Can cohort data be treated as genuine panel data?

If repeated observations on the same individuals are not available it is not possible to capture unobserved individual characteristics in a linear model by using the standard fixed effects estimator. If large numbers of observations are available in each period one can use cohorts of individuals with common characteristics to achieve the same goal, as shown by Deaton (1985). It is tempting to analyze the observations on cohort averages as if they are observations on individuals which are observed in consecutive time periods. In this paper we analyze under which conditions this is a valid approach. Moreover, we consider the impact of the construction of the cohorts on the bias in the standard fixed effects estimator. Our results show that the effects of ignoring the fact that only a synthetic panel is available will be small if the cohort sizes are sufficiently large (100, 200 individuals) and if the true means within each cohort exhibit sufficient time variation

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BACKGROUND: Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. AIMS: To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. METHOD: The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. RESULTS: Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. CONCLUSIONS: A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour

A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses

Background: Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. Conclusions: Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1: 75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population

Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7

Background: Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. Results: We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C> T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. Conclusions: We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of the gene. The mutated gene implicates the extracellular matrix in the regular organization of chrondrocyte columns of the growth plate. Conservation of individual amino acids may not be necessary at the protein level but instead may reflect underlying conservation of nucleotide sequence that are required for efficient splicing

Predicting inpatient violence using an extended version of the Brøset-Violence-Checklist: instrument development and clinical application

BACKGROUND: Patient aggression is a common problem in acute psychiatric wards and calls for preventive measures. The timely use of preventive measures presupposes a preceded risk assessment. The Norwegian Brøset-Violence-Checklist (BVC) is one of the few instruments suited for short-time prediction of violence of psychiatric inpatients in routine care. Aims of our study were to improve the accuracy of the short-term prediction of violence in acute inpatient settings by combining the Brøset-Violence-Checklist (BVC) with an overall subjective clinical risk-assessment and to test the application of the combined measure in daily practice. METHOD: We conducted a prospective cohort study with two samples of newly admitted psychiatric patients for instrument development (219 patients) and clinical application (300 patients). Risk of physical attacks was assessed by combining the 6-item BVC and a 6-point score derived from a Visual Analog Scale. Incidents were registered with the Staff Observation of Aggression Scale-Revised SOAS-R. Test accuracy was described as the area under the receiver operating characteristic curve (AUC(ROC)). RESULTS: The AUC(ROC )of the new VAS-complemented BVC-version (BVC-VAS) was 0.95 in and 0.89 in the derivation and validation study respectively. CONCLUSION: The BVC-VAS is an easy to use and accurate instrument for systematic short-term prediction of violent attacks in acute psychiatric wards. The inclusion of the VAS-derived data did not change the accuracy of the original BVC

Joubert syndrome: genotyping a Northern European patient cohort

Joubert syndrome (JBS) is a rare neurodevelopmental disorder belonging to the group of ciliary diseases. JBS is genetically heterogeneous, with >20 causative genes identified to date. A molecular diagnosis of JBS is essential for prediction of disease progression and genetic counseling. We developed a targeted next-generation sequencing (NGS) approach for parallel sequencing of 22 known JBS genes plus 599 additional ciliary genes. This method was used to genotype a cohort of 51 well-phenotyped Northern European JBS cases (in some of the cases, Sanger sequencing of individual JBS genes had been performed previously). Altogether, 21 of the 51 cases (41%) harbored biallelic pathogenic mutations in known JBS genes, including 14 mutations not previously described. Mutations in C5orf42 (12%), TMEM67 (10%), and AHI1 (8%) were the most prevalent. C5orf42 mutations result in a purely neurological Joubert phenotype, in one case associated with postaxial polydactyly. Our study represents a population-based cohort of JBS patients not enriched for consanguinity, providing insight into the relative importance of the different JBS genes in a Northern European population. Mutations in C5orf42 are relatively frequent (possibly due to a Dutch founder mutation) and mutations in CEP290 are underrepresented compared with international cohorts. Furthermore, we report a case with heterozygous mutations in CC2D2A and B9D1, a gene associated with the more severe Meckel–Gruber syndrome that was recently published as a potential new JBS gene, and discuss the significance of this finding

Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions

Dynamic Interactive Social Cognition Training in Virtual Reality (DiSCoVR) versus Virtual Reality Relaxation (VRelax) for People With a Psychotic Disorder:A Single-Blind Multicenter Randomized Controlled Trial

BACKGROUND AND HYPOTHESIS: Social cognition training (SCT), an intervention for social cognition and social functioning, might be improved by using virtual reality (VR), because VR may offer better opportunities to practice in a potentially more realistic environment. To date, no controlled studies have investigated VR-SCT. This study investigated a VR-SCT, "DiSCoVR". We hypothesized that DiSCoVR would improve social cognition and social functioning. STUDY DESIGN: Participants were randomized to DiSCoVR (n = 41) or VR relaxation ('VRelax', n = 40), an active control condition, and completed 16 twice-weekly sessions. Three assessments (baseline, posttreatment, and 3-month follow-up) were performed by blinded assessors. The primary outcome was social cognition (emotion perception and theory of mind). Secondary outcomes included social functioning (measured with an interview and experience sampling), psychiatric symptoms, information processing, and self-esteem. Data were analyzed using mixed-models regression analysis. Treatment effects were evaluated by the time by condition interaction terms. STUDY RESULTS: No significant time by condition interactions were found for any of the outcome variables, indicating an absence of treatment effects. Between-group effect sizes ranged from negligible to moderate (Cohen's d < |0.53|). Main effects of time were found for several outcomes. CONCLUSIONS: These results suggest that DiSCoVR was not effective, possibly because of inadequate simulation of emotional expressions in VR. This lack of efficacy may indicate that current SCT protocols are relatively unsuitable for improving social functioning. Previous studies showed small to moderate effects on higher order social cognition, but the SCT approach may need critical reevaluation, as it may not sufficiently lead to functional improvement

The relationship between leadership, teamworking, structure, burnout and attitude to patients on acute psychiatric wards

Contains fulltext : 99818.pdf (publisher's version ) (Open Access)Background: Conflict (aggression, substance use, absconding, etc.) and containment (coerced medication, manual restraint, etc.) threaten the safety of patients and staff on psychiatric wards. Previous work has suggested that staff variables may be significant in explaining differences between wards in their rates of these behaviours, and that structure (ward organisation, rules and daily routines) might be the most critical of these. This paper describes the exploration of a large dataset to assess the relationship between structure and other staff variables. Methods: A multivariate cross-sectional design was utilised. Data were collected from staff on 136 acute psychiatric wards in 26 NHS Trusts in England, measuring leadership, teamwork, structure, burnout and attitudes towards difficult patients. Relationships between these variables were explored through principal components analysis (PCA), structural equation modelling and cluster analysis. Results: Principal components analysis resulted in the identification of each questionnaire as a separate factor, indicating that the selected instruments assessed a number of non-overlapping items relevant for ward functioning. Structural equation modelling suggested a linear model in which leadership influenced teamwork, teamwork structure; structure burnout; and burnout feelings about difficult patients. Finally, cluster analysis identified two significantly distinct groups of wards: the larger of which had particularly good leadership, teamwork, structure, attitudes towards patients and low burnout; and the second smaller proportion which was poor on all variables and high on burnout. The better functioning cluster of wards had significantly lower rates of containment events. Conclusion: The overall performance of staff teams is associated with differing rates of containment on wards. Interventions to reduce rates of containment on wards may need to address staff issues at every level, from leadership through to staff attitudes

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs