in young South Asian and White British children, but higher-intensity PA is more advantageous.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

The OPAL bugs count survey: exploring the effects of urbanisation and habitat characteristics using citizen science

Citizen science projects can gather datasets with observation counts and spatiotemporal coverage far in excess of what can easily be achieved using only professional scientists. However, there exists a potential trade-off between the number of participants and the quality of data gathered. The Bugs Count citizen science project had thousands of participants because of its few barriers to taking part, allowing participation by anyone in England with access to any area of outdoor space. It was designed to scope for both the effects of variation in local habitat and urbanisation on broad taxonomic groups of invertebrates, and the responses of six target ‘Species Quest’ species (Adalia bipunctata, Ocypus olens, Aglais urticae, Palomena prasina, Limax maximus, and Bombus hypnorum) to urbanisation. Participants were asked to search for invertebrates in three areas: ‘soft ground surfaces’, ‘human-made hard surfaces’, and ‘plants’ for 15 min per search. Participants recorded counts of taxa found and a range of environmental information about the survey area. Data samples were weighted according to identification experience and participant age and analysed using canonical correspondence analysis, and tests of observation homogeneity. Species Quest species showed species-specific relationships with urbanisation, but broad taxonomic groups did not show significant relationships with urbanisation. The latter were instead influenced by habitat type and microhabitat availability. The approach used demonstrates that citizen science projects with few barriers to entry can gather viable datasets for scoping broad trends, providing that the projects are carefully designed and analysed to ensure data quality

Developments since 2005 in understanding potential environmental impacts of CO2 leakage from geological storage

This paper reviews research into the potential environmental impacts of leakage from geological storage of CO2 since the publication of the IPCC Special Report on Carbon Dioxide Capture and Storage in 2005. Possible impacts are considered on onshore (including drinking water aquifers) and offshore ecosystems. The review does not consider direct impacts on man or other land animals from elevated atmospheric CO2 levels. Improvements in our understanding of the potential impacts have come directly from CO2 storage research but have also benefitted from studies of ocean acidification and other impacts on aquifers and onshore near surface ecosystems. Research has included observations at natural CO2 sites, laboratory and field experiments and modelling. Studies to date suggest that the impacts from many lower level fault- or well-related leakage scenarios are likely to be limited spatially and temporarily and recovery may be rapid. The effects are often ameliorated by mixing and dispersion of the leakage and by buffering and other reactions; potentially harmful elements have rarely breached drinking water guidelines. Larger releases, with potentially higher impact, would be possible from open wells or major pipeline leaks but these are of lower probability and should be easier and quicker to detect and remediate

Effectiveness of training stop-smoking advisers to deliver cessation support to the UK national proposed standard versus usual care in Malaysia: a two-arm cluster randomised controlled trial

AIMS: To assess the effectiveness of training stop smoking services providers in Malaysia to deliver support for smoking cessation based on the UK National Centre for Smoking Cessation and Training (NCSCT) standard treatment programme compared with usual care. DESIGN: Two‐arm cluster‐randomized controlled effectiveness trial across 19 sites with follow‐up at 4‐week, 3‐month, and 6‐month. SETTING: Stop smoking services operating in public hospitals in Malaysia. PARTICIPANTS: Five hundred and two smokers [mean ± standard deviation (SD), age 45.6 (13.4) years; 97.4% male] attending stop smoking services in hospital settings in Malaysia: 330 in 10 hospitals in the intervention condition and 172 in nine hospitals in the control condition. INTERVENTION AND COMPARATOR: The intervention consisted of training stop‐smoking practitioners to deliver support and follow‐up according to the NCSCT Standard Treatment Programme. The comparator was usual care (brief support and follow‐up). MEASUREMENTS: The primary outcome was continuous tobacco smoking abstinence up to 6 months in smokers who received smoking cessation treatment, verified by expired‐air carbon monoxide (CO) concentration. Secondary outcomes were continuous CO‐verified tobacco smoking abstinence up to 4 weeks and 3 months. RESULTS: Follow‐up rates at 4 weeks, 3 months and 6 months were 80.0, 70.6 and 53.3%, respectively, in the intervention group and 48.8, 30.8 and 23.3%, respectively, in the control group. At 6‐month follow‐up, 93 participants in the intervention group and 19 participants in the control group were abstinent from smoking, representing 28.2 versus 11.0% in an intention‐to‐treat (ITT) analysis assuming that participants with missing data had resumed smoking, and 52.8 versus 47.5% in a follow‐up‐only (FUO) analysis. Unadjusted odds ratios (accounting for clustering) were 5.04, (95% confidence interval (CI) = 1.22–20.77, P = 0.025) and 1.70, (95% CI = 0.25–11.53, P = 0.589) in the ITT and FUO analyses, respectively. Abstinence rates at 4 week and 3 month follow‐ups were significantly higher in the intervention versus control group in the ITT but not the FUO analysis. CONCLUSIONS: On an intention‐to‐treat analysis with missing‐equals‐smoking imputation, training Malaysian stop smoking service providers in the UK National Centre for Smoking Cessation and Training standard treatment programme appeared to increase 6 month continuous abstinence rates in smokers seeking help with stopping compared with usual care. However, the effect may have been due to increasing follow‐up rates

Identifying Factors to Improve Oral Cancer Screening Uptake: A Qualitative Study

Aims: To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake. Methods: Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside. Results: There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is ‘inaccessible ’ on a physical and psychological level, costly, a ‘tooth specialist ’ not a ‘mouth specialist’, and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer. Conclusions: The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a ‘‘health’ ’ screening setting as opposed to a ‘‘dental’ ’ setting for such checks

Anomalous structure in the single particle spectrum of the fractional quantum Hall effect

The two-dimensional electron system (2DES) is a unique laboratory for the physics of interacting particles. Application of a large magnetic field produces massively degenerate quantum levels known as Landau levels. Within a Landau level the kinetic energy of the electrons is suppressed, and electron-electron interactions set the only energy scale. Coulomb interactions break the degeneracy of the Landau levels and can cause the electrons to order into complex ground states. In the high energy single particle spectrum of this system, we observe salient and unexpected structure that extends across a wide range of Landau level filling fractions. The structure appears only when the 2DES is cooled to very low temperature, indicating that it arises from delicate ground state correlations. We characterize this structure by its evolution with changing electron density and applied magnetic field. We present two possible models for understanding these observations. Some of the energies of the features agree qualitatively with what might be expected for composite Fermions, which have proven effective for interpreting other experiments in this regime. At the same time, a simple model with electrons localized on ordered lattice sites also generates structure similar to those observed in the experiment. Neither of these models alone is sufficient to explain the observations across the entire range of densities measured. The discovery of this unexpected prominent structure in the single particle spectrum of an otherwise thoroughly studied system suggests that there exist core features of the 2DES that have yet to be understood.Comment: 15 pages, 10 figure

Multilevel models of age-related changes in facial shape in adolescents

Here we study the effects of age on facial shape in adolescents by using a method called multilevel principal components analysis (mPCA). An associated multilevel multivariate probability distribution is derived and expressions for the (conditional) probability of age-group membership are presented. This formalism is explored via Monte Carlo (MC) simulated data in the first dataset; where age is taken to increase the overall scale of a three-dimensional facial shape represented by 21 landmark points and all other “subjective” variations are related to the width of the face. Eigenvalue plots make sense and modes of variation correctly identify these two main factors at appropriate levels of the mPCA model. Component scores for both single-level PCA and mPCA show a strong trend with age. Conditional probabilities are shown to predict membership by age group and the Pearson correlation coefficient between actual and predicted group membership is r = 0.99. The effects of outliers added to the MC training data are reduced by the use of robust covariance matrix estimation and robust averaging of matrices. These methods are applied to another dataset containing 12 GPA-scaled (3D) landmark points for 195 shapes from 27 white, male schoolchildren aged 11 to 16 years old. 21% of variation in the shapes for this dataset was accounted for by age. Mode 1 at level 1 (age) via mPCA appears to capture an increase in face height with age, which is consistent with reported pubertal changes in children. Component scores for both single-level PCA and mPCA again show a distinct trend with age. Conditional probabilities are again shown to reflect membership by age group and the Pearson correlation coefficient is given by r = 0.63 in this case. These analyses are an excellent first test of the ability of multilevel statistical methods to model age-related changes in facial shape in adolescents