Social fragmentation, deprivation and urbanicity: relation to first-admission rates for psychoses

<i>Declaration</i> <i>of</i> <i>interest</i>: None. <i>Background</i>: Social disorganisation, fragmentation and isolation have long been posited as influencing the rate of psychoses at area level. Measuring such societal constructsis difficult. A census-based index measuring social fragmentation has been proposed. <i>Aims</i>: To investigate the association between first-admission rates for psychosis and area-based measures of social fragmentation, deprivation and urban/rural index. <i>Method</i>: We used indirect standardisation methods and logistic regression models to examine associations of social fragmentation, deprivation and urban/rural categories with first admissions for psychoses in Scotland for the 5-year period 1989–1993. <i>Results</i>: Areas characterised by high social fragmentation had higher first-ever admission rates for psychosis independent of deprivation and urban/rural status. There was a dose–response relationship between social fragmentation category and first-ever admission rates for psychosis. There was no statistically significant interaction between social fragmentation, deprivation and urban/rural index. <i>Conclusions</i>: First-admission rates are strongly associated with measures of social fragmentation, independent of material deprivation and urban/rural category

Community Perspectives on the Impact of Climate Change on Health in Nunavut, Canada

The purpose of this study was to explore community perspectives on the most important ways that climate change is affecting the health of northern peoples. The study was conducted in Iqaluit, Nunavut, using a participatory action approach and the photovoice research method. Participants identified themes and patterns in the data and developed a visual model of the relationships between the themes identified. Five themes emerged from the data: the direct impacts of climate change on the health of individuals and communities, the transition from past climates to future climates, necessary adaptation to the changing climate in the North, the call to action (individual, regional, and national), and reflection on the past and changing knowledge systems. A climate change and health model was developed to illustrate the relationships between the themes. Participants in this study conceptualized health and climate change broadly. Participants believed that by engaging in a process of ongoing reflection, and by continually incorporating new knowledge and experiences into traditional knowledge systems, communities may be better able to adapt and cope with the challenges to health posed by climate change.L’objectif de cette étude consistait à explorer diverses perspectives communautaires quant aux manières les plus importantes dont le changement climatique a des incidences sur la santé des gens du Nord. L’étude a été réalisée à Iqaluit, au Nunavut, au moyen d’une méthode d’action et de recherche participative faisant appel à la « photovoice ». Les participants ont déterminé les thèmes de même que les tendances caractérisant les données, puis ont abouti à un modèle visuel pour établir des relations entre les thèmes ainsi déterminés. Les données ont donné lieu à la formulation de cinq thèmes, soit les incidences directes du changement climatique sur la santé des gens et des collectivités; la transition des anciens climats aux nouveaux climats; l’adaptation nécessaire au climat changeant dans le Nord; un appel à l’action (individuel, régional et national); et une réflexion sur les systèmes de savoir du passé qui sont en pleine évolution. Ensuite, un modèle de changement climatique et de santé a été élaboré dans le but d’illustrer les liens existant entre les divers thèmes. Les participants à cette étude ont conceptualisé le changement climatique et ses incidences sur la santé à grande échelle. Ils croyaient qu’en s’adonnant à un processus de réflexion continue et qu’en intégrant constamment de nouvelles connaissances et expériences aux systèmes de savoir traditionnel, les collectivités pourraient être mieux placées pour s’adapter et relever les défis posés par le changement climatique en matière de santé

Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia

Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants’ mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4). Current cognitive ability was associated with genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia

Ecological association between a deprivation index and mortality in France over the period 1997 – 2001: variations with spatial scale, degree of urbanicity, age, gender and cause of death

<p>Abstract</p> <p>Background</p> <p>Spatial health inequalities have often been analysed in terms of deprivation. The aim of this study was to create an ecological deprivation index and evaluate its association with mortality over the entire mainland France territory. More specifically, the variations with the degree of urbanicity, spatial scale, age, gender and cause of death, which influence the association between mortality and deprivation, have been described.</p> <p>Methods</p> <p>The deprivation index, 'FDep99', was developed at the '<it>commune</it>'(smallest administrative unit in France) level as the first component of a principal component analysis of four socioeconomic variables.</p> <p>Proxies of the Carstairs and Townsend indices were calculated for comparison.</p> <p>The spatial association between FDep99 and mortality was studied using five different spatial scales, and by degree of urbanicity (five urban unit categories), age, gender and cause of death, over the period 1997–2001.</p> <p>'Avoidable' causes of death were also considered for subjects aged less than 65 years. They were defined as causes related to risk behaviour and primary prevention (alcohol, smoking, accidents).</p> <p>Results</p> <p>The association between the FDep99 index and mortality was positive and quasi-log-linear, for all geographic scales. The standardized mortality ratio (SMR) was 24% higher for the <it>communes </it>of the most deprived quintile than for those of the least deprived quintile. The between-urban unit category and between-<it>région </it>heterogeneities of the log-linear associations were not statistically significant. The association was positive for all the categories studied and was significantly greater for subjects aged less than 65 years, for men, and for 'avoidable' mortality.</p> <p>The amplitude and regularity of the associations between mortality and the Townsend and Carstairs indices were lower.</p> <p>Conclusion</p> <p>The deprivation index proposed reflects a major part of spatial socioeconomic heterogeneity, in a homogeneous manner over the whole country. The index may be routinely used by healthcare authorities to observe, analyse, and manage spatial health inequalities.</p

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

Hypoxia Sensitive Metal β-Ketoiminate Complexes Showing Induced Single Strand DNA Breaks and Cancer Cell Death by Apoptosis

A series of ruthenium and iridium complexes have been synthesised and characterised with 20 novel crystal structures discussed. The library of β-ketoiminate complexes has been shown to be active against MCF-7 (human breast carcino-ma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma) and A2780cis (cisplatin resistant human ovarian carcinoma) cell lines, with selected complexes being more than three times as active as cisplatin against the A2780cis cell line. Complexes have also been shown to be highly active under hypoxic conditions, with the activities of some complexes increasing with a decrease in O2 concentration. The enzyme thioredoxin reductase is over-expressed in cancer cells and complexes reported herein have the advantage of inhibiting this enzyme, with IC50 values measured in the nanomolar range. The anti-cancer activity of these complexes was further investigated to determine whether activity is due to effects on cellular growth or cell survival. The complexes were found to induce significant cancer cell death by apoptosis with levels induced correlating closely with activity in chemosensitivity studies. As a possible cause of cell death, the ability of the complexes to induce damage to cellular DNA was also assessed. The complexes failed to induce double strand DNA break or DNA crosslinking but induced significant levels of single DNA strand breaks indi-cating a different mechanism of action to cisplatin