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Introduction: The gerontological literature suggests that external housing-related control beliefs (HCB) influence activities of daily living (ADL) among older people, but knowledge is scarce for people with Parkinson’s disease (PD). This longitudinal study aimed to explore the directions of the relationship between external HCB and ADL among people with PD. Methods: Baseline (T1) and 3-year follow-up data (T2) were collected from 154 people with PD (mean age = 68 years, T1). Two regression analyses were applied, where dependent (T2 values) and independent (T1 values) variables—external HCB score and PD specific ADL (PADLS)—were switched, adjusting for age, disease severity, cognitive functioning, and accessibility problems. Results: There was a significant effect of ADL on external HCB (β = 3.07, p

Abstract Background Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population. Methods All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT. Results In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81–9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT. Conclusions SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.

Expert performance is associated with practice, partly because of causal effects of practice on skill (i.e., learning). However, the practice-expertise association is also influenced by a complex interplay between genes and environment including partly overlapping genetic influences. The importance of cognitive ability in the practice-expertise association is less well understood. Therefore, we first examined whether genetic predisposition for cognitive performance, operationalized as a polygenic score, is associated with music practice and expertise. Next, we tested whether there is evidence for gene × environment interaction, i.e., whether effects of practice on expertise differ depending on an individual's genetic predisposition for cognitive performance. Polygenic scores for cognitive performance (PGScp) and multi-trait cognitive performances, including educational attainment and mathematical performances (PGScps) were calculated for approximately 3800 genotyped Swedish individuals with information available on their cumulative amount of music practice, musical achievement, and musical auditory discrimination. We found that higher PGScp and PGScps were associated with higher levels of achievement, musical auditory discrimination, and more practice, although the association with practice weakened when controlling for education. Music practice was linked to both expertise outcomes, and the effect sizes of these associations varied depending on an individual's PGScp and PGScps (with the exception of PGScp for musical auditory discrimination). These results suggest genetic pleiotropy between cognitive performance and musical expertise. Additionally, they reveal the presence of G × E interaction in skill acquisition, as effects of practice on musical expertise are stronger for individuals with a higher genetic predisposition for cognitive performance.

Abstract Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.

Abstract Music production is a universal phenomenon reaching far back into our past. Given its ubiquity, evolution theorists have postulated adaptive functions for music, such as strengthening in-group cohesion, intimidating enemies, or promoting child bonding. Here, we focus on a longstanding Darwinian hypothesis, suggesting that music production evolved as a vehicle to display an individual’s biological fitness in courtship competition, thus rendering musicality a sexually selected trait. We also extend this idea to visual artists. In our design, we employed different versions of naturalistic portraits that manipulated the presence or absence of visual cues suggesting that the person was an artist or a non-artist (e.g., farmer, teacher, physician). Participants rated each portrayed person’s appeal on multiple scales, including attractiveness, interestingness, sympathy, and trustworthiness. Difference scores between portrait versions revealed the impact of the artistic/non-artistic visual cues. We thus tested Darwin’s hypothesis on both a within-subject and within-stimulus level. In addition to this implicit approach, we collected explicit ratings on the appeal of artists versus non-artists. The results demonstrate divergent findings for both types of data, with only the explicit statements corroborating Darwin’s hypothesis. We discuss this divergence in detail, along with the particular role of interestingness revealed by the implicit data.

The deliberate practice (DP) theory claims that expertise essentially reflects the accumulated amount of deliberate practice, and that with sufficient practice, genetic influences on expertise will be bypassed. Thus, a core prediction of the DP theory is that genetic effects on performance decrease as a function of practice. Here, we test this prediction using music as a model domain. Musical expertise (measured with a musical auditory discrimination test) and lifetime practice hours were determined in 6471 twins including 1302 complete twin pairs. We fitted a bivariate Cholesky decomposition with practice hours as a moderator to determine to what extent genetic and environmental influences on musical expertise are influenced by practice hours. On average, 50% of individual differences in musical expertise were due to genetic influences, whereas shared environmental and residual influences each explained about 25%. Importantly, music practice significantly moderated these estimates. Variation in musical expertise decreased with more practice hours due to decreased shared environmental and residual variance. In contrast, the overall genetic component was unaffected by the number of practice hours. Consequently, the relative genetic contribution (heritability) increased with more practice hours. These findings are in contrast with predictions from the DP theory and suggest that genetic predisposition remains important for musical expertise even after prolonged practice.

Abstract Background Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA. Methods This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Results Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance. Conclusions In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue. Trial registration ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.

Abstract While music engagement is often regarded as beneficial for mental health, some studies report higher risk for depression and anxiety among musicians. This study investigates whether shared underlying genetic influences (genetic pleiotropy) or gene-environment interaction could be at play in the music-mental health association using measured genotypes. In 5,648 Swedish twins with information on music and sport engagement, creative achievements, self-reported mental health and psychiatric diagnoses based on nationwide patient registries, we derived polygenic scores for major depression, bipolar disorder, schizophrenia, neuroticism, sensitivity to environmental stress, depressive symptoms and general musicality. In line with phenotypic associations, individuals with higher polygenic scores for major depression and bipolar disorder were more likely to play music, practice more music and reach higher levels of general artistic achievements, while a higher genetic propensity for general musicality was marginally associated with a higher risk for a depression diagnosis. Importantly, polygenic scores for major depression and bipolar remained associated with music engagement when excluding individuals who experienced psychiatric symptoms, just as a genetic propensity for general musicality predicted a depression diagnosis regardless of whether and how much individuals played music. In addition, we found no evidence for gene-environment interaction: the phenotypic association between music engagement and mental health outcomes did not differ for individuals with different genetic vulnerability for mental health problems. Altogether, our findings suggest that mental health problems observed in musically active individuals are partly explained by a pre-existing genetic risk for depression and bipolar disorder and likely reflect horizontal pleiotropy (when one gene influences multiple traits), rather than causal influences of mental health on music engagement, or vice versa (referred to as vertical pleiotropy).

Abstract Background Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2×2×2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest. Methods By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all-cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors ≤ 5% and the risk of type-2 errors ≤ 10%, we will quantify the maximum interaction effect we can accept if the planned sample size is increased by 5% to take into account possible interaction between the trial interventions. Secondly, we will assess how interaction effects influence the minimal detectable difference we may confirm or reject to take into account 5% (small interaction effect), 10% (moderate), or 15% (large) positive interactions in simulations with no ‘true’ intervention effect (type-1 errors) and small (5%), moderate (10%), or large negative interactions (15%) in simulations with ‘true’ intervention effects (type-2 errors). Moreover, we will investigate how much the sample size must be increased to account for a small, moderate, or large interaction effects. Discussion This protocol for a simulation study will inform the design of a 2×2×2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results. Trial registration Not relevant

The prognosis of metastatic urothelial carcinoma (mUC) patients is poor, and early prediction of systemic therapy response would be valuable to improve outcome. In this exploratory study, we investigated protein profiles in sequential plasma‐isolated extracellular vesicles (EVs) from a subset of mUC patients treated within a Phase I trial with vinflunine combined with sorafenib. The isolated EVs were of exosome size and expressed exosome markers CD9, TSG101 and SYND‐1. We found, no association between EVs/ml plasma at baseline and progression‐free survival (PFS). Protein profiling of EVs, using an antibody‐based 92‐plex Proximity Extension Assay on the Oncology II® platform, revealed a heterogeneous protein expression pattern. Qlucore bioinformatic analyses put forward a protein signature comprising of SYND‐1, TNFSF13, FGF‐BP1, TFPI‐2, GZMH, ABL1 and ERBB3 to be putatively associated with PFS. Similarly, a protein signature from EVs that related to best treatment response was found, which included FR‐alpha, TLR 3, TRAIL and FASLG. Several of the markers in the PFS or best treatment response signatures were also identified by a machine learning classification algorithm. In conclusion, protein profiling of EVs isolated from plasma of mUC patients shows a potential to identify protein signatures that may associate with PFS and/or treatment response.

Abstract To further our understanding of the genetics of musicality, we explored associations between a polygenic score for self-reported beat synchronization ability (PGSrhythm) and objectively measured rhythm discrimination, as well as other validated music skills and music-related traits. Using family data, we were able to further explore potential pathways of direct genetic, indirect genetic (through passive gene–environment correlation) and confounding effects (such as population structure and assortative mating). In 5648 Swedish twins, we found PGSrhythm to predict not only rhythm discrimination, but also melody and pitch discrimination (betas between 0.11 and 0.16, p

Abstract Background Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016.

Abstract Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006–2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1–2) versus poor (CPC 3–5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46–0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome.

Introduction: The gerontological literature suggests that external housing-related control beliefs (HCB) influence activities of daily living (ADL) among older people, but knowledge is scarce for people with Parkinson's disease (PD). This longitudinal study aimed to explore the directions of the relationship between external HCB and ADL among people with PD. Methods: Baseline (T1) and 3-year follow-up data (T2) were collected from 154 people with PD (mean age = 68 years, T1). Two regression analyses were applied, where dependent (T2 values) and independent (T1 values) variables—external HCB score and PD specific ADL (PADLS)—were switched, adjusting for age, disease severity, cognitive functioning, and accessibility problems. Results: There was a significant effect of ADL on external HCB (β = 3.07, p <.001, CI [1.28, 4.85]), but no effect in the reverse direction. The proportion with moderate-extreme ADL difficulties increased over time (from 20.8% to 32.5%, p =.006). Discussion: ADL difficulties seem to lead to higher external HCB, but not the other way around, which contradicts assumptions in environmental gerontology theories. This new knowledge can promote theory development. While additional studies are required to verify whether this is a disease-specific finding, this indicates the importance of targeting ADL if the purpose is to influence external HCB among people with PD. [ABSTRACT FROM AUTHOR]