Structural, item, and test generalizability of the psychopathology checklist - revised to offenders with intellectual disabilities

The Psychopathy Checklist–Revised (PCL-R) is the most widely used measure of psychopathy in forensic clinical practice, but the generalizability of the measure to offenders with intellectual disabilities (ID) has not been clearly established. This study examined the structural equivalence and scalar equivalence of the PCL-R in a sample of 185 male offenders with ID in forensic mental health settings, as compared with a sample of 1,212 male prisoners without ID. Three models of the PCL-R’s factor structure were evaluated with confirmatory factor analysis. The 3-factor hierarchical model of psychopathy was found to be a good fit to the ID PCL-R data, whereas neither the 4-factor model nor the traditional 2-factor model fitted. There were no cross-group differences in the factor structure, providing evidence of structural equivalence. However, item response theory analyses indicated metric differences in the ratings of psychopathy symptoms between the ID group and the comparison prisoner group. This finding has potential implications for the interpretation of PCL-R scores obtained with people with ID in forensic psychiatric settings

Cohesin complex-associated holoprosencephaly

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly

A Prompt to the Web: The Media and Health Information Seeking Behaviour

UNLABELLED: OBJECTIVE, DESIGN, SETTING AND PARTICIPANTS: The objective was to investigate media influence on consumers' health related behaviours. A cross-sectional survey of randomly selected adults (18+ years) residing in the Hunter Region of New South Wales Australia was conducted. The sample was selected using a combination of the white pages and random digit dialling. MAIN OUTCOME MEASURES: The proportions of respondents who recalled seeing or hearing about conditions or treatments in the media over the 12 months prior to interview (August 2009-August 2010) and their subsequent health related behaviour. RESULTS: Although most survey participants reported seeking health information from their doctors, around two-thirds of survey participants (551, 68.8%) recalled hearing, seeing or reading about one or more medical conditions (total = 1097 instances) in the mainstream media over the past 12 months. Almost 40% of respondents (307, 38.4%) stated that they had looked for more information about a condition as a result of hearing about it in the media, and most used the internet (269, 87.4%). More than a quarter of respondents (215, 26.9%) indicated that they had asked their doctor about a condition they had heard about in the media. Around half of those who asked their doctor (109, 50.6%) reported that their inquiry resulted in them receiving treatment, of whom almost half (53, 48.3%) reported being prescribed a medicine. CONCLUSION: The survey results show that consumers become aware of medicines through traditional media and then to learn more often turn to the internet where quality of information may be poor

Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

BACKGROUND: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. RESULTS: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. CONCLUSION: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel

The re-identification risk of Canadians from longitudinal demographics

<p>Abstract</p> <p>Background</p> <p>The public is less willing to allow their personal health information to be disclosed for research purposes if they do not trust researchers and how researchers manage their data. However, the public is more comfortable with their data being used for research if the risk of re-identification is low. There are few studies on the risk of re-identification of Canadians from their basic demographics, and no studies on their risk from their longitudinal data. Our objective was to estimate the risk of re-identification from the basic cross-sectional and longitudinal demographics of Canadians.</p> <p>Methods</p> <p>Uniqueness is a common measure of re-identification risk. Demographic data on a 25% random sample of the population of Montreal were analyzed to estimate population uniqueness on postal code, date of birth, and gender as well as their generalizations, for periods ranging from 1 year to 11 years.</p> <p>Results</p> <p>Almost 98% of the population was unique on full postal code, date of birth and gender: these three variables are effectively a unique identifier for Montrealers. Uniqueness increased for longitudinal data. Considerable generalization was required to reach acceptably low uniqueness levels, especially for longitudinal data. Detailed guidelines and disclosure policies on how to ensure that the re-identification risk is low are provided.</p> <p>Conclusions</p> <p>A large percentage of Montreal residents are unique on basic demographics. For non-longitudinal data sets, the three character postal code, gender, and month/year of birth represent sufficiently low re-identification risk. Data custodians need to generalize their demographic information further for longitudinal data sets.</p

Generalized Connective Tissue Disease in Crtap-/- Mouse

Mutations in CRTAP (coding for cartilage-associated protein), LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1]) or PPIB (coding for Cyclophilin B [CYPB]) cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in α1(I) and α1(II) chains, there was also loss of 3Hyp at proline 986 in α2(V) chains. In contrast, at two of the known 3Hyp sites in α1(IV) chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V) collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin

De-identifying a public use microdata file from the Canadian national discharge abstract database

<p>Abstract</p> <p>Background</p> <p>The Canadian Institute for Health Information (CIHI) collects hospital discharge abstract data (DAD) from Canadian provinces and territories. There are many demands for the disclosure of this data for research and analysis to inform policy making. To expedite the disclosure of data for some of these purposes, the construction of a DAD public use microdata file (PUMF) was considered. Such purposes include: confirming some published results, providing broader feedback to CIHI to improve data quality, training students and fellows, providing an easily accessible data set for researchers to prepare for analyses on the full DAD data set, and serve as a large health data set for computer scientists and statisticians to evaluate analysis and data mining techniques. The objective of this study was to measure the probability of re-identification for records in a PUMF, and to de-identify a national DAD PUMF consisting of 10% of records.</p> <p>Methods</p> <p>Plausible attacks on a PUMF were evaluated. Based on these attacks, the 2008-2009 national DAD was de-identified. A new algorithm was developed to minimize the amount of suppression while maximizing the precision of the data. The acceptable threshold for the probability of correct re-identification of a record was set at between 0.04 and 0.05. Information loss was measured in terms of the extent of suppression and entropy.</p> <p>Results</p> <p>Two different PUMF files were produced, one with geographic information, and one with no geographic information but more clinical information. At a threshold of 0.05, the maximum proportion of records with the diagnosis code suppressed was 20%, but these suppressions represented only 8-9% of all values in the DAD. Our suppression algorithm has less information loss than a more traditional approach to suppression. Smaller regions, patients with longer stays, and age groups that are infrequently admitted to hospitals tend to be the ones with the highest rates of suppression.</p> <p>Conclusions</p> <p>The strategies we used to maximize data utility and minimize information loss can result in a PUMF that would be useful for the specific purposes noted earlier. However, to create a more detailed file with less information loss suitable for more complex health services research, the risk would need to be mitigated by requiring the data recipient to commit to a data sharing agreement.</p

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families