Increased risk of suicide in New South Wales men with prostate cancer: Analysis of linked population-wide data

© 2018 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background An elevated risk of suicide after a diagnosis of prostate cancer has been reported previously in the USA and Sweden. We aimed to identify whether prostate cancer survivors resident in New South Wales Australia are at higher risk of suicide and if so, who is most at risk. Methods Data were obtained from the New South Wales (NSW) Cancer Registry for all men diagnosed with prostate cancer in NSW during 1997 to 2007. These were linked by the Centre for Health Record Linkage (CHeReL) to Australian Bureau of Statistics Mortality Data to the end of 2007 to determine vital status and cause of death. We compared the number of suicides observed for prostate cancer survivors with the expected number of suicides based on age- and calendar year- specific rates for the NSW Male population using standardised mortality ratios (SMRs). Suicide rate ratios (RR) by disease and patients' characteristics were estimated using multivariable negative binomial regression to determine the most at risk groups. Results During the study period 51,924 NSW men were diagnosed with prostate cancer. Forty nine of these men were subsequently recorded as committing suicide up to 10 years after diagnosis with an SMR of 1.70 (95% CI:1.26±2.25). Twenty six (53%) of these suicides occurred within 12 months after diagnosis. Risk diminished over time since diagnosis (RR in 1±2 years after diagnosis = 0.29, 95% CI: 0.12±0.71, 2±4 years RR = 0.30, 95% CI: 0.14±0.16 and 4+ years RR = 0.26, 95% CI: 0.11±0.60 compared with <1 year since diagnosis). Men with non-localised disease had a higher risk of suicide compared to men with localised disease (RR = 2.68, 95% CI: 1.15±6.23). Men living outside major cities had lower risk of suicide compared to those resident in major cities (rate ratio = 0.42, 95% CI: 0.20±0.87). Single, divorced, widowed or separated men were more likely to commit suicide than married men (RR = 4.18, 95% CI: 2.36±7.42). Conclusion Risk of suicide is higher for NSW men diagnosed with prostate cancer than the general age matched Male population. Vulnerable or lonely men and those with pre-existing depression or suicidal ideation who are diagnosed with prostate cancer should be offered additional psychological support

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

This is the final version of the article. Available from the publisher via the DOI in this record.Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

A mass media campaign are needed to counter misconceptions about back pain and promote higher value care.

Back pain is saddled by misconceptions that contribute to low-value care and poor outcomes. Many patients and clinicians mistakenly view the spine as fragile, believe that pain equates to damage, and over-emphasise the role and value of rest, imaging, medication, and surgery.1 Guideline-based care will not be embraced if such misconceptions are not countered. Here we provide four arguments for accessible, engaging and convincing education to the public and health professionals

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Using linked routinely collected health data to describe prostate cancer treatment in New South Wales, Australia: a validation study

<p>Abstract</p> <p>Background</p> <p>Population-based patterns of care studies are important for monitoring cancer care but conducting them is expensive and resource-intensive. Linkage of routinely collected administrative health data may provide an efficient alternative. Our aim was to determine the accuracy of linked routinely collected administrative data for monitoring prostate cancer care in New South Wales (NSW), Australia.</p> <p>Methods</p> <p>The NSW Prostate Cancer Care and Outcomes Study (PCOS), a population-based survey of patterns of care for men aged less than 70 years diagnosed with prostate cancer in NSW, was linked to the NSW Cancer Registry, electronic hospital discharge records and Medicare and Pharmaceutical claims data from Medicare Australia. The main outcome measures were treatment with radical prostatectomy, any radiotherapy, external beam radiotherapy, brachytherapy or androgen deprivation therapy, and cancer staging. PCOS data were considered to represent the true treatment status. The sensitivity and specificity of the administrative data were estimated and relevant patient characteristics were compared using chi-squared tests.</p> <p>Results</p> <p>The validation data set comprised 1857 PCOS patients with treatment information linked to Cancer Registry records. Hospital and Medicare claims data combined described treatment more accurately than either one alone. The combined data accurately recorded radical prostatectomy (96% sensitivity) and brachytherapy (93% sensitivity), but not androgen deprivation therapy (76% sensitivity). External beam radiotherapy was rarely captured (5% sensitivity), but this was improved by including Medicare claims for radiation field setting or dosimetry (86% sensitivity). False positive rates were near 0%. Disease stage comparisons were limited by one-third of cases having unknown stage in the Cancer Registry. Administrative data recorded treatment more accurately for cases in urban areas.</p> <p>Conclusions</p> <p>Cancer Registry and hospital inpatient data accurately captured radical prostatectomy and brachytherapy treatment, but not external beam radiotherapy or disease stage. Medicare claims data substantially improved the accuracy with which all major treatments were recorded. These administrative data combined are valid for population-based studies of some aspects of prostate cancer care.</p

TNF-α induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide

BACKGROUND: MAdCAM-1 is an adhesion molecule expressed in Peyer's patches and lymphoid tissues which is mobilized by cytokines like TNF-α and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-α. METHODS: To examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-α, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-α-stimulation, and measured MAdCAM-1 induction at 24 h. RESULTS AND DISCUSSION: DETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-α-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-α regulated MAdCAM-1 expression. CONCLUSIONS: Exogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines