Advancing disability-inclusive climate research and action, climate justice, and climate-resilient development.

Globally, more than 1 billion people with disabilities are disproportionately and differentially at risk from the climate crisis. Yet there is a notable absence of climate policy, programming, and research at the intersection of disability and climate change. Advancing climate justice urgently requires accelerated disability-inclusive climate action. We present pivotal research recommendations and guidance to advance disability-inclusive climate research and responses identified by a global interdisciplinary group of experts in disability, climate change, sustainable development, public health, environmental justice, humanitarianism, gender, Indigeneity, mental health, law, and planetary health. Climate-resilient development is a framework for enabling universal sustainable development. Advancing inclusive climate-resilient development requires a disability human rights approach that deepens understanding of how societal choices and actions-characterised by meaningful participation, inclusion, knowledge diversity in decision making, and co-design by and with people with disabilities and their representative organisations-build collective climate resilience benefiting disability communities and society at large while advancing planetary health.

Martha's rule: applying a behaviour change framework to understand the potential of complementary roles of clinicians and patients in improving safety of patients deteriorating in hospital.

AIMS/BACKGROUND: Martha's rule stipulates the right of patients and their families to escalate care as a way to improve safety while in hospital. This article analyses the possible impact of the proposed policy through the lens of a behaviour change framework and explores new opportunities presented by the implementation of Martha's rule.. METHODS: A descriptive analysis was undertaken of interactions between patients, family, friends and clinicians during clinical deterioration in hospital. The capability-opportunity-motivation behaviour change framework was applied to understand reasons for failure to respond to deterioration. RESULTS: Care of deteriorating patients requires recording of vital signs, recognition of abnormalities, reporting through escalation and response by a competent clinician. Regarding the care of patients who deteriorate in hospital, healthcare professionals have capability and motivation to provide safe, high-quality care, but often lack the physical and social opportunity to report or respond through lack of time and peer pressure. Patients and family members have motivation and might have time to support safety systems. Martha's rule or similar arrangements allow healthcare organisations to create opportunities for patients and families to report and escalate care to experts in critical care when they recognise deterioration. CONCLUSIONS: The capability-opportunity-motivation behaviour change framework provides insights into the causes of failure to rescue in deteriorating patients and an argument for opportunities through escalation by patients and families through Martha's rule. This might reduce the number of system failures and enable safer care.

Understanding the immune profile of sudden infant death syndrome - proteomic perspectives.

AIM: The aim of this study was to investigate a panel of immune proteins in cases of sudden infant death syndrome (SIDS). It was hypothesised that, in at least a subset of SIDS, a dysregulated immune response may be a contributing factor leading to death. METHODS: The subjects included 46 SIDS cases and 41 controls autopsied at the Department of Forensic Sciences, Norway. The causes of death in the controls were accidents/trauma. Samples of cerebrospinal fluid (CSF) were analysed quantitatively by Proximity Extension Assay (PEA). RESULTS: Initial results revealed that normalised protein expression differed in 35 proteins. For the purposes of this report five proteins that are involved in immune system were selected for analysis: IFNLR1 (p = 0.003), IL10 (p = 0.007), IRAK4 (p < 0.001) and IL6 (p = 0.035); all had lower protein concentrations in SIDS cases compared to controls except for CD28 (p = 0.024) which had higher protein concentrations in SIDS cases. CONCLUSION: The results confirm previous studies indicating that a dysregulation of the immune system may be a predisposing factor for SIDS. The results may indicate that these aberrant protein concentrations could lead to an inadequate response to immune triggers and uncontrolled defence mechanisms towards the common cold or other non-fatal infections.

Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype that exhibits a high incidence of distant metastases and lacks targeted therapeutic options. Here we explored how the epigenome contributes to matrix metalloprotease (MMP) dysregulation impacting tumor invasion, which is the first step of the metastatic process. METHODS: We combined RNA expression and chromatin interaction data to identify insulator elements potentially associated with MMP gene expression and invasion. We employed CRISPR/Cas9 to disrupt the CCCTC-Binding Factor (CTCF) binding site on an insulator element downstream of the MMP8 gene (IE8) in two TNBC cellular models. We characterized these models by combining Hi-C, ATAC-seq, and RNA-seq with functional experiments to determine invasive ability. The potential of our findings to predict the progression of ductal carcinoma in situ (DCIS), was tested in data from clinical specimens. RESULTS: We explored the clinical relevance of an insulator element located within the Chr11q22.2 locus, downstream of the MMP8 gene (IE8). This regulatory element resulted in a topologically associating domain (TAD) boundary that isolated nine MMP genes into two anti-correlated expression clusters. This expression pattern was associated with worse relapse-free (HR = 1.57 [1.06 - 2.33]; p = 0.023) and overall (HR = 2.65 [1.31 - 5.37], p = 0.005) survival of TNBC patients. After CRISPR/Cas9-mediated disruption of IE8, cancer cells showed a switch in the MMP expression signature, specifically downregulating the pro-invasive MMP1 gene and upregulating the antitumorigenic MMP8 gene, resulting in reduced invasive ability and collagen degradation. We observed that the MMP expression pattern predicts DCIS that eventually progresses into invasive ductal carcinomas (AUC = 0.77, p < 0.01). CONCLUSION: Our study demonstrates how the activation of an IE near the MMP8 gene determines the regional transcriptional regulation of MMP genes with opposing functional activity, ultimately influencing the invasive properties of aggressive forms of breast cancer.

Discordant and false-negative interpretations at digital breast tomosynthesis in the prospective Oslo Tomosynthesis Screening Trial (OTST) using independent double reading.

OBJECTIVES: To analyze discordant and false-negatives of double reading digital breast tomosynthesis (DBT) versus digital mammography (DM) including reading times in the Oslo Tomosynthesis Screening Trial (OTST), and reclassify these in a retrospective reader study as missed, minimal sign, or true-negatives. METHODS: The prospective OTST comparing double reading DBT vs. DM had paired design with four parallel arms: DM, DM + computer aided detection, DBT + DM, and DBT + synthetic mammography. Eight radiologists interpreted images in batches using a 5-point scale. Reading time was automatically recorded. A retrospective reader study including four radiologists classified screen-detected cancers with at least one false-negative score and screening examinations of interval cancers as negative, non-specific minimal sign, significant minimal sign, and missed; the two latter groups are defined "actionable." Statistics included chi-square, Fisher's exact, McNemar's, and Mann-Whitney U tests. RESULTS: Discordant rate (cancer missed by one reader) for screen-detected cancers was overall comparable (DBT (31% [71/227]) and DM (30% [52/175]), p = .81), significantly lower at DBT for spiculated cancers (DBT, 19% [20/106] vs. DM, 36% [38/106], p = .003), but high (28/49 = 57%, p = 0.001) for DBT-only detected spiculated cancers. Reading time and sensitivity varied among readers. False-negative DBT-only detected spiculated cancers had shorter reading time than true-negatives in 46% (13/28). Retrospective evaluation classified the following DBT exams "actionable": three missed by both readers, 95% (39/41) of discordant cancers detected by both modes, all 30 discordant DBT-only cancers, 25% (13/51) of interval cancers. CONCLUSIONS: Discordant rate was overall comparable for DBT and DM, significantly lower at DBT for spiculated cancers, but high for DBT-only detected spiculated lesions. Most false-negative screen-detected DBT were classified as "actionable." CLINICAL RELEVANCE STATEMENT: Retrospective evaluation of false-negative interpretations from the Oslo Tomosynthesis Screening Trial shows that most discordant and several interval cancers could have been detected at screening. This underlines the potential for modern AI-based reading aids and triage, as high-volume screening is a demanding task. KEY POINTS: • Digital breast tomosynthesis (DBT) screening is more sensitive and has higher specificity compared to digital mammography screening, but high-volume DBT screening is a demanding task which can result in high discordance rate among readers. • Independent double reading DBT screening had overall comparable discordance rate as digital mammography, lower for spiculated masses seen on both modalities, and higher for small spiculated cancer seen only on DBT. • Almost all discordant digital breast tomosynthesis-detected cancers (72 of 74) and 25% (13 of 51) of the interval cancers in the Oslo Tomosynthesis Screening Trial were retrospectively classified as actionable and could have been detected by the readers.

EXPERIMENTAL INFECTIONS WITH EUHAPLORCHIS CALIFORNIENSIS AND A SMALL CYATHOCOTYLID INCREASE CONSPICUOUS BEHAVIORS IN CALIFORNIA KILLIFISH (FUNDULUS PARVIPINNIS).

Some parasites manipulate their host's phenotype to enhance predation rates by the next host in the parasite's life cycle. Our understanding of this parasite-increased trophic transmission is often stymied by study-design challenges. A recurring difficulty has been obtaining uninfected hosts with a coevolutionary history with the parasites, and conducting experimental infections that mimic natural processes. In 1996, Lafferty and Morris provided what has become a classic example of parasite-increased trophic transmission; they reported a positive association between the intensity of a brain-infecting trematode (Euhaplorchis californiensis) in naturally infected California killifish (Fundulus parvipinnis) and the frequency of conspicuous behaviors, which was thought to explain the documented 10-30× increase in predation by the final host birds. Here, we address the primary gap in that study by using experimental infections to assess the causality of E. californiensis infection for increased conspicuous behaviors in F. parvipinnis. We hatched and reared uninfected F. parvipinnis from a population co-occurring with E. californiensis, and infected them 1-2 times/week over half their life span with E. californiensis and a small cyathocotylid trematode (SMCY) that targets the host's muscle tissue. At 3 time points throughout the hosts' lives, we quantified several conspicuous behaviors: contorting, darting, scratching, surfacing, and vertical positioning relative to the water's surface. Euhaplorchis californiensis and SMCY infection caused 1.8- and 2.5-fold overall increases in conspicuous behaviors, respectively. Each parasite was also associated with increases in specific conspicuous behaviors, particularly 1.9- and 1.4-fold more darting. These experimental findings help solidify E. californiensis-F. parvipinnis as a classic example of behavioral manipulation. Yet our findings for E. californiensis infection-induced behavioral change were less consistent and strong than those previously documented. We discuss potential explanations for this discrepancy, particularly the idea that behavioral manipulation may be most apparent when fish are actively attacked by predators. Our findings concerning the other studied trematode species, SMCY, highlight that trophically transmitted parasites infecting various host tissues are known to be associated with conspicuous behaviors, reinforcing calls for research examining how communities of trophically transmitted parasites influence host behavior.

Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts.

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma.

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells. Surprisingly, myoepithelial disruption was more advanced in DCIS patients that did not develop IBC, suggesting this process could be protective against recurrence. Taken together, this HTAN Breast PreCancer Atlas study offers insight into drivers of IBC relapse and emphasizes the importance of the TME in regulating these processes.

Trends in Disability-Free Life Expectancy (DFLE) from 1995 to 2017 in the older Norwegian population by sex and education: The HUNT Study.

AIM: Understanding whether increasing Life Expectancy (LE) translates to improved health and function among older adults is essential, but results are inconclusive. We aimed to estimate trends in Disability-Free Life Expectancy (DFLE) in the older Norwegian population by sex and education from 1995 to 2017. METHOD: National life table data were combined with cross-sectional data on functional ability for 70+ year-olds from the population-based Trøndelag Health Surveys 2-4 (1995-1997, 2006-2008 and 2017-2019) (n=24,733). Self-reported functional ability was assessed on a graded scale by a combination of Instrumental Activities of Daily Living (IADL) such as paying bills, going out or shopping (mild disability) and Personal Activities of Daily Living (PADL) such as washing, dressing or eating (severe disability). LE, DFLE, Mild-Disability LE and Severe-Disability LE at age 70 were estimated by the Sullivan method. RESULTS: From 1995 to 2017 DFLE at age 70 increased from 8.4 to 13.0 years in women, and from 8.0 to 12.1 years in men. DFLE increased in the basic and high educational groups, but more so in the high educational group among men. Educational inequalities in years spent with disability however, remained low. CONCLUSIONS: From the mid-1990s and over the past three decades both LE and DFLE at 70 years increased in the older Norwegian population, for both men and women, and across basic and high educational levels. Educational inequalities in DFLE increased, especially in men, but years spent with disability were similar across the three decades.

Influenza hospitalizations during childhood in children born preterm.

OBJECTIVE: The objective is to determine if children born preterm were at increased risk of influenza hospitalization up to age five. METHODS: National registry data on all children born in Norway between 2008 and 2011 were used in Cox regression models to estimate adjusted hazard ratios (aHRs) for influenza hospitalizations up to age five in children born preterm (<37 pregnancy weeks). HRs were also estimated separately for very preterm (<32 weeks), early term (37-38 weeks), and post-term (≥42 weeks) children. RESULTS: Among 238,628 children born in Norway from January 2008 to December 2011, 15,086 (6.3%) were born preterm. There were 754 (0.3%) children hospitalized with influenza before age five. The rate of hospitalizations in children born preterm was 13.8 per 10,000 person-years (95% confidence interval [CI] [11.3, 16.7]), and 5.9 per 10,000 person-years (95% CI [5.5, 6.4]) in children born at term (≥37 weeks). Children born preterm had a higher risk of influenza hospitalization before age 5: aHR 2.33 (95% CI [1.85, 2.93]). The risk increased with decreasing gestational age and was highest among those born extremely/very preterm; aHR 4.07 (95% CI [2.63, 6.31]). Compared with children born at 40-41 weeks, children born early term also had an elevated risk of influenza hospitalization; aHR (37 weeks) 1.89 (95% CI [1.43, 2.50]), aHR (38 weeks) 1.43 (95% CI [1.15, 1.78]). CONCLUSION: Children born preterm had a higher risk of influenza hospitalizations before age five. An elevated risk was also present among children born at an early term. Children born preterm could benefit from influenza vaccinations.

On CRDPs and CRPD: why the rights of people with disabilities are crucial for understanding climate-resilient development pathways.

In this Personal View, we examine how the Convention on the Rights of Persons with Disabilities and lived experiences of disability can deepen understanding of four key features of climate-resilient development: social justice and equity as normative goals; the ethical underpinnings of social choices; the inequitable relations that drive marginalisation; and the ways in which society navigates uncertainty through inclusive and contestatory politics. A disability lens not only helps to understand how marginalisation generates vulnerability; it also helps to elaborate the ethic of solidarity as underpinning social choices and steering development towards climate-resilient pathways. Social justice concerns non-discrimination and equitable participation in everyday informal arenas, as well as formal decision making processes. The resilience knowledges of disabled people help to rethink sustainable development by expounding human interdependence and everyday problem solving in the face of uncertainties. They also contribute to opening up climate change decision making and knowledge processes in ways crucial to engendering transformative change. Embracing human diversity by recognising dignity and capacity is required to counter othering and marginalisation, ensure human wellbeing and planetary health, and achieve socially just development. As such, solidarity is not just a normative goal, but also a means of building climate-resilient development.

Adverse Childhood Experiences Among 28,047 Norwegian Adults From a General Population.

Aim: The purpose of this study was to estimate the prevalence of adverse childhood experiences (ACEs) among Norwegian adults from a general population and to identify potential associations with demographic and socioeconomic characteristics. Methods: A randomly drawn sample (N = 61,611) from the public registry of inhabitants was invited to participate in the Norwegian Counties Public Health Survey. The present study was based on online responses from 28,047 adults ≥18 years (mean age: 46.9 years, SD = 16.03). Log-link binomial regression analyses were performed to examine associations between four measures of ACEs (family conflict, lack of adult support, bad memories, and difficult childhood) and demographic (age, gender, civil status, parental divorce) and socioeconomic characteristics (education level, perceived financial situation, and welfare benefits). Results: Single individuals and those with parents that divorced during childhood were at elevated risk of all four ACEs. The risk varied to some degree between the sexes. The prevalence of ACEs declined with increasing age. We found a consistent social gradient that corresponded to the frequency of ACEs for all three socioeconomic characteristics investigated. The risks were highest for those in the lowest socioeconomic levels (RR: 1.53, 95% CI: 1.32-1.78 to RR: 4.95, CI: 4.27-5.74). Conclusions: Public health strategies should direct more attention to the interplay between ACEs and socioeconomic factors. Welfare services should be sensitive to ACEs among their service recipients.

Prevalence of Parental Alcohol Problems among a General Population Sample of 28,047 Norwegian Adults: Evidence for a Socioeconomic Gradient.

The aim of the study presented here was to estimate the prevalence of parental alcohol problems during childhood in a general population of Norwegian adults, and to investigate associations between parental alcohol problems during childhood and lower socioeconomic status in adulthood. This cross-sectional study recruited 28,047 adults (≥18 years) to an online health survey (Norwegian Counties Public Health Surveys). We evaluated demographic and socioeconomic measures and responses to a shortened version of the Children of Alcoholics Screening Test (CAST-6) scale to assess whether respondents perceived parental alcohol consumption during childhood as problematic. Respondents reported parental alcohol problems at a rate of 15.6%, but the experience was more prevalent among adults with a low education (20.0%), compared to those with intermediate (16.4%) or high educations (13.8%, χ2(2) = 87.486, p < 0.001), and it was more common among respondents with low economic capabilities (21.1%) compared to those with middle/high capabilities (14.2%, χ2(1) = 162.089, p < 0.001). Parental alcohol problems were most prevalent among respondents that received welfare benefits (24.5%). Multivariable logistic regression analyses revealed associations between parental alcohol problems and low socioeconomic status in adulthood; odds ratios (95% confidence intervals) ranged from 1.33 (1.25-1.42) to 1.89 (1.72-2.06). From a public health perspective, children who grow up with parental alcohol problems should be reached through both universal and selective interventions.

FRMD6 has tumor suppressor functions in prostate cancer.

Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6 (FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6 knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6 deficient PC cells. Finally, we established orthotropic Frmd6 and Pten, or Pten only (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Pten double knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Pten single-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6 was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.

Gene expression profile in cases of infectious death in infancy.

BACKGROUND: Genetic predispositions in cases suffering sudden unexpected infant death have been a research focus worldwide during the past decade. Despite large efforts, there is still uncertainty concerning the molecular pathogenesis of these deaths. With genetic technology in constant development, the possibility of an alternative approach into this research field has become available, like mRNA expression studies. METHODS: In this study, we investigated mRNA gene expression in 14 cases who died suddenly and unexpectedly from infection without a history of severe illness prior to death. The control group included eight accidents, two cases of natural death, one undetermined, one case of medical malpractice, and two homicides. The study included tissue from liver, heart, and brain using Illumina whole-genome gene expression assay. RESULTS: From the array, 19 genes showed altered expression in the infectious deaths compared to controls. Tissue from the heart showed 15 genes with altered mRNA expression compared to the control group. CONCLUSIONS: Downregulation of KCNE5 in heart tissue from cases of infectious death was of particular interest. Variants of KCNE5 are associated with Brugada syndrome and sudden death and could be responsible for the fatal outcome in the group of infectious death. IMPACT: KCNE5 is downregulated in tissue from the heart in cases of infectious death in infancy. This study provides knowledge about the gene expression profile in cases of infectious death. Variants of a gene known to give increased risk of cardiac arrhythmia is downregulated in cases of infectious death in infancy. The results could give us better knowledge as to why some infants do not survive an infection. This study provides a candidate gene for future studies.

Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome.

Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.

Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential.

Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: DOCK2,HAPLN3, and FBXO30 (specificity/sensitivity: 80%-100%/75-94%). These candidates were further analyzed in plasma samples from 36 healthy controls, 61 benign prostatic hyperplasia (BPH), 102 localized PCa, and 65 de novo mPCa patients using methylation-specific droplet digital PCR. Methylated ctDNA for DOCK2/HAPLN3/FBXO30 was generally not detected in healthy controls, BPH patients, nor in patients with localized PCa despite a positive signal in 98%-100% of matched radical prostatectomy tissue samples. However, ctDNA methylation of DOCK2,HAPLN3, and/or FBXO30 was detected in 61.5% (40/65) of de novo mPCa patients and markedly increased in high- compared to low-volume mPCa (89.3% (25/28) vs. 32.1% (10/31), p < 0.001). Moreover, detection of methylated ctDNA was associated with significantly shorter time to progression to metastatic castration resistant PCa, independent of tumor-volume. These results indicate that methylated ctDNA (DOCK2/HAPLN3/FBXO30) may be potentially useful for identification of hormone-naïve mPCa patients who could benefit from intensified treatment.

Prevalence, clustering and combined effects of lifestyle behaviours and their association with health after retirement age in a prospective cohort study, the Nord-Trøndelag Health Study, Norway.

BACKGROUND: Lifestyle behaviours are potential risk factors for disease and mortality, but less is known about the association with health in retirement age. The aim of this paper was to study the prevalence, clustering and combined effects of lifestyle behaviours and their association with health outcomes in the first decade after retirement in a Norwegian cohort. METHODS: Participants were 55-64-year-olds at baseline in the Nord-Trøndelag Health Survey 2 (HUNT2, 1995-97) who also participated in HUNT3 (2006-08). Logistic regression analyses were used to investigate the association of daily smoking, physical inactivity, risky alcohol consumption, disturbed sleep duration, excessive sitting time and low social participation before retirement with self-rated health (n = 4022), life satisfaction (n = 5134), anxiety (n = 4461) and depression (n = 5083) after retirement, 11 years later. RESULTS: Low social participation and physical inactivity were the most prevalent lifestyle behaviours (41.1 and 40.6%). Risky alcohol consumption and disturbed sleep were the lifestyle behaviours most strongly associated with poor self-rated health, poor life satisfaction and anxiety after retirement (OR's = 1.39-1.92). Physical inactivity was additionally associated with depression (OR = 1.44 (1.12-1.85)). Physical inactivity had the largest population attributable fractions for reducing poor self-rated health and depression (14.9 and 8.8%). An increasing number of lifestyle risk behaviours incrementally increased the risk for the adverse health outcomes. CONCLUSIONS: Risky alcohol consumption and disturbed sleep duration were most strongly associated with poor health outcomes after retirement age. On a population level, increased physical activity before retirement had the largest potential for reducing adverse health outcomes after retirement age.