Bamboozled! Resolving deep evolutionary nodes within the phylogeny of bamboo corals (Octocorallia: Scleralcyonacea: Keratoisididae).

Keratoisididae is a globally distributed, and exclusively deep-sea, family of octocorals that contains species and genera that are polyphyletic. An alphanumeric system, based on a three-gene-region phylogeny, is widely used to describe the biodiversity within this family. That phylogeny identified 12 major groups although it did not have enough signal to explore the relationships among groups. Using increased phylogenomic resolution generated from Ultraconserved Elements and exons (i.e. conserved elements), we aim to resolve deeper nodes within the family and investigate the relationships among those predefined groups. In total, 109 libraries of conserved elements were generated from individuals representing both the genetic and morphological diversity of our keratoisidids. In addition, the conserved element data of 12 individuals from previous studies were included. Our taxon sampling included 11 of the 12 keratoisidid groups. We present two phylogenies, constructed from a 75% (231 loci) and 50% (1729 loci) taxon occupancy matrix respectively, using both Maximum Likelihood and Multiple Species Coalescence methods. These trees were congruent at deep nodes. As expected, S1 keratoisidids were recovered as a well-supported sister clade to the rest of the bamboo corals. S1 corals do not share the same mitochondrial gene arrangement found in other members of Keratoisididae. All other bamboo corals were recovered within two major clades. Clade I comprises individuals assigned to alphanumeric groups B1, C1, D1&D2, F1, H1, I4, and J3 while Clade II contains representatives from A1, I1, and M1. By combining genomics with already published morphological data, we provide evidence that group H1 is not monophyletic, and that the division between other groups - D1 and D2, and A1 and M1 - needs to be reconsidered. Overall, there is a lack of robust morphological markers within Keratoisididae, but subtle characters such as sclerite microstructure and ornamentation seem to be shared within groups and warrant further investigation as taxonomically diagnostic characters.

Design of an individualised questionnaire to measure the impact of cancer on quality of life: The cancer dependent quality of life (CancerDQoL) questionnaire.

AIM: To design an individualised questionnaire to measure the impact of cancer and its treatments on quality of life (QoL). MATERIALS & METHODS: Design of the Cancer-Dependent Quality of Life (CancerDQoL) questionnaire was based on the Audit of Diabetes Dependent QoL (ADDQoL) questionnaire and related -DQoLs for other conditions. Item selection, face validity and content validity were established through clinician and patient ratings of the importance and relevance of 60 domains from the -DQoL Item Library, and semi-structured interviews with 25 English-speaking participants with a range of cancers attending a cancer centre in Zimbabwe (age range: 25-78 years; 16 women, 9 men). Ten interviews were subsequently conducted with UK English-speaking participants with a range of cancers attending Maggie's Centres in London and Dundee (age range: 40-76; 5 women, 5 men) to adapt the CancerDQoL for UK use. RESULTS: The first draft of the CancerDQoL contained 25 domain-specific items from the -DQoL Item Library plus four overview items. Zimbabwean participants indicated that cancer negatively impacted on all life domains included, except 'having children'. Weighted impact (impact ratings multiplied by importance) was most negative for 'sex life', 'depend on others' and 'physical capability'. The least negative weighted impact was found for 'having children', 'spiritual/religious life' and 'past medical/self-care'. UK interviews confirmed no new items were required. CONCLUSIONS: Face and content validity of the CancerDQoL is established for an adult sample of English-speaking cancer patients in Zimbabwe and confirmed in an adaptation following UK interviews.

Testicular Adrenal Rest Tumors or Bilateral Leydig Cell Tumors?

Testicular Adrenal Rest Tumors, also known as Testicular Tumors of the Androgenital Syndrome, are benign tumors found in the testes of patients with congenital adrenal hyperplasia. While considered benign, they are significant in that they can proliferate within the rete testis and cause infertility. We present a patient who appeared to have findings consistent with testicular adrenal rest tumors and is in the process of malignancy rule out.

Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes.

INTRODUCTION: FTND (FagerstrÓ§m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. METHODS: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. RESULTS: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. CONCLUSIONS: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. IMPLICATIONS: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

Gender Differences in HIV Testing, Diagnosis, and Linkage to Care in Healthcare Settings: Identifying African American Women with HIV in Chicago.

Women account for 25% of all people living with HIV and 19% of new diagnoses in the United States. African American (AA) women are disproportionately affected. Yet, differences in the care continuum entry are not well understood between patient populations and healthcare sites. We aim to examine gender differences in diagnosis and linkage to care (LTC) in the Expanded HIV Testing and Linkage to Care (X-TLC) program within healthcare settings. Data were collected from 14 sites on the South and West sides of Chicago. Multivariate logistic regression analysis was used to determine the differences in HIV diagnoses and LTC by gender and HIV status. From 2011 to 2016, X-TLC performed 281,017 HIV tests; 63.7% of those tested were women. Overall HIV seroprevalence was 0.57%, and nearly one third (29.4%) of HIV-positive patients identified were cisgender women. Of newly diagnosed HIV-positive women, 89% were AA. 58.5% of new diagnoses in women were made at acute care hospitals, with the remainder at community health centers. Women who were newly diagnosed had a higher baseline CD4 count at diagnosis compared with men. Overall, women had lower odds of LTC compared with men (adjusted odds ratio = 0.58, 95% confidence interval 0.44-0.78) when controlling for patient demographics and newly versus previously diagnosed HIV status. Thus, interventions that focus on optimizing entry into the care continuum for AA women need to be explored.

Genome-wide association meta-analysis of age at first cannabis use.

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Background: Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal. Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness. Results: Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ≤ 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ≤ 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = -0.004, 95% CI -0.023 to 0.016, P=0.708, I2 = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively. Conclusions: Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research.

Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: findings from a UK birth cohort.

BACKGROUND: Evidence on the role of cannabis as a gateway drug is inconsistent. We characterise patterns of cannabis use among UK teenagers aged 13-18 years, and assess their influence on problematic substance use at age 21 years. METHODS: We used longitudinal latent class analysis to derive trajectories of cannabis use from self-report measures in a UK birth cohort. We investigated (1) factors associated with latent class membership and (2) whether latent class membership predicted subsequent nicotine dependence, harmful alcohol use and recent use of other illicit drugs at age 21 years. RESULTS: 5315 adolescents had three or more measures of cannabis use from age 13 to 18 years. Cannabis use patterns were captured as four latent classes corresponding to 'non-users' (80.1%), 'late-onset occasional' (14.2%), 'early-onset occasional' (2.3%) and 'regular' users (3.4%). Sex, mother's substance use, and child's tobacco use, alcohol consumption and conduct problems were strongly associated with cannabis use. At age 21 years, compared with the non-user class, late-onset occasional, early-onset occasional and regular cannabis user classes had higher odds of nicotine dependence (OR=3.5, 95% CI 0.7 to 17.9; OR=12.1, 95% CI 1.0 to 150.3; and OR=37.2, 95% CI 9.5 to 144.8, respectively); harmful alcohol consumption (OR=2.6, 95% CI 1.5 to 4.3; OR=5.0, 95% CI 2.1 to 12.1; and OR=2.6, 95% CI 1.0 to 7.1, respectively); and other illicit drug use (OR=22.7, 95% CI 11.3 to 45.7; OR=15.9, 95% CI 3.9 to 64.4; and OR=47.9, 95% CI 47.9 to 337.0, respectively). CONCLUSIONS: One-fifth of the adolescents in our sample followed a pattern of occasional or regular cannabis use, and these young people were more likely to progress to harmful substance use behaviours in early adulthood.

Body mass index, body dissatisfaction and adolescent smoking initiation.

BACKGROUND: Smoking influences body weight, but there is little evidence as to whether body mass index (BMI) and body dissatisfaction increase smoking initiation in adolescents. METHODS: We evaluated the association between measured BMI, body dissatisfaction and latent classes of smoking initiation (never smokers, experimenters, late onset regular smokers, early onset regular smokers) in the Avon Longitudinal Study of Parents and Children. In observational analyses we used BMI (N=3754) and body dissatisfaction at age 10.5 years (N=3349). In Mendelian randomisation (MR) analysis, we used a BMI genetic risk score of 76 single nucleotide polymorphisms (N=4017). RESULTS: In females, higher BMI was associated with increased odds of early onset regular smoking (OR: 1.11, 95% CI: 1.04, 1.18) compared to being a never smoker, but not clearly associated with experimenting with smoking (OR: 1.04, 95% CI: 0.99, 1.10) or late onset regular smoking (OR: 1.01, 95% CI: 0.94, 1.09). No clear evidence was found for associations between BMI and smoking initiation classes in males (p-value for sex interaction≤0.001). Body dissatisfaction was associated with increased odds of late-onset regular smoking (OR: 1.71, 95% CI: 1.32, 1.99) in males and females combined (P-value for sex interaction=0.32). There was no clear evidence for an association between the BMI genetic risk score and smoking latent classes in males or females but estimates were imprecise. CONCLUSIONS: BMI in females and body dissatisfaction in males and females are associated with increased odds of smoking initiation, highlighting these as potentially important factors for consideration in smoking prevention strategies.

Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users.

INTRODUCTION: Biological tests of drug use can be used to inform clinical and legal decisions and hold potential to provide evidence for epidemiological studies where self-reported behaviour may be unavailable or unreliable. We test whether hair can be considered as a reliable marker of cannabis exposure. METHODS: Hair samples were collected from 136 subjects who were self-reported heavy, light or non-users of cannabis and tested using GC-MS/MS. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for five cannabinoids (tetrahydrocannabinol [THC], THC-OH, THC-COOH, cannabinol and cannabidiol). Samples also were segmented in 1 cm sections representing 1 month exposure and the correlation between amount of cannabinoid detected and self-reported cannabis consumption tested. RESULTS: All five cannabinoids were detected. Seventy-seven percent of heavy users, 39% of light users and 0% of non-users tested positive for THC. The sensitivity of detection of THC was 0.77 (0.56-0.91) comparing heavy cannabis smokers with light and non-users, whereas the sensitivity of other cannabinoids generally was considerably lower. The positive and negative predictive value of detection of THC were 0.57 (0.39-0.74) and 0.91 (0.82-0.97), respectively. A correlation of 0.52 (P < 0.001) was observed between self-reported monthly cannabis use and THC. DISCUSSION: Hair analysis can be used as a qualitative indicator of heavy (daily or near daily) cannabis consumption within the past 3 months. However, this approach is unable to reliably detect light cannabis consumption or determine the quantity of cannabis used by the individual. [Taylor M, Lees R, Henderson G, Lingford-Hughes A, Macleod J, Sullivan J, Hickman M. Comparison of cannabinoids in hair with self-reported cannabis consumption in heavy, light and non-cannabis users. Drug Alcohol Rev 2017;36:220-226].

Management of Thrombotic Microangiopathic Hemolytic Anemias with Therapeutic Plasma Exchange: When It Works and When It Does Not.

Thrombotic microangiopathies are a heterogeneous group of inherited and acquired disorders sharing a common clinical presentation of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. These disorders have been treated with plasma exchange (TPE) based on randomized controlled trials, which found this therapy to be effective in thrombotic thrombocytopenic purpura (TTP). For the remaining disorders, low- to very low-quality evidence exists for the use of TPE. When TPE is applied, the treatment regimen used for TTP is usually applied. There is a need for further evaluation of the role of TPE in the treatment of thrombotic microangiopathies other than TTP.

Evolutionary dynamics of a common sub-Antarctic octocoral family.

Sequence data were obtained for five different loci, both mitochondrial (cox1, mtMutS, 16S) and nuclear (18S, 28S rDNA), from 64 species representing 25 genera of the common deep-sea octocoral family Primnoidae. We tested the hypothesis that Primnoidae have an Antarctic origin, as this is where they currently have high species richness, using Maximum likelihood and Bayesian inference methods of phylogenetic analysis. Using a time-calibrated molecular phylogeny we also investigated the time of species radiation in sub-Antarctic Primnoidae. Our relatively wide taxon sampling and phylogenetic analysis supported Primnoidae as a monophyletic family. The base of the well-supported phylogeny was Pacific in origin, indicating Primnoidae sub-Antarctic diversity is a secondary species radiation. There is also evidence for a subsequent range extension of sub-Antarctic lineages into deep-water areas of the Indian and Pacific Oceans. Conservative and speculative fossil-calibration analyses resulted in two differing estimations of sub-Antarctic species divergence times. Conservative analysis suggested a sub-Antarctic species radiation occurred ∼52MYA (95% HPD: 36-73MYA), potentially before the opening of the Drake Passage and Antarctic Circumpolar Current (ACC) formation (41-37MYA). Speculative analysis pushed this radiation back into the late Jurassic, 157MYA (95% HPD: 118-204MYA). Genus-level groupings were broadly supported in this analysis with some notable polyphyletic exceptions: Callogorgia, Fanellia, Primnoella, Plumarella, Thouarella. Molecular and morphological evidence supports the placement of Tauroprimnoa austasensis within Dasystenella and Fannyella kuekenthali within Metafannyella.

The effect of SV 293, a D2 dopamine receptor-selective antagonist, on D2 receptor-mediated GIRK channel activation and adenylyl cyclase inhibition.

SV 293 [1-([5-methoxy-1H-indol-3-yl]methyl)-4-(4-[methylthio]​phenyl)piperidin-4-ol] binds with 100-fold higher affinity to human D2 receptors compared to the human D3 and D4 dopamine receptor subtypes. We investigated the intrinsic efficacy of this compound at the D2 dopamine receptor subtype using both: (1) a forskolin-dependent adenylyl cyclase inhibition assay and (2) an electrophysiological assay for evaluating coupling to G-protein-coupled inwardly rectifying potassium channels. In both assays SV 293 was found to be a neutral antagonist capable of blocking the effects of the full D2-like receptor agonist quinpirole. Based upon these results we propose that SV 293 is a useful pharmacological tool that can be used for both in vitro and in vivo studies to investigate the role of D2-like dopamine receptor subtypes in neurological, neuropsychiatric and movement disorders where dopaminergic pathways have been implicated.

Myeloproliferative neoplasms: diagnosis, management and treatment.

This article provides an overview of myeloproliferative neoplasms for nurses who do not specialise in haematology. Diagnosis, management and treatment of patients with these conditions is discussed, as well as long-term nursing implications.

Influence of 1,25-dihydroxy vitamin D3 on TLR4-induced activation of antigen presenting cells is dependent on the order of receptor engagement.

The vitamin D metabolite, 1,25-(OH)2D3, binds the vitamin D receptor (VDR) to exert its regulatory effects at the transcription level. VDR is expressed in professional antigen-presenting cells (pAPCs), such as macrophages (Mø) and dendritic cells (DCs). We show for the first time that the 24-hydroxylase enzyme is activated in bone marrow-derived dendritic cell (BMDC), due to 1,25(OH)2D3 stimulation which resulted in the induction of its gene, CYP24A1. Furthermore, we provide evidence that the influence of 1,25-(OH)2D3 on TLR-4-L-induced activation of pAPC is dependent on the order of VDR and TLR-4 engagement. Thus, pre-treatment of pAPC with 1,25-(OH)2D3 partially inhibited LPS-induced nitric oxide (NO) production. However, these inhibitory effects were not observed when LPS and 1,25-(OH)2D3 were added simultaneously or when LPS preceded 1,25-(OH)2D3. Moreover, we found that 1,25-(OH)2D3 pre-treatment of pAPCs did not cause general suppression since it interfered with NO levels but not with the cytokines IL-6 or TNF-α. Consequently, engagement of VDR by 1,25-(OH)2D3 can partially interfere with TLR-4-L-induced activation of pAPCs only when it occurs before TLR-4 stimulation.

Synthesis and pharmacological evaluation of fluorine-containing D3 dopamine receptor ligands.

A series of fluorine-containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized, and their affinities for human dopamine D(2), D(3), and D(4) receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e, and 21e, which bind with high affinity at D(3) (K(i) = 0.17-5 nM) and moderate to high selectivity for D(3) vs D(2) receptors (ranging from ∼25- to 163-fold). These compounds were also evaluated for intrinsic activity at D(2) and D(3) receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D(2) vs D(3) receptors. These compounds may be useful for behavioral pharmacology studies on the role of D(2)-like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D(3) receptor (K(i) = 0.17 nM for D(3), 163-fold selectivity for D(3) vs D(2) receptors), represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D(3) receptor expression.

Five Factor Model personality traits and all-cause mortality in the Edinburgh Artery Study cohort.

OBJECTIVE: To examine whether personality traits are related to all-cause mortality in a general adult population in Scotland. METHODS: The Edinburgh Artery Study began in 1987 to 1988 by recruiting 1592 men and women aged 55 to 74 years to be followed-up for atherosclerotic diseases. The NEO Five-Factor Inventory (NEO-FFI) was completed by 1035 surviving participants in 1995 to 1996. Deaths from all causes were examined in relation to personality traits and social and physical risk factors for mortality. RESULTS: During follow-up, 242 (37.1%) men and 165 (24.6%) women died. For the whole sample, there was a 28% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI openness (95% CI, 0.61-0.84) and a 18% lower rate of all-cause mortality for each 1 SD increase in NEO-FFI conscientiousness (95% CI, 0.70-0.97). In men, the risk of all-cause mortality was 0.63 (95% CI, 0.5-10.78) for a 1 SD increase in openness and 0.75 (95% CI, 0.61-0.91) for a 1 SD increase in conscientiousness. In women, none of the personality domains were significantly associated with all-cause mortality. Well fitting structural equation models in men (n = 652) showed that the relationships between conscientiousness and openness and all-cause mortality were not substantially explained by smoking, or other variables in the models. CONCLUSION: High conscientiousness and openness may be protective against all-cause mortality in men. Further investigations are needed on the mechanisms of these associations, and the influence of personality traits on specific causes of death.

An observational study of surgery-related activities between nurses and surgeons during laparoscopic surgery.

BACKGROUND: In the operating room (OR), nurse-surgeon coordination is essential to the success of a surgery. METHODS: This observational field study was conducted in the OR for selected laparoscopic surgeries to record surgery-related activities (SRAs) performed by the scrub nurses with different levels of OR experience. Those SRAs performed without instruction were defined as anticipatory movements. RESULTS: The scrub nurse spent 74% of OR time watching surgery and 35% of OR time performing SRAs. The intermediate skill nurses watch surgeon on 76% of the OR time and they performed 16 counts of anticipatory movements per procedure. Experienced nurses spent shorter amount of OR time (72%) watching surgery but they performed more anticipatory movements (20 counts) than the intermediate skill nurses. With basic cases, experienced and intermediate-skill nurses performed equal amounts of anticipatory movements; however, when assisting in complex cases, the experienced nurses performed significantly more anticipatory movements (24 counts) than the intermediate-skill nurses (16 counts). CONCLUSIONS: Experienced nurses develop sophisticated cognition during their careers in the OR, which allows them to maintain their involvement with the surgical team consistently. The anticipatory movement and the eye gaze are 2 valuable behavioral markers for assessing team performance.

Cognition and mortality from the major causes of death: the Health and Lifestyle Survey.

OBJECTIVE: To investigate the influence of reaction time and cognition on the risk of death from cause-specific mortality and to examine whether any association found remains after adjustment for available socioeconomic, lifestyle, and health factors. METHODS: Participants were from the UK Health and Lifestyle Survey. The sample consisted of 6424 community dwelling individuals aged between 18 and 97 years at baseline (1984/1985). Sociodemographic, lifestyle, health, and physiological information was collected alongside cognitive testing which included simple (SRT) and choice (CRT) reaction time, a short-term memory test, and a test of visual-spatial reasoning. Participants have been followed for 21 years for cause-specific mortality. RESULTS: Slower and more variable reaction times and poorer cognitive performance were associated with a higher risk of death from cardiovascular disease, stroke, and respiratory disease after controlling for age and sex. Slight attenuation was noted after adjustments for all covariates. However, only CRT mean remained significantly associated with death from respiratory disease. No associations were found for coronary heart disease, lung cancer, and all nonlung cancers. Significant cognition-mortality associations were mostly obtained in those aged over 60 years. The possibility of reverse causality was partly excluded by reanalysing the data after omitting individuals who died within 5 years of cognitive testing. CONCLUSIONS: Slower and more variable reaction times and poorer cognitive performance were related to an increased risk of mortality from cardiovascular disease, stroke, and respiratory disease. The possibility of reverse causality requires further testing.

Neuroticism, extraversion, and mortality in the UK Health and Lifestyle Survey: a 21-year prospective cohort study.

OBJECTIVE: To examine the influence of neuroticism and extraversion on all-cause and cause-specific mortality over 21 years after controlling for risk factors. METHODS: Participants were members of the Health and Lifestyle Survey, a British nationwide sample survey of 9003 adults. At baseline (1984 to 1985), individuals completed a sociodemographic and health questionnaire, underwent physical health examination, and completed the Eysenck Personality Inventory. Mortality was assessed for 21 years after baseline. A total of 5424 individuals had complete data. RESULTS: After controlling for age and gender, 1-standard deviation (SD) increase in neuroticism was related to 9% (hazard ratio (HR) = 1.09; 95% Confidence Interval (CI) = 1.03-1.16) increased risk of mortality from all causes. The association was nonsignificant (HR = 1.05; 95% CI = 0.99-1.11) after additionally controlling for occupational social class, education, smoking, alcohol consumption, physical activity, and health. There was 12% (HR = 1.12; 95% CI = 1.03-1.21) increased risk of death from cardiovascular disease associated with 1-SD increase in neuroticism. This was still significant after adjustment. When the sample was divided into 40- to 59-year-olds and those >or=60 years, neuroticism remained a significant risk for all-cause mortality and cardiovascular disease mortality; associations were nonsignificant after controlling for all covariates. Neuroticism was not associated with deaths from stroke, respiratory disease, lung cancer, or other cancers. Extraversion was protective of death from respiratory disease (HR = 0.84; 95% CI = 0.70- 1.00). CONCLUSIONS: After controlling for several risk factors, high neuroticism was significantly related to risk of death from cardiovascular disease. The effects of neuroticism on death from cardiovascular disease may be mediated by sociodemographic, health behavior, and physiological factors.