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Objective: To assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones., Design: Nationwide register based emulated target trial., Setting: Swedish national registries., Participants: 919 614 women aged 50-58 between 2007 and 2020 without hormone therapy use in the previous two years, identified from the Swedish population., Interventions: 138 nested trials were designed, starting each month from July 2007 until December 2018. Using the prescription registry data for that specific month, women who had not used hormone therapy in the previous two years were assigned to one of eight treatment groups: oral combined continuous, oral combined sequential, oral unopposed oestrogen, oral oestrogen with local progestin, tibolone, transdermal combined, transdermal unopposed oestrogen, or non-initiators of menopausal hormone therapy., Main Outcome Measures: Hazard ratios with 95% confidence intervals were estimated for venous thromboembolism, as well as for ischaemic heart disease, cerebral infarction, and myocardial infarction separately and as a composite cardiovascular disease outcome. Treatment effects were estimated by contrasting initiators and non-initiators in observational analogues to "intention-to-treat" analyses and continuous users versus never users in "per protocol" analyses., Results: A total of 77 512 women were initiators of any menopausal hormone therapy and 842 102 women were non-initiators. 24 089 women had an event recorded during the follow-up: 10 360 (43.0%) had an ischaemic heart disease event, 4098 (17.0%) had a cerebral infarction event, 4312 (17.9%) had a myocardial infarction event, and 9196 (38.2%) had a venous thromboembolic event. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (hazard ratio 1.52, 95% confidence interval 1.11 to 2.08) compared with non-initiators. Initiators of tibolone or oral oestrogen-progestin therapy had a higher risk of ischaemic heart disease (1.46 (1.00 to 2.14) and 1.21 (1.00 to 1.46), respectively). A higher risk of venous thromboembolism was observed for oral continuous oestrogen-progestin therapy (1.61, 1.35 to 1.92), sequential therapy (2.00, 1.61 to 2.49), and oestrogen-only therapy (1.57, 1.02 to 2.44). Additional results in per protocol analyses showed that use of tibolone was associated with a higher risk of cerebral infarction (1.97, 1.02 to 3.78) and myocardial infarction (1.94, 1.01 to 3.73)., Conclusions: Use of oral oestrogen-progestin therapy was associated with an increased risk of heart disease and venous thromboembolism, whereas the use of tibolone was associated with an increased risk of ischaemic heart disease, cerebral infarction, and myocardial infarction but not venous thromboembolism. These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding for the study as detailed above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Since the development of the Death Literacy Index (DLI) in 2019 in Australia, subsequent internationally validated versions have prompted rewording and refinement of the original survey questions. Use of the DLI in the community has also resulted in requests for a short format., Objectives: To examine and report on the psychometric properties of a revised version of the DLI-R and develop a short format DLI-9., Design: A cross-sectional national survey was conducted for the validation of the revised DLI., Methods: The DLI items were revised by the research team using the international literature. DLI data were collected from a representative online non-probability panel of 1202 Australian adults, based on age, gender, and geographical location. Confirmatory factor analysis (CFA) was conducted to ensure the revised version (DLI-R) was consistent with the original. To develop a short format version of the DLI (DLI-9), items were first removed based on face validity, followed by an exploratory factor analysis (EFA) and CFA. The internal reliability of the DLI-R and the DLI-9 was assessed using Cronbach's alpha. The intraclass correlation coefficient was calculated to examine the inter-rater reliability between the DLI-R and DLI-9., Results: Twenty-four questions in the DLI were reworded for clarity. A CFA on the 29 items of this modified version of the DLI indicated a good model fit (Tucker-Lewis Index (TLI): 0.93; Comparative Fit Index (CFI): 0.93; root mean square of approximation (RMSEA): 0.06; standardized root mean residual (SRMR): 0.06), with six latent variables and an underlying latent variable "death literacy." For the DLI-9, an EFA identified a nine-item, two-factor structure model (DLI-9). A subsequent CFA in a separate sample demonstrated a good model fit for the DLI-9 (TLI: 0.92; CFI: 0.94; RMSEA: 0.089; SRMR: 0.07). Excellent inter-rater reliability (0.98) was observed between DLI-9 and DLI-R. Cronbach's alpha coefficients for DLI-R scales and subscales and the DLI-9 all exceeded 0.8, indicating high internal consistency., Conclusion: The DLI-R and the DLI-9 were found to have acceptable psychometric properties. The development of a shorter version of the DLI provides a valid measure of overall death literacy., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objectives: Oral contraceptives (OC) and menopausal hormone therapy (MHT) contain exogenous sex hormones and are used by millions of women around the world. However, their effect on the development of rheumatoid arthritis (RA) is still debated and the current literature suggests that they may exert opposite effects on the risk of RA. The present study aimed to estimate the effects of exogenous hormones on the development of RA, both during the reproductive lifespan and later in life., Methods: The association between OC and RA, as well as between MHT and late-onset RA (LORA), was investigated using time-dependent Cox regression modelling in white British women from the UK Biobank (n = 236 602 and n = 102 466, respectively) and replicated in women from all ethnic groups., Results: OC use was associated with a decreased risk of RA in ever-users [hazard ratio (HR) = 0.89; 95% CI = 0.82-0.96], as well as in current (HR = 0.81; 0.73-0.91) and former users (HR = 0.92; 0.84 -1.00), compared with never-users. In contrast, MHT use was associated with an increased risk of LORA in ever-users (HR = 1.16; 1.06-1.26) as well as in former users (HR = 1.13; 1.03-1.24) compared with never-users., Conclusion: OC use appears to protect against RA, while MHT may increase the risk of LORA. This study provides new insights into the possible inverse effect of exposure to different exogenous sex hormones on the risk of RA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: People with palliative care needs and their carers often rely on out-of-hours services to remain at home. Policymakers have recommended implementing telephone advice lines to ensure 24/7 access to support. However, the impact of these services on patient and carer outcomes, as well as the health care system, remains poorly understood., Aim: To evaluate the clinical- and cost-effectiveness of out-of-hours palliative care telephone advice lines, and to identify service characteristics associated with effectiveness., Design: Rapid systematic review (PROSPERO ID: CRD42023400370) with narrative synthesis., Data Sources: Three databases (Medline, EMBASE and CINAHL) were searched in February 2023 for studies of any design reporting on telephone advice lines with at least partial out-of-hours availability. Study quality was assessed using the Mixed Methods Appraisal Tool, and quantitative and qualitative data were synthesised narratively., Results: Twenty-one studies, published 2000-2022, were included. Most studies were observational, none were experimental. While some evidence suggested that telephone advice lines offer guidance and reassurance, supporting care at home and potentially reducing avoidable emergency care use in the last months of life, variability in reporting and poor methodological quality across studies limit our understanding of patient/carer and health care system outcomes., Conclusion: Despite their increasing use, evidence for the clinical- and cost-effectiveness of palliative care telephone advice lines remains limited, primarily due to the lack of robust comparative studies. There is a need for more rigorous evaluations incorporating experimental or quasi-experimental methods and longer follow-up, and standardised reporting of telephone advice line models and outcomes, to guide policy and practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Telephone advice lines have been recommended internationally to support around-the-clock care for people living at home with advanced illness. While they undoubtedly support care, there is little evidence about what elements are needed for success. A national picture is needed to understand, improve and standardise service delivery/care., Aim: To explore telephone advice lines for people living at home with advanced illness across the four UK nations, and to construct a practical framework to improve services., Design: A cross-national evaluation of telephone advice lines using structured qualitative interviews. A patient and public involvement workshop was conducted to refine the framework., Setting/participants: Professionals with responsibilities for how palliative care services are delivered and/or funded at a local or regional level, were purposively sampled., Results: Seventy-one interviews were conducted, covering 60 geographical areas. Five themes were identified. Availability : Ten advice line models were described. Variation led to confusion about who to call and when. Accessibility, awareness and promotion : It was assumed that patients/carers know who to call out-of-hours, but often they did not. Practicalities : Call handlers skills/expertise varied, which influenced how calls were managed. Possible responses ranged from signposting to organising home visits. Integration/continuity of care : Integration between care providers was limited by electronic medical records access/information sharing. Service structure/commissioning : Sustained funding was often an issue for charitably funded organisations., Conclusions: Our novel evidence-based practical framework could be transformative for service design/delivery, as it presents key considerations relating to the various elements of advice lines that may impact on the patient/carer experience., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: More than 150 million women worldwide use oral contraceptives. Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V Leiden and the prothrombin, are at an increased risk for venous thromboembolism, especially when combined with oral contraceptive use. Venous thromboembolism is a complex disorder involving many genetic risk factors, and recently, polygenic risk scores have been proposed to capture a significant proportion of the genetic risk of venous thromboembolism., Objective: The aim of this study was to estimate the risk for developing venous thromboembolism when initiating oral contraceptive use (first 2 years) and during continued use among women with a high genetic liability., Study Design: We used a prospective study design in which 244,420 participants from the UK Biobank were followed from birth. The effect of oral contraceptive use during the first 2 years and in the remaining years of oral contraceptive use on the risk of developing venous thromboembolism was estimated using a Cox regression with a time-dependent exposure variable. Women were stratified according to their polygenic risk scores and whether they were carriers of factor V Leiden and/or prothrombin variants., Results: When genetic risk was not considered, an increased risk for venous thromboembolism was observed during the first 2 years of oral contraceptive use (hazard ratio, 3.09; 95% confidence interval, 3.00-3.20) but not during continued use (hazard ratio, 0.92; 95% confidence interval, 0.80-1.05). However, when genetic risk was considered, women in the highest polygenic risk score category had a more pronounced risk of developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 6.35; 95% confidence interval, 4.98-8.09), and a high risk was also observed among factor V Leiden (hazard ratio, 5.73; 95% confidence interval, 5.31-6.17) and prothrombin variant carriers (hazard ratio, 5.23; 95% confidence interval, 4.67 - 5.87). A high polygenic risk score in combination with being a factor V Leiden and prothrombin variant carrier conferred the highest risk for developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 14.8; 95% confidence interval, 9.28-23.6). Women with a high genetic liability also had an increased risk during continued use but it was less pronounced, and the highest risk was conferred to carriers of both factor V Leiden and the prothrombin variant (hazard ratio, 4.93; 95% confidence interval, 3.16-7.7)., Conclusion: Evaluating polygenic risk can identify additional venous thromboembolism risk that is not captured in the commonly investigated genes for inherited thrombophilia. Our results indicate that oral contraceptive use is associated with an increased risk for developing a venous thromboembolism, particularly among women with a high genetic predisposition, and that oral contraceptive use dramatically increases the risk thereof short after initiation of use, which decreases with continued use. This suggests that the polygenic risk score could be used to identify women who are at high risk for developing a venous thromboembolism and advise them on alternative methods of contraception., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The detection of oligonucleotides is a central step in many biomedical investigations. The most commonly used methods for detecting oligonucleotides often require concentration and amplification before detection. Therefore, developing detection methods with a direct read-out would be beneficial. Although commonly used for the detection of amplified oligonucleotides, fluorescent molecular beacons have been proposed for such direct detection. However, the reported limits of detection using molecular beacons are relatively high, ranging from 100 nM to a few µM, primarily limited by the beacon fluorescence background. In this study, we enhanced the relative signal contrast between hybridized and non-hybridized states of the beacons by immobilizing them on lightguiding nanowires. Upon hybridization to a complementary oligonucleotide, the fluorescence from the surface-bound beacon becomes coupled in the lightguiding nanowire core and is re-emitted at the nanowire tip in a narrower cone of light compared with the standard 4π emission. Prior knowledge of the nanowire positions allows for the continuous monitoring of fluorescence signals from each nanowire, which effectively facilitates the discrimination of signals arising from hybridization events against background signals. This resulted in improved signal-to-background and signal-to-noise ratios, which allowed for the direct detection of oligonucleotides at a concentration as low as 0.1 nM.

The death literacy index (DLI) was developed in Australia to measure death literacy, a set of experience-based knowledge needed to understand and act on end-of-life (EOL) care options but has not yet been validated outside its original context. The aim of this study was to develop a culturally adapted Swedish-language version of the DLI, the DLI-S, and assess sources of evidence for its validity in a Swedish context. The study involved a multi-step process of translation and cultural adaptation and two validation phases: examining first content and response process validity through expert review (n = 10) and cognitive interviews (n = 10); and second, internal structure validity of DLI-S data collected from an online cross-sectional survey (n = 503). The psychometric evaluation involved analysis of descriptive statistics on item and scale-level, internal consistency and test-retest reliability, and confirmatory factor analysis. During translation and adaptation, changes were made to adjust items to the Swedish context. Additional adjustments were made following findings from the expert review and cognitive interviews. The content validity index exceeded recommended thresholds (S-CVIAve = 0.926). The psychometric evaluation provided support for DLI-S' validity. The hypothesized six-factor model showed good fit (χ2 = 1107.631 p<0.001, CFI = 0.993, TLI = 0.993, RMSEA = 0.064, SRMR = 0.054). High internal consistency reliability was demonstrated for the overall scale (Cronbach's α = 0.94) and each sub-scale (α 0.81-0.92). Test-retest reliability was acceptable, ICC ranging between 0.66-0.85. Through a comprehensive assessment of several sources of evidence, we show that the DLI-S demonstrates satisfactory validity and acceptability to measure death literacy in the Swedish context. There are, however, indications that the sub-scales measuring community capacity perform worse in comparison to other sca and may function differently in Sweden than in the original context. The DLI-S has potential to contribute to research on community-based EOL interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Johansson 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.)

Objective: Anxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions., Method: Patients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types., Results: Results suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder., Conclusion: Our four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders., (© 2023 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Introduction: Deep vein thrombosis (DVT) is a complex disease, where 60 % of risk is due to genetic factors, such as the Factor V Leiden (FVL) variant. DVT is either asymptomatic or manifests with unspecific symptoms and, if left untreated, DVT leads to severe complications. The impact is dramatic and currently, there is still a research gap in DVT prevention. We characterized the genetic contribution and stratified individuals based on genetic makeup to evaluate if it favorably impacts risk prediction., Methods: In the UK Biobank (UKB), we performed gene-based association tests using exome sequencing data, as well as a genome-wide association study. We also constructed polygenic risk scores (PRS) in a subset of the cohort (Number of cases = 8231; Number of controls = 276,360) and calculated the impact on the prediction capacity of the PRS in a non-overlapping part of the cohort (Number of cases = 4342; Number of controls = 142,822). We generated additional PRSs that excluded the known causative variants., Results: We discovered and replicated a novel common variant (rs11604583) near the region where are located the TRIM51 and LRRC55 genes and identified a novel rare variant (rs187725533) located near the CREB3L1 gene, associated with 2.5-fold higher risk of DVT. In one of the PRS models constructed, the top decile of risk is associated with 3.4-fold increased risk, an effect that is 2.3-fold when excluding FVL carriers. In the top PRS decile, the cumulative risk of DVT at the age of 80 years is 10 % for FVL carriers, contraposed to 5 % for non-carriers. The population attributable fractions of having a high polygenic risk on the rate of DVT was estimated to be around 20 % in our cohort., Conclusion: Individuals with a high polygenic risk of DVT, and not only carriers of well-studied variants such as FVL, may benefit from prevention strategies., Competing Interests: Declaration of competing interest The authors report that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Death literacy is a recent conceptualization representing both individual and community competence, for example, a set of knowledge and skills for engaging in end-of-life-related situations. Little is yet known about which factors are associated with death literacy. A cross-sectional survey using the Swedish version of the Death Literacy Index, the DLI-S, was therefore conducted to explore associations between death literacy and sociodemographic, health, and experience variables., Methods: A quota sample of 503 adults (mean age 49.95 ± 17.92), recruited from an online Swedish survey panel, completed a survey comprising the DLI-S and background questions., Results: A hierarchical regression model with 3 blocks explained 40.5% of the variance in death literacy, F (22, 477) = 14.75. The sociodemographic factors age, gender, education, widowhood, and religious/spiritual belief accounted for 13.7% of the variance. Adding professional care factors contributed to an additional 15.8% of variance, with working in health care being significantly associated with death literacy. Including experiential factors explained another 11.0% of the variance, of which experiences of caring for and supporting dying and grieving people, both in a work, volunteer, or personal context, were positively associated with death literacy., Significance of Results: This study contributes a tentative explanatory model of the influence of different factors on death literacy, outlining both direct and indirect associations. Our findings also support the hypothesized experiential basis for death literacy development in the Swedish context. The moderate degree of overall variance explained suggests there may be additional factors to consider to better understand the death literacy construct and how its development may be supported.

Competing Interests: Competing interests: None declared.

Background: Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear., Methods: We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models., Results: During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44-4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86-1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66-2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05-3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25-3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05-1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02-1.32])., Conclusions: Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.

Background: Proactive conversations about individual preferences between residents, relatives, and staff can support person-centred, value-concordant end-of-life (EOL) care. Nevertheless, prevalence of such conversations is still low in residential care homes (RCHs), often relating to staff's perceived lack of skills and confidence. Using tools may help staff to facilitate EOL conversations. While many EOL-specific tools are script-based and focus on identifying and documenting treatment priorities, the DöBra card tool is developed to stimulate reflection and conversation about EOL care values and preferences. In this study, we explore staff's experiences of use, usability, and perceived impact of the DöBra cards in supporting discussion about EOL care in RCH settings., Methods: This qualitative study was based on data from two participatory action research processes in which RCH staff tested and evaluated use of DöBra cards in EOL conversations. Data comprise 6 interviews and 8 group meetings with a total of 13 participants from 7 facilities. Qualitative content analysis was performed to identify key concepts in relation to use, usability, and impact of the DöBra cards in RCH practice., Results: Based on participants' experiences of using the DöBra cards as an EOL conversation tool in RCHs, we identified three main categories in relation to its usefulness. Outcomes of using the cards (1) included the outlining of content of conversations and supporting connection and development of rapport. Perceived impact (2) related to enabling openings for future communication and aligning care goals between stakeholders. Use and usability of the cards (3) were influenced by supporting and limiting factors on the personal and contextual level., Conclusions: This study demonstrates how the DöBra cards was found to be useful by staff for facilitating conversations about EOL values, influencing both the content of discussion and interactions between those present. The tool encouraged reflection and interaction, which staff perceived as potentially helpful in building preparedness for future care-decision making. The combination of providing a shared framework and being adaptable in use appeared to be key features for the DöBra cards usability in the RCH setting., (© 2022. The Author(s).)

About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksät and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time ≥5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping and p value thresholding was robustly associated with disorder severity (β PGS  = 1.30; 95% CI: 0.72, 1.88; p = 1.2 × 10 -5 ) across all p value thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders., (© 2022. The Author(s).)

The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between ABO blood groups and diseases risk. Here, we sought to test for association between ABO genotypes (OO, OA, AA; OB, BB, and AB) and a large set of common inflammatory and cardiovascular diseases in UK Biobank as well as disease-related protein biomarkers in NSPHS. We first tested for association by conducting a likelihood ratio test, testing whether ABO contributed significantly to the risk for 24 diseases, and 438 plasma proteins. For phenotypes with FDR < 0.05, we tested for pair-wise differences between genetically determined ABO genotypes using logistic or linear regression. Our study confirmed previous findings of a strong association between ABO and cardiovascular disease, identified associations for both type 1 and type 2 diabetes, and provide additional evidence of significant differences between heterozygous and homozygous allele carriers for pulmonary embolism, deep vein thrombosis, but also for von Willebrand factor levels. Furthermore, the results indicated an additive effect between genotypes, even between the two most common A subgroups, A1 and A2. Additionally, we found that ABO contributed significantly to 39 plasma proteins, of which 23 have never been linked to the ABO locus before. These results show the need of incorporating ABO genotype information in the consultation and management of patients at risk, rather than classifying patients into blood groups., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Conversations about values for the end-of-life (EoL) between residents, relatives, and staff may allow EoL preparation and enable value-concordant care, but remain rare in residential care home (RCH) practice. In this article, longitudinal qualitative analysis was used to explore changes in staff discussions about EoL conversations throughout workshop series based on reflection and knowledge exchange to promote EoL communication in RCHs. We identified three overall continuums of change: EoL conversations became perceived as more feasible and valuable; conceptualizations of quality EoL care shifted from being generalizable to acknowledging individual variation; and staff's role in facilitating EoL communication as a prerequisite for care decision-making was emphasized. Two mechanisms influenced changes: cognitively and emotionally approaching one's own mortality and shifting perspectives of EoL care. This study adds nuance and details about changes in staff reasoning, and the mechanisms that underlie them, which are important aspects to consider in future EoL competence-building initiatives.

Objectives: Bleeding is the most common non-ischemic complication in patients with coronary revascularisation procedures, associated with prolonged hospitalisation and increased mortality. Many factors predispose for bleeds in these patients, among those sex. Anyhow, few studies have characterised the population receiving triple antithrombotic therapy (TAT) as well as long term bleeds from a sex perspective. We investigated the one year rate of bleeds in patients receiving TAT, potential sex disparities and premature discontinuation of TAT. We also assessed health care costs in bleeders vs non-bleeders., Setting: Three hospitals in the County of Östergötland, Sweden during 2009-2015., Participants: All patients discharged with TAT registered in the SWEDEHEART registry., Primary and Secondary Outcome Measures: All bleeds receiving medical attention during one-year follow-up were collected by retrieving relevant information about each patient from medical records. Resource use associated with bleeds was assigned unit cost to estimate the health care costs associated with bleeding episodes., Results: Among 272 patients, 156 bleeds occurred post-discharge, of which 28.8% were gastrointestinal. In total 54.4% had at least one bleed during or after the index event and 40.1% bled post discharge of whom 28.7% experienced a TIMI major or minor bleeding. Women discontinued TAT prematurely more often than men (52.9 vs 36.1%, p = 0.01) and bled more (48.6 vs. 37.1%, p = 0.09). One-year mean health care costs were EUR 575 and EUR 5787 in non-bleeding and bleeding patients, respectively., Conclusion: The high bleeding incidence in patients with TAT, especially in women, is a cause of concern. There is a need for an adequately sized randomised, controlled trial to determine a safe but still effective treatment for these patients., Competing Interests: The authors have declared that no competing interests exist.

Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose of this study is to clarify the time-dependent effects between long-term oral contraceptive use and cancer risk. We performed an observational study in 256,661 women from UK Biobank, born between 1939 and 1970. Information on cancer diagnoses were collected from self-reported data and from national registers until March 2019. Cumulative risk of cancer over the timespan of the study, as measured by the OR, and instantaneous risk, as measured by the HR, were assessed using Logistic and Cox regression analyses, respectively. The odds were lower among ever users, compared with never users, for ovarian cancer [OR = 0.72; 95% confidence interval (CI), 0.65-0.81] and endometrial cancer (OR = 0.68; 95% CI, 0.62-0.75), an association that was stronger with longer use ( P < 0.001). Increased odds were seen for breast cancer in women when limiting the follow-up to 55 years of age (OR = 1.10; 95% CI, 1.03-1.17), but not for the full timespan. We only found a higher HR for breast cancer in former users immediately (≤2 years) after discontinued oral contraceptive use (HR = 1.55; 95% CI, 1.06-2.28), whereas the protective association for ovarian and endometrial cancer remained significant up to 35 years after last use of oral contraceptives. Given the body of evidence presented in our study, we argue that oral contraceptives can dramatically reduce women's risk of ovarian and endometrial cancer, whereas their effect on lifetime risk of breast cancer is limited. SIGNIFICANCE: These results enable women and physicians to make more informed decisions considering oral contraceptive use, thus constituting an important step toward personalized medicine., (©2020 American Association for Cancer Research.)

Objective: It has been suggested that the mechanism behind cardiac troponin elevation after strenuous exercise is passage through a cell membrane with changed permeability rather than myocardial cell death. We hypothesised that an increase of cardiac specific myosin heavy chain-alpha (MHC-α; 224 kDa compared with cardiac troponin T's (cTnT) 37 kDa) could hardly be explained by passage through a cell membrane., Methods: Blood samples were collected from 56 athletes (15 female, age 42.5±9.7, range 24-70 years) before, directly after and on days 1-8 after an Ironman. Biomarkers (C reactive protein (CRP), cTnT, creatine kinase (CK), MHC-α, myoglobin (MG), creatinine (C) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured., Results: The course of MHC-α concentration (µg/L) was 1.33±0.53 (before), 2.57±0.78 (directly after), 1.51±0.53 (day 1), 2.74±0.55 (day 4) and 1.83±0.76 (day 6). Other biomarkers showed a one-peaked increase with maximal values either directly after the race or at day 1: cTnT 76 ± 80 ng/L (12-440; reference<15), NT-proBNP 776±684 ng/L (92-4700; ref.<300), CK 68±55 µkat/L (5-280; ref.<1.9), MG 2088±2350 µg/L (130-17 000; ref.<72) and creatinine 100±20 µmol/L (74-161; ref.<100), CRP 49±23 mg/L (15-119; ref.<5)., Conclusion: MHC-α exhibited a two-peaked increase which could represent a first release from the cytosolic pool and later from cell necrosis. This is the first investigation of MHC-α plasma concentration after exercise., Competing Interests: Competing interests: None declared.

Crambe abyssinica is a plant with potential for use in industrial (non-food) plant oil production. The side stream from this oil production is a high-protein crambe meal that has limited value, as it is not fit for food or feed use. However, it contains proteins that could potentially make it a suitable raw material for higher-value products. The purpose of this study was to find methods of making this side stream into extruded films, showing that products with a higher value can be produced. The study mainly considered the development of material compositions and methods of preparing and extruding the material. Wheat gluten was added as a supportive protein matrix material, together with glycerol as a plasticizer and urea as a denaturant. The extrudate was evaluated with respect to mechanical (tensile testing) and oxygen barrier properties, and the extrudate structure was revealed visually and by scanning electron microscopy. A denser, more homogeneous material had a lower oxygen transmission rate, higher strength, and higher extensibility. The most homogeneous films were made at an extruder die temperature of 125-130 °C. It is shown here that a film can be extruded with promising mechanical and oxygen barrier properties, the latter especially after a final compression molding step.

Background. Foraging efficiency is critical in determining the success of organisms and may be affected by a range of factors, including resource distance and quality. For social insects such as ants, outcomes must be considered at the level of both the individual and the colony. It is important to understand whether anthropogenic disturbances, such as forestry, affect foraging loads, independent of effects on the quality and distribution of resources. We asked if ants harvest greater loads from more distant and higher quality resources, how individual efforts scale to the colony level, and whether worker loads are affected by stand age. Methods. First, we performed a fine-scale study examining the effect of distance and resource quality (tree diameter and species) on harvesting of honeydew by red wood ants, Formica aquilonia, in terms of crop load per worker ant and numbers of workers walking up and down each tree (ant activity) (study 1). Second, we modelled what the combination of load and worker number responses meant for colony-level foraging loads. Third, at a larger scale, we asked whether the relationship between worker load and resource quality and distance depended on stand age (study 2). Results. Study 1 revealed that seventy percent of ants descending trees carried honeydew, and the percentage of workers that were honeydew harvesters was not related to tree species or diameter, but increased weakly with distance. Distance positively affected load mass in both studies 1 and 2, while diameter had weak negative effects on load. Relationships between load and distance and diameter did not differ among stands of different ages. Our model showed that colony-level loads declined much more rapidly with distance for small diameter than large diameter trees. Discussion. We suggest that a negative relationship between diameter and honeydew load detected in study 1 might be a result of crowding on large diameter trees close to nests, while the increase in honeydew load with distance may result from resource depletion close to nests. At the colony level, our model suggests that very little honeydew was harvested from more distant trees if they were small, but that more distant larger trees continued to contribute substantially to colony harvest. Although forestry alters the activity and foraging success of red wood ants, study 2 showed that it does not alter the fundamental rules determining the allocation of foraging effort.

Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

Assessing ecological sustainability involves monitoring of indicators and comparison of their states with performance targets that are deemed sustainable. First, a normative model was developed centered on evidence-based knowledge about (a) forest composition, structure, and function at multiple scales, and (b) performance targets derived by quantifying the habitat amount in naturally dynamic forests, and as required for presence of populations of specialized focal species. Second, we compared the Forest Stewardship Council (FSC) certification standards' ecological indicators from 1998 and 2010 in Sweden to the normative model using a Specific, Measurable, Accurate, Realistic, and Timebound (SMART) indicator approach. Indicator variables and targets for riparian and aquatic ecosystems were clearly under-represented compared to terrestrial ones. FSC's ecological indicators expanded over time from composition and structure towards function, and from finer to coarser spatial scales. However, SMART indicators were few. Moreover, they poorly reflected quantitative evidence-based knowledge, a consequence of the fact that forest certification mirrors the outcome of a complex social negotiation process.

Restoration of habitats is critically important in preventing full realization of the extinction debt owed as a result of anthropogenic habitat destruction. Although much emphasis has been placed on macrohabitats, suitable microhabitats are also vital for the survival of most species. The aim of this large-scale field experiment was to evaluate the relative importance of manipulated microhabitats, i.e., dead wood substrates of spruce (snags, and logs that were burned, inoculated with wood fungi or shaded) and macrohabitats, i.e., stand types (clear-cuts, mature managed forests, and forest reserves) for species richness, abundance and assemblage composition of all saproxylic and red-listed saproxylic beetles. Beetles were collected in emergence traps in 30 forest stands in 2001, 2003, 2004 and 2006. More individuals emerged from snags and untreated logs than from burned and shaded logs, but species richness did not differ among substrates. Assemblage composition differed among substrates for both all saproxylics and red-listed saproxylic species, mainly attributed to different assemblage composition on snags. This suggests that the practise of leaving snags for conservation purposes should be complemented with log supplementation. Clear-cuts supported fewer species and different assemblages from mature managed forests and reserves. Neither abundance, nor species richness or assemblage composition differed between reserves and mature managed forests. This suggests that managed stands subjected to selective cutting, not clear-felling, maintain sufficient old growth characteristics and continuity to maintain more or less intact assemblages of saproxylic beetles. Thus, alternative management methods, e.g., continuity forestry should be considered for some of these stands to maintain continuity and conservation values. Furthermore, the significantly higher estimated abundance per ha of red-listed beetles in reserves underlines the importance of reserves for maintaining viable populations of rare red-listed species and as source areas for saproxylic species in boreal forest landscapes.

Forest management alters species behaviours, distributions and interactions. To evaluate forestry effects on ant foraging performance, we compared the quality and quantity of honeydew harvested by ants among clear-cuts, middle-aged and mature spruce-dominated stands in boreal forests in Sweden. Honeydew quality was examined using honeydew collected by squeezing the gasters of laden Formica aquilonia workers. We used fifteen laden individuals at each study site (four replicates of each stand age) and analysed honeydew chemical composition with gas chromatography-mass spectroscopy. To compare the quantity of honeydew collected by individual ants, we collected and weighed five ants moving up and five ants moving down each of ten trees at the twelve sites (totally 1200 ants). The concentration of trehalose in honeydew was lower in clear-cuts compared with middle aged and mature stands, and similar trends were shown for sucrose, raffinose and melezitose, indicating poorer honeydew quality on clear cuts. Concentrations of the amino acid serine were higher on clear-cuts. The same trend occurred for glutamine, suggesting that increased N-uptake by the trees after clear cutting is reflected in the honeydew of aphids. Ants in mature stands had larger heads and carried proportionally more honeydew and may therefore be more efficient foragers. Human alternation of habitats through clear-cutting thus affects food quality and worker condition in F. aquilonia. This is the first study to show that honeydew quality is affected by anthropogenic disturbances, likely contributing to the reduction in size and abundance of F. aquilonia workers and mounds after clear cutting.

1. There has been considerable debate on the importance of competition in ecological communities, but its importance in structuring ant assemblages has often been uncritically accepted. Here, we briefly review field experiments examining competition in ant assemblages and use a removal experiment to test the effect of the classical territorial dominant ant, Formica aquilonia. Ants of this species group are thought to structure communities through a dominance hierarchy. 2. First, we used pitfall traps to compare the abundance of other ants in replicated sites with low and high densities of F. aquilonia. We found differences in community composition, in particular, Camponotus herculeanus was more common in low-density sites, in accordance with predictions. Differences in ant assemblages were not owing to differences in measured habitat variables. 3. We removed F. aquilonia from a set of high-density sites, using physical and chemical methods, and repeated these procedures at procedural control sites. One year after removal, abundances of F. aquilonia at removal sites were similar to those at low-density sites. However, the composition of other species did not change in response to F. aquilonia removal. Replication rates were identical in the mensurative and experimental components of this study, so this is unlikely to be owing to the analysis being insufficiently powerful. 4. We suggest three possibilities for the lack of difference. First, the study may have been too short term or small scale to detect differences. However, previous studies have shown effects on smaller spatial- and temporal-scales. Second, priority effects may be important in the successful colonisation by F. aquilonia. Thirdly, boreal ant assemblages may be too depauperate for redundancy in ecological roles and for competition to play an important structuring role. 5. We thus recommend that long-term large-scale experiments be considered essential if we are to distinguish between competing hypotheses in community ecology., (© 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.)

Melanophores are pigmented cells in lower vertebrates capable of quick color changes and thereby suitable as whole cell biosensors. In the frog dermis skin layer, the large and dark pigmented melanophore surrounds a core of other pigmented cells. Upon hormonal stimulation the black-brown pigment organelles will redistribute within the melanophore, and thereby cover or uncover the core, making complex color changes possible in the dermis. Previously, melanophores have only been cultured on flat surfaces. Here we mimic the three dimensional biological geometry in the frog dermis by culturing melanophores on fluorescent plastic microbeads. To demonstrate biosensing we use the hormones melatonin and alpha-melanocyte stimulating hormone (alpha-MSH) as lightening or darkening stimuli, respectively. Cellular responses were successfully demonstrated on single cell level by fluorescence microscopy, and in cell suspension by a fluorescence microplate reader and a previously demonstrated computer screen photo-assisted technique. The demonstrated principle is the first step towards "single well/multiple read-out" biosensor arrays based on suspensions of different selective-responding melanophores, each cultured on microbeads with distinctive spectral characteristics. By applying small amount of a clinical sample, or a candidate substance in early drug screening, to a single well containing combinations of melanophores on beads, multiple parameter read-outs will be possible.