Prevalence estimation of intellectual disability using national administrative and household survey data: The importance of survey question specificity.

BACKGROUND: Variability in prevalence estimation of intellectual disability has been attributed to heterogeneity in study settings, methodologies, and intellectual disability case definitions. Among studies based on national household survey data specifically, variability in prevalence estimation has partly been attributed to the level of specificity of the survey questions employed to determine the presence of intellectual disability. SPECIFIC AIMS & METHOD: Using standardised difference scoring, and 'intellectual disability' survey data from the 2007 Northern Ireland Survey on Activity Limitation and Disability (NISALD) (N=23,689) and the 2011 Northern Ireland Census (N=1,770,217) the following study had two aims. First, we aimed to demonstrate the effects of survey question specificity on intellectual disability prevalence estimation. Second, we aimed to produce reliable estimates of the geographic variation of intellectual disability within private households in Northern Ireland while also assessing the socio-demographic, health-related and disability characteristics of this population. FINDINGS: Prevalence estimates generated using the more crudely classified intellectual disability Census data indicated a prevalence of 2% for the overall population, 3.8% for children aged between 0 and 15 years, and 1.5% for citizens aged 16 years or older. Intellectual disability prevalence estimates generated using the more explicitly defined 2007 NISALD data indicated a population prevalence of 0.5% for the overall population, 1.3% for children aged between 0 and 15 years, and 0.3% for citizens aged 16 years or older. The NISALD estimates were consistent with most recent international meta-analysis prevalence estimates. According to the NISALD data, the majority of those with an intellectual disability were male, lived outside Belfast, and experienced severe intellectual disability, with multiple comorbid health conditions. DISCUSSION: The current findings highlight the importance of survey question specificity in the estimation of intellectual disability prevalence and provide reliable prevalence estimates of intellectual disability in Northern Ireland. The findings also demonstrate the utility of administrative data for detecting and understanding intellectual disability, and inform recommendations on how to maximise use of future intellectual disability Census data.

Resistance to COVID-19 vaccination has increased in Ireland and the United Kingdom during the pandemic.

OBJECTIVES: Hesitance and resistance to COVID-19 vaccination poses a serious challenge to achieving adequate vaccine uptake in the general population. Cross-sectional data from the early months of the pandemic indicates that approximately one-third of adults in multiple nations are hesitant or resistant to a vaccine for COVID-19. Using longitudinal data, we tracked changes in attitudes to COVID-19 vaccination during the pandemic. STUDY DESIGN: This is a quantitative, longitudinal design. METHOD: Nationally representative samples of the adult general population of the Republic of Ireland (N = 1041) and the United Kingdom (N = 2025) were assessed for their attitudes towards COVID-19 vaccination at three points from March to August 2020. RESULTS: Statistically significant increases in resistance to COVID-19 vaccination were observed in Irish (from 9.5% to 18.1%) and British (from 6.2% to 10%) adults. CONCLUSION: Resistance to vaccination has significantly increased in two European nations as the pandemic has progressed. Growing resistance to COVID-19 vaccination will pose a challenge to public health officials responsible for ensuring sufficient vaccine coverage.

Anxiety and depression in the Republic of Ireland during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic in Ireland resulted in a nationwide quarantine on March 27, 2020. This study represents the first assessment of rates of anxiety and depression in the general population of Ireland during the pandemic. AIMS: Our first aim was to estimate the probable prevalence rates of generalized anxiety disorder (GAD) and depression and to identify sociodemographic risk factors associated with screening positive for GAD or depression. Our second aim was to determine if COVID-19 related anxiety was highest amongst those in society at greatest risk of morality from COVID-19. METHOD: Self-report data were collected from a nationally representative Irish sample (N = 1041) online between March 31 and April 5; the first week of the nationwide quarantine measures. Recognized cut-off scores on the GAD-7 and PHQ-9 were used to estimate rates of GAD and depression. Correlates of screening positive for GAD or depression were assessed using logistic regression analysis. RESULTS: GAD (20.0%), depression (22.8%) and GAD or depression (27.7%) was common. Screening positive for GAD or depression was associated with younger age, female sex, loss of income due to COVID-19, COVID-19 infection and higher perceived risk of COVID-19 infection. Citizens aged 65 and older had significantly higher levels of COVID-19 related anxiety than adults aged 18-34. CONCLUSIONS: Initial results from this multi-wave study monitoring changes in population anxiety and depression throughout the pandemic indicate that GAD and depression were common experiences in the population during the initial phase of the COVID-19 pandemic.

Trainee experience of 'out of hours' surgical working in the UK: A cross-sectional analysis.

BACKGROUND: Changes to working practices and increasing service demand have contributed to low morale amongst UK surgical trainees, with pressures particularly acute 'out of hours' (OOH). Surgeons may be expected to be 'on call' for multiple hospitals, or to provide remote consultations, yet healthcare systems may undermine their professional safety and patient care. This cross-sectional study sought to define the perceptions of UK-based Royal College of Surgeons of Edinburgh (RCSEd) affiliated trainees of OOH surgical care and training. METHODS: The RCSEd Trainees' Committee conducted a design-thinking exercise to produce an online questionnaire. Non-consultant grade RCSEd Members and Fellows were invited to participate. Quantitative data was analysed using descriptive statistics, and qualitative data was coded to identify emergent themes. RESULTS: One hundred and fifty-five surgeons participated. Of those surgeons working in multiple hospitals OOH (n = 16), many did not receive access cards (12[75%]) or site-specific induction (13[81%]), and 8(50%) were not confident in using local electronic investigation and records systems. Only 14/114 (12%) of the surgeons providing remote opinion had access to a consultation record system, and most perceived dissatisfaction with the system. Emergent themes from qualitative data revealed that trainee surgeons desire specific training in OOH working, concerns that OOH work experience is diminishing, and that hospital infrastructure such as IT and communications, rest facilities and catering were inadequate in facilitating safe care. CONCLUSIONS: The participants perceived that the systems supporting delivery of safe surgical care OOH were inadequate. Hospital leaders should ensure that systems minimise risk to staff and patients.

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

The population impact of common mental disorders and long-term physical conditions on disability and hospital admission.

BACKGROUND: Long-term physical conditions (LTCs) consume the largest share of healthcare budgets. Although common mental disorders (CMDs) and LTCs often co-occur, the potential impact of improved mental health treatment on severe disability and hospital admissions for physical health problems remains unknown. Method A cross-sectional study of 7403 adults aged 16-95 years living in private households in England was performed. LTCs were ascertained by prompted self-report. CMDs were ascertained by structured clinical interview. Disability was assessed using questions about problems with activities of daily living. Population impact and potential preventive gain were estimated using population-attributable fraction (PAF), and conservative estimates were obtained using 'treated non-cases' as the reference group. RESULTS: Of the respondents, 20.7% reported at least one LTC. The prevalence of CMDs increased with the number of LTCs, but over two-thirds (71.2%) of CMD cases in people with LTCs were untreated. Statistically significant PAFs were found for CMDs and recent hospital admission [13.5%, 95% confidence intervals (CI) 6.6-20.0] and severe disability (31.3%, 95% CI 27.1-35.2) after adjusting for LTCs and other confounders. Only the latter remained significant when using the most conservative estimate of PAF (21.8%, 95% CI 14.0-28.9), and this was reduced only slightly when considering only participants with LTCs (18.5%, 95% CI 7.9-27.9). CONCLUSIONS: Better treatments for CMDs in people with LTCs could achieve almost the same population health gain in terms of reducing severe disability as those targeted at the entire population. Interventions to reduce the prevalence of CMDs among people with LTCs should be part of routine medical care.

A hierarchy of distress and invariant item ordering in the General Health Questionnaire-12.

BACKGROUND: Invariant item ordering (IIO) is defined as the extent to which items have the same ordering (in terms of item difficulty/severity - i.e. demonstrating whether items are difficult [rare] or less difficult [common]) for each respondent who completes a scale. IIO is therefore crucial for establishing a scale hierarchy that is replicable across samples, but no research has demonstrated IIO in scales of psychological distress. We aimed to determine if a hierarchy of distress with IIO exists in a large general population sample who completed a scale measuring distress. METHODS: Data from 4107 participants who completed the 12-item General Health Questionnaire (GHQ-12) from the Northern Ireland Health and Social Wellbeing Survey 2005-6 were analysed. Mokken scaling was used to determine the dimensionality and hierarchy of the GHQ-12, and items were investigated for IIO. RESULTS: All items of the GHQ-12 formed a single, strong unidimensional scale (H=0.58). IIO was found for six of the 12 items (H-trans=0.55), and these symptoms reflected the following hierarchy: anhedonia, concentration, participation, coping, decision-making and worthlessness. LIMITATIONS: The cross-sectional analysis needs replication. CONCLUSIONS: The GHQ-12 showed a hierarchy of distress, but IIO is only demonstrated for six of the items, and the scale could therefore be shortened. Adopting brief, hierarchical scales with IIO may be beneficial in both clinical and research contexts.

Latent class analysis of co-morbidity in the Adult Psychiatric Morbidity Survey in England 2007: implications for DSM-5 and ICD-11.

BACKGROUND: Psychiatric co-morbidity is complex and ubiquitous. Our aim was to describe the extent, nature and patterning of psychiatric co-morbidity within a representative sample of the adult population of England, using latent class analysis. METHOD: Data were used from the 2007 Adult Psychiatric Morbidity Survey, a two-phase national household survey undertaken in 2007 comprising 7325 participants aged 16 years and older living in private households in England. The presence of 15 common mental health and behavioural problems was ascertained using standardized clinical and validated self-report measures, including three anxiety disorders, depressive episode, mixed anxiety depressive disorder, psychosis, antisocial and borderline personality disorders, eating disorders, post-traumatic stress disorder, attention deficit disorder, alcohol and drug dependencies, problem gambling and attempted suicide. RESULTS: A four-class model provided the most parsimonious and informative explanation of the data. Most participants (81.6%) were assigned to a non-symptomatic or 'Unaffected' class. The remainder were classified into three qualitatively different symptomatic classes: 'Co-thymia' (12.4%), 'Highly Co-morbid' (5.0%) and 'Addictions' (1.0%). Classes differed in mean numbers of conditions and impairments in social functioning, and these dimensions were correlated. CONCLUSIONS: Our findings confirm that mental disorders typically co-occur and are concentrated in a relatively small number of individuals. Conditions associated with the highest levels of disability, mortality and cost--psychosis, suicidality and personality disorders--are often co-morbid with more common conditions. This needs to be recognized when planning services and when considering aetiology.

Plasmacytoma-associated neuronal glycoprotein, Pang, maps to mouse chromosome 6 and human chromosome 3.

A new member of the immunoglobulin/fibronectin superfamily of adhesion molecules, Pang (plasmacytoma-associated neuronal glycoprotein), was recently isolated from a plasmacytoma. In previous studies, Pang was found to be normally expressed in the brain and ectopically activated by intracisternal A-type particle long terminal repeats in plasmacytomas. In this study, Pang was initially mapped to mouse Chr 6 by somatic cell hybrid analysis and further positioned on the chromosome between Wnt7a and Pcp1. Southern blot analysis of human-rodent somatic cell hybrids together with predictions from the mouse map location indicate that human PANG is located at 3p26.

Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B (PPP3R1) are located on human chromosomes 4, 10q21-->q22 and 2p16-->p15 respectively.

Calcineurin (also called protein phosphatase-2B) is a calmodulin-regulated protein phosphatase which plays an important role in signal transduction. The enzyme is a heterodimer of a 58-59 kDa calmodulin-binding catalytic subunit (calcineurin A) and a small (i.e. 19 kDa) Ca(2+)-binding regulatory subunit (calcineurin B). The highly conserved calcineurin B is encoded by a single gene in all tissues except testes, whereas there are three isoforms of calcineurin A (alpha, beta and gamma) encoded by genes on three different chromosomes. This enzyme can play a critical role in transcriptional regulation and growth control in T lymphocytes by a mechanism believed to involve dephosphorylation of the nuclear factor NF-AT which is essential for transcription of the interleukin-2 gene. To better evaluate the potential role of the calcineurin genes in human genetic disorders, we have studied their chromosome locations. Calcineurin B (PPP3R1) is located on human chromosome 2p16-->p15 and calcineurin A beta (PPP3CB, previous gene symbol CALNB) is present on 10q21-->q22. We confirm the localization of calcineurin A alpha (PPP3CA, previous gene symbol CALNA) to chromosome 4 without regional localization.

Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene.

G alpha q is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C beta. We report the isolation and characterization of cDNA clones from a frontal cortex cDNA library encoding human G alpha q. The encoded protein is 359 amino acids long and is identical in all but one amino acid residue to mouse G alpha q. Analysis of human genomic DNA reveals an intronless sequence with strong homology to human G alpha q cDNA. In comparison to G alpha q cDNA, this genomic DNA sequence includes several small deletions and insertions that alter the reading frame, multiple single base changes, and a premature termination codon in the open reading frame, hallmarks of a processed pseudogene. Probes derived from human G alpha q cDNA sequence map to both chromosomes 2 and 9 in high-stringency genomic blot analyses of DNA from a panel of human-rodent hybrid cell lines. PCR primers that selectively amplify the pseudogene sequence generate a product only when DNA containing human chromosome 2 is used as the template, indicating that the authentic G alpha q gene (GNAQ) is located on chromosome 9. Regional localization by FISH analysis places GNAQ at 9q21 and the pseudogene at 2q14.3-q21.

Chromosomal organization and transcriptional regulation of human GEM and localization of the human and mouse GEM loci encoding an inducible Ras-like protein.

The mitogen-induced gene, GEM, encodes a GTP-binding protein that belongs to a new family within the Ras superfamily. The regulated expression pattern of Gem suggests a role for this protein in cellular responses to growth stimulation. To facilitate the assessment of the possible role of GEM in heritable and spontaneous disease processes, the genomic organization of human GEM and the chromosomal localization of human and murine GEM have been determined. GEM has been localized to the long arm of human chromosome 8 (8q13-q21) between the D8S85 and CA2 loci by genetic linkage analysis using an MspI restriction fragment length polymorphism within GEM. No consistent somatic chromosomal alterations or heritable diseases are associated with this region. Mouse Gem maps to the proximal region of chromosome 4 between Mos and Cga. To gain insight into the transcriptional regulation of GEM, we have established the transcriptional initiation site of GEM in human T cells and defined a 5' upstream region sufficient for mitogen-responsive, inducible transcription.

Restriction polymorphisms of the ceruloplasmin gene on chromosome 3.

Using a probe isolated from a human liver cDNA library, polymorphisms were observed in the human ceruloplasmin gene with the enzymes PstI and MspI. The PstI polymorphism was frequent (allele frequencies, 0.46 and 0.54) whereas the polymorphisms found with MspI were rare.

Genomic organization and chromosomal localization of the DUSP2 gene, encoding a MAP kinase phosphatase, to human 2p11.2-q11.

The mitogen-induced gene, DUSP2, encodes a nuclear protein, PAC1, that acts as a dual-specific protein phosphatase with stringent substrate specificity for MAP kinase. MAP kinase phosphorylation and consequent enzymatic activation is a central and often obligatory component in signal transduction initiated by growth factor stimulation or resulting from various types of oncogenic transformation. DUSP2 downregulates intracellular signal transduction through the dephosphorylation/inactivation of MAP kinases. To facilitate assessment of the possible role of DUSP2 in growth processes, the genomic structure and chromosomal location of the gene have been determined. DUSP2 has been localized to the pericentromeric region of human chromosome 2 (2p11.2-q11) by analysis of somatic cell hybrids, in situ chromosome hybridization, and genetic linkage analysis using a single-strand conformational polymorphism (SSCP) that has been identified in the 3' UTR of the gene. No consistent translocations or deletions at this chromosomal site have been reported in hematopoietic neoplasias or other tumors.

CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human chromosome 10 and mouse chromosome 19.

Helix-loop-helix proteins contain stretches of DNA that encode two amphipathic alpha-helices joined by a loop structure and are involved in protein dimerization and transcriptional regulation essential to a variety of cellular processes. CHUK, a newly described conserved helix-loop-helix ubiquitous kinase, was mapped by somatic cell hybrid analyses to human Chr 10q24-q25. Chuk and a related sequence, Chuk-rs1, were mapped to mouse chromosomes 19 and 16, respectively, by a combination of somatic cell hybrid, recombinant inbred, and backcross analyses.

Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1).

Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences (Tarbp2-rs1, Tarbp2-rs2). The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells.

Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.

The nuclear receptor superfamily of transcription factors, which includes the retinoic acid receptors and v-erb A, play important roles in the molecular control of hematopoiesis. To identify nuclear receptors expressed in hematopoietic cells, we screened a human bone marrow cDNA library using a degenerate oligonucleotide and isolated a 1.85-kb full-length cDNA encoding a new human member of this superfamily, the peroxisome proliferator activated receptor gamma (hPPAR gamma). Two different hPPAR gamma transcripts were expressed in hematopoietic cells: a 1.85-kb transcript, which corresponds to the full-length mRNA (PPAR gamma 1), and a 0.65-kb transcript (PPAR gamma 2), which cannot encode all of the nuclear receptor functional domains. Normal neutrophils and peripheral blood lymphocytes, as well as circulating leukemic cells from patients with AML, ALL, and CML, express only PPAR gamma 2 on Northern blot analysis. In contrast, only the PPAR gamma 1 transcript was detected in a variety of human leukemia cell lines and in cultured normal primary bone marrow stromal cells. Both transcripts were detected in various fetal and adult nonhematopoietic tissues. We mapped the location of the hPPAR gamma gene to human chromosome 3p25 by somatic cell hybridization and linkage analysis. PPARs have been shown to be activated by peroxisome proliferating agents, long-chain fatty acids and arachidonic acid. Human PPAR gamma, although homologous to the PPAR gamma s of other species, has unique sequence and amino acid differences. Identification of hPPAR gamma will allow further understanding of its role in human cellular leukotriene, prostaglandin, and peroxide degradative or synthetic pathways, as well as its role in lipid metabolism and regulation of adipocyte differentiation.