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A paradox of genetic and environmental factors are linked to schizophrenia. For example, cases may be familial or spontaneous. Extensive studies have failed to identify a single gene or small group of genes that accounts for the majority of cases. The complex inheritance pattern suggests a strong environmental component even for those who are predisposed to disease. Environmental factors linked to disease occur early in development. Our goal is to identify common biochemical pathways affected by factors linked to schizophrenia.
Our studies included DNA comparisons between monozygotic twins discordant for schizophrenia, computational evaluations of genomic positions of candidate genes using Genbank resources, and molecular genetic/epigenetic studies on dopamine metabolism in the synaptic cleft.
Twins studies linked schizophrenia to somatic DNA instability (p = <0.01). Genomic studies linked schizophrenia to interspersed fragile site regions (p = 0.001) of the genome that are hot spots for mutation and epigenetics changes. The molecular studies on dopamine metabolism linked schizophrenia to aberrant genetic and epigenetic changes.
These, and other results, point to the confluence of DNA stability (i.e. DNA replication/repair) and epigenetic modification. DNA replication/repair and epigenetic modification are linked at both the macromolecular and biochemical level, require folate, methionine, and cobalamine, and compete for intermediates important for the cellular response to oxidative stress. Mutations in these pathways are linked to schizophrenia, as have deficits in the essential nutrients. The consequences of genetic and/or environmental perturbations to these pathways are complex because many essential pathways and processes are affected.
Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD.
We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts.
We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47–2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69–2.84), MS (IRR 1.79; 95%CI: 1.29–2.50) and RA (IRR 1.61; 95%CI: 1.29–1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45–64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls.
IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.
We explore whether simple behavioural insights techniques can be successful for addressing a policy issue within one of society's more complex and difficult sectors: child protection. Child protection reporting practices in New South Wales, Australia, reveal that the public's primary response is to report to the statutory authority, who only deal with cases of the highest risk. As a result, a large volume of statutory resources are spent processing lower-risk reports that lead to no benefits for lower-risk families and slow down response times for families that require a statutory response most. Our goal was to reduce lower-risk reporting by encouraging alternative responses to these situations. To do this, we altered report feedback for cases deemed lower risk in order to make alternative responses more salient and we added a persuasive message framed as a gain or loss. We then examined subsequent reporting accuracy. We found that our trial was linked to a modest improvement in reporting accuracy, though the results may have been diluted by a spill-over effect. We discuss how facilitating a greater behavioural change likely requires multi-organization collaborations, extending the range of insights drawn from behavioural science and/or addressing issues from multiple angles.
After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.
Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.
We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40).
The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Annual radiocarbon from a massive Porites lutea coral collected from Hon Tre Island, Vietnam, South China Sea (SCS) was analyzed over a ~100-yr-long period from AD 1900 to 1986. The pre-bomb results from 1900–1953 show a steady Δ14C value of –54.4±1.8‰ (n=60). These values are similar to coral records located in the central and southern SCS and from Indonesian waters, but are lower than those from Japan. Following the input of anthropogenic bomb 14C, our results show a sharp increase in Δ14C from 1960, reaching a peak value of 155.3‰ in 1973. The Hon Tre Island post-bomb Δ14C values are lower than those of other corals located in the SCS and Japan, but higher compared to those in the Indonesian Seas. This study infers a seasonal input of upwelled water depleted in 14C from the deeper SCS basin that originates from the tropical Pacific via the Luzon Strait. The bifurcation of the North Equatorial Current feeds the surface and intermediate currents in the SCS and Makassar Strait region. However, unlike the Makassar site, this study’s coral Δ14C does not receive lower 14C water from the South Pacific Equatorial Current. The Vietnam record therefore represents a unique oceanographic position, reflecting the seasonal influence of older, deeper SCS waters that upwell periodically in this area and have modified the surface waters locally in this region over the last 100 yr.
This study investigated local perceptions of changes stemming from a long-standing Group Interpersonal Psychotherapy (IPT-G) program for the treatment of depression in rural Uganda. The study was conducted in a low-income, severely HIV/AIDS-affected area where in 2001 the prevalence of depression was estimated at 21% among adults.
Data were collected using free-listing and key informant qualitative interviews. A convenience sample of 60 free-list respondents was selected from among IPT-G participants, their families, and other community members from 10 Ugandan villages. Twenty-two key informants and six IPT-G facilitators were also interviewed.
Content analysis yielded five primary categories of change in the community related to the IPT-G program: (1) improved school attendance for children; (2) improved productivity; (3) improved sanitation in communities; (4) greater cohesion among community members; and (5) reduced conflict in families. Community members and IPT-G facilitators suggested that as depression remitted, IPT-G participants became more hopeful, motivated and productive.
Results suggest that providing treatment for depression in communities with high depression prevalence rates may lead to positive changes in a range of non-mental health outcomes.
Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.
The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0–16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans.
TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity.
The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
The association between physical disorders and suicide remains unclear. The aim of this study was to examine the relationship between physical disorders and suicide after accounting for the effects of mental disorders.
Individuals who died by suicide (n = 2100) between 1996 and 2009 were matched 3:1 by balancing score to general population controls (n = 6300). Multivariate conditional logistic regression compared the two groups across physician-diagnosed physical disorders [asthma, chronic obstructive pulmonary disease (COPD), ischemic heart disease, hypertension, diabetes, cancer, multiple sclerosis and inflammatory bowel disease], adjusting for mental disorders and co-morbidity. Secondary analyses examined the risk of suicide according to time since first diagnosis of each physical disorder (1–90, 91–364, ⩾ 365 days). Similar analyses also compared individuals with suicide attempts (n = 8641) to matched controls (n = 25 923).
Cancer was associated with increased risk of suicide [adjusted odds ratio (AOR) 1.40, 95% confidence interval (CI) 1.03–1.91, p < 0.05] even after adjusting for all mental disorders. The risk of suicide with cancer was particularly high in the first 90 days after initial diagnosis (AOR 4.10, 95% CI 1.71–9.82, p < 0.01) and decreased to non-significance after 1 year. Women with respiratory diseases had elevated risk of suicide whereas men did not. COPD, hypertension and diabetes were each associated with increased odds of suicide attempts in adjusted models (AORs ranged from 1.20 to 1.73).
People diagnosed with cancer are at increased risk of suicide, especially in the 3 months following initial diagnosis. Increased support and psychiatric involvement should be considered for the first year after cancer diagnosis.
FFQ are popular instruments for assessing dietary intakes in epidemiological studies but have not been validated for use in severely obese pregnancy. The aim of the present study was to compare nutrient intakes assessed by an FFQ with those obtained from a food diary among severely obese pregnant women.
Comparison of an FFQ containing 170 food items and a food diary for 4 d (three weekdays and one weekend day); absolute agreement was assessed using the paired t test and relative agreement by Pearson/Spearman correlation, cross-classification into tertiles and weighted kappa values.
Antenatal metabolic clinic for severely obese women.
Thirty-one severely obese (BMI at booking ≥40·0 kg/m2) and thirty-two lean control (BMI = 20·0–24·9 kg/m2) pregnant women.
The findings showed that nutrient intakes estimated by the FFQ were significantly higher than those from the food diary; average correlation was 0·32 in obese and 0·43 in lean women. A mean of 48·5 % of obese and 47·3 % of lean women were correctly classified, while 12·9 % (obese) and 10·0 % (lean) were grossly misclassified. Weighted κ values ranged from −0·04 to 0·79 in obese women and from 0·16 to 0·78 in lean women.
Overall, the relative agreement between the FFQ and food diary was lower in the obese group than in the lean group, but was comparable with earlier studies conducted in pregnant women. The validity assessments suggest that the FFQ is a useful tool for ranking severely obese pregnant women according to the levels of their dietary intake.
SLACS for the masses is the extension of the successful Sloan Lens ACS (SLACS) survey (Bolton et al. 2006, Treu et al. 2006, Koopmans et al. 2006, Gavazzi et al. 2007 and Bolton et al. 2008) but focuses on the lower-mass end of elliptical galaxies (EGs) to yield a more complete strong-lens sample. As to date, 118 out of the 137 proposed candidates have been observed and inspected individually.
The Working Group on Mental Health and Psychosocial Support was convened as part of the 2009 Harvard Humanitarian Action Summit. The Working Group chose to focus on ethical issues in mental health and psychosocial research and programming in humanitarian settings. The Working Group built on previous work and recommendations, such as the Inter-Agency Standing Committee's Guidelines on Mental Health and Psychosocial Support in Emergency Settings.
The objective of this working group was to address one of the factors contributing to the deficiency of research and the need to develop the evidence base on mental health and psychosocial support interventions during complex emergencies by proposing ethical research guidelines. Outcomes research is vital for effective program development in emergency settings, but to date, no comprehensive ethical guidelines exist for guiding such research efforts.
Working Group members conducted literature reviews which included peer-reviewed publications, agency reports, and relevant guidelines on the following topics: general ethical principles in research, cross-cultural issues, research in resource-poor countries, and specific populations such as trauma and torture survivors, refugees, minorities, children and youth, and the mentally ill. Working Group members also shared key points regarding ethical issues encountered in their own research and fieldwork.
The group adapted a broad definition of the term “research”, which encompasses needs assessments and data gathering, as well as monitoring and evaluation. The guidelines are conceptualized as applying to formal and informal processes of assessment and evaluation in which researchers as well as most service providers engage. The group reached consensus that it would be unethical not to conduct research and evaluate outcomes of mental health and psychosocial interventions in emergency settings, given that there currently is very little good evidence base for such interventions. Overarching themes and issues generated by the group for further study and articulation included: purpose and benefits of research, issues of validity, neutrality, risk, subject selection and participation, confidentiality, consent, and dissemination of results.
The group outlined several key topics and recommendations that address ethical issues in conducting mental health and psychosocial research in humanitarian settings. The group views this set of recommendations as a living document to be further developed and refined based on input from colleagues representing different regions of the globe with an emphasis on input from colleagues from low-resource countries.
DNA restriction endonuclease (Hae III and Hind III) total digest and 16S and 23S ribosomal (r)RNA gene patterns (ribopatterns) were determined for 18 isolates of Campylobacter jejuni from three separate outbreaks of diarrhoea in the north of England. Strains were also characterized by biotyping, serotyping and phage typing. Comparisons of the DNA patterns by visual and numerical methods revealed five distinct strain groupings with clear differences between isolates from different outbreaks as well as some heterogeneity between strains within the community outbreak and one of the school outbreaks. An excellent correlation was observed between the genomic DNA fingerprints data and the Preston bacteriophage group, both of which gave better discrimination than biotyping and serotyping alone or in combination. Only one phage group (PG 37) was not confirmed by the DNA data. DNA fingerprints therefore provide additional information of value in studying the epidemiology of outbreaks of C. jejuni.
The General Insurance Premium Rating Issues Working Party (GRIP) was established by the General Insurance Board of the Faculty and Institute of Actuaries in 2005 to review actuarial involvement in premium rating issues, pricing being one of the key areas in which actuaries work.
GRIP published a full report in January 2007, which is available at www.actuaries.org.uk/grip. This short paper summarises the recommendations of that full report. Further background, discussion and the rationale for these recommendations are set out in more detail in the full report.
A population-based case–control study of diet, inherited susceptibility and prostate cancer was undertaken in the lowlands and central belt of Scotland to investigate the effect of phyto-oestrogen intake and serum concentrations on prostate cancer risk. A total of 433 cases and 483 controls aged 50–74 years were asked to complete a validated FFQ and provide a non-fasting blood sample. Multivariate logistic regression analysis found significant inverse associations with increased serum concentrations of enterolactone (adjusted OR 0·40, 95 % CI 0·22, 0·71] and with the consumption of soy foods (adjusted OR 0·52, 95 % CI 0·30, 0·91). However, no significant associations were observed for isoflavone intake or serum genistein, daidzein and equol. This study supports the hypotheses that soy foods and enterolactone metabolised from dietary lignans protect against prostate cancer in older Scottish men.
Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS.
Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range <25 to >130) using age-appropriate tests of intelligence.
On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z=−2·49, p=0·01) and total CT count (Spearman's ρ=−0·30, p=0·04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=−2·43, p=0·02) and temporal (regression coefficient=−1·60, p=0·02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0·05 and p=0·06 respectively) with ID.
The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence.
Escherichia coli O157 causes a range of illnesses from mild diarrhoea to haemolytic uraemic syndrome (HUS) which carries a mortality rate of 3·7%. Infection is more common in the under-5s. Between 1995 and 2000, 106 outbreaks of E. coli O157 were reported in England and Wales. Recreational water is well documented as a transmission route for infectious diseases worldwide. In the United Kingdom there have been very few reported outbreaks associated with swimming pools due to the relative susceptibility of E. coli O157 to adequate levels of free chlorine. This report describes the investigation of an outbreak associated with a local leisure centre pool and makes recommendations about the safe management of such facilities.
Specimens of human faeces were tested by a rapid strategy for detection of Campylobacter jejuni lineages by the presence of specific single nucleotide polymorphisms (SNPs) based on the C. jejuni multi locus sequence typing (MLST) scheme. This strategy was derived from analysis of the MLST databases to identify clonal complex specific SNPs followed by the design of real-time PCR assays to enable identification of six major C. jejuni clonal complexes associated with cases of human infection. The objective was to use the MLST SNP-based assays for the direct detection of C. jejuni by clonal complex from specimens of human faeces, and then confirm the accuracy of the clonal complex designation from the SNP-based assays by performing MLST on the cultured faecal material, this targeted at determining the validity of direct molecular specimen identification. Results showed it was possible to identify 38% of the isolates to one of the six major MLST clonal complexes using a rapid DNA extraction method directly from faeces in under 3 h. This method provides a novel strategy for the use of real-time PCR for detection and characterization beyond species level, supplying real-time epidemiological data, which is comparable with MLST results.