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Sickness absence from work has a large adverse impact on both individuals and societies in Sweden and the costs for sickness absence were calculated to 64.6 billion Swedish kronor (approx. 5.6 billion in Euros) in 2020. Although high cardiorespiratory fitness may protect against potential adverse effects of high physical workload, research on the moderating effect of respiratory fitness in the relation between having an occupation with high physical workload and sickness absence is scarce. To study the moderating effect of cardiorespiratory fitness in the association between occupation and psychiatric, musculoskeletal, and cardiorespiratory diagnoses. Data was retrieved from the HPI Health Profile Institute database (1988–2020) and Included 77,366 participants (mean age 41.8 years, 52.5% women) from the Swedish workforce. The sample was chosen based on occupational groups with a generally low education level and differences in physical workload. Hurdle models were used to account for incident sickness absence and the rate of sickness absence days. There were differences in sickness absence between occupational groups for musculoskeletal and cardiorespiratory diagnoses, but not for psychiatric diagnoses. In general, the association between occupation and musculoskeletal and cardiorespiratory diagnoses was moderated by cardiorespiratory fitness in most occupational groups with higher physical workload, whereas no moderating effect was observed for psychiatric diagnoses. The study results encourage community and workplace interventions to both consider variation in physical workload and to maintain and/or improve cardiorespiratory fitness for a lower risk of sickness absence, especially in occupations with high physical workload. [ABSTRACT FROM AUTHOR]

Summary: Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh‐worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold‐standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh‐worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single‐night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh‐worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free‐living settings. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have fundamentally improved survival from advanced cutaneous melanoma. Significant efforts have been made to understand the ICI response to identify ways to further improve outcomes. One such approach has been to investigate gene expression associated with response to ICI, which has identified various immune‐related mRNA signatures, including a six‐gene IFN‐γ signature (IFN‐γ6), an expanded immune signature (IFN‐γ18), an effector T‐cell gene signature (Teff), and a Teff‐associated and IFN‐γ‐associated gene signature (Teff + IFN‐γ). Given that these signatures appear to reflect expression from T cells and the level of tumour‐infiltrating immune cells has been associated with survival, we hypothesised that the prognostic value of the signatures is not limited to ICI treatment and investigated if they were associated with survival also in patients who never received ICI. The signatures were not present in melanoma cell lines when compared with tumour samples, confirming that the signatures were likely derived from the samples' non‐tumour (immune) components. We acquired expression and survival data from five melanoma cohorts with a wide range of disease stages, treatments and metrics for survival, and correlated the expression signatures with survival. All four signatures were significantly associated (p <.05) with survival in four of five cohorts, with hazard ratios ranging from 0.69 to 0.92. We conclude that these immune signatures' association with survival is not specific to ICI‐treated patients, but present in a number of settings. [ABSTRACT FROM AUTHOR]

Purpose: Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Methods: Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. Results: In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (β = 0.74; p < 0.001) and myocardium (β = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Conclusion: Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) tumors arise on the palms, soles, fingers, toes, and nailbeds. A comprehensive systematic meta‐analysis of AM genomic aberrations has not been conducted to date. A literature review was carried out to identify studies sequencing AM. Whole‐genome/exome data from 181 samples were identified. Targeted panel sequencing data from MSK‐IMPACT were included as a validation cohort (n = 92), and studies using targeted hot spot sequencing were also collated for BRAF (n = 26 studies), NRAS (n = 21), and KIT (n = 32). Statistical analysis indicated BRAF, NRAS, PTEN, TYRP1, and KIT as significantly mutated genes. Frequent copy‐number aberrations were also found for important cancer genes, such as CDKN2A, KIT, MDM2, CCND1, CDK4, and PAK1, among others. Mapping genomic alterations within the context of the hallmarks of cancer identified four components frequently altered, including (i) sustained proliferative signaling and (ii) evading growth suppression, (iii) genome instability and mutation, and (iv) enabling replicative immortality. This analysis provides the largest analysis of genomic aberrations in AM in the literature to date and highlights pathways that may be therapeutically targetable. [ABSTRACT FROM AUTHOR]

In this study of the 'Resolving supermAssive Black hole Binaries In galacTic hydrodynamical Simulations' (RABBITS) series, we investigate the orbital evolution of supermassive black holes (SMBHs) during galaxy mergers. We simulate both disc and elliptical galaxy mergers using the ketju code, which can simultaneously follow galaxy (hydro-)dynamics and small-scale SMBH dynamics with post-Newtonian corrections. With our SMBH binary subgrid model, we show how active galactic nuclei (AGNs) feedback affects galaxy properties and SMBH coalescence. We find that simulations without AGN feedback exhibit excessive star formation, resulting in merger remnants that deviate from observed properties. Kinetic AGN feedback proves more effective than thermal AGN feedback in expelling gas from the centre and quenching star formation. The different central galaxy properties, which are a result of distinct AGN feedback models, lead to varying rates of SMBH orbital decay. In the dynamical friction phase, galaxies with higher star formation and higher SMBH masses possess denser centres, become more resistant to tidal stripping, experience greater dynamical friction, and consequently form SMBH binaries earlier. As AGN feedback reduces gas densities in the centres, dynamical friction by stars dominates over gas. In the SMBH hardening phase, compared to elliptical mergers, disc mergers exhibit higher central densities of newly formed stars, resulting in accelerated SMBH hardening and shorter merger time-scales (i.e. |$\lesssim 500$| Myr versus |$\gtrsim 1$| Gyr). Our findings highlight the importance of AGN feedback and its numerical implementation in understanding the SMBH coalescing process, a key focus for low-frequency gravitational wave observatories. [ABSTRACT FROM AUTHOR]

Background There is a lack of knowledge about internet-based cognitive behavioural therapy in patients with cardiovascular disease, and its effects on depressive symptoms and physical activity. Aim To examine trajectories of depressive symptoms and physical activity, and to explore if these trajectories are linked with the delivery of internet-based cognitive behavioural therapy. Methods A secondary-analysis of data collected in a randomised controlled trial that evaluated the effects of a 9-week internet-based cognitive behavioural therapy programme compared to an online discussion forum on depressive symptoms in cardiovascular disease patients. Data were collected at baseline, once weekly during the 9-week intervention period and at the 9-week follow-up. The Montgomery A° sberg depression rating scale - self-rating (MADRS-S) was used to measure depressive symptoms. Two modified items from the physical activity questionnaire measuring frequency and length of physical activity were merged to form a physical activity factor. Results After 2 weeks the internet-based cognitive behavioural therapy group had a temporary worsening in depressive symptoms. At 9-week follow-up, depressive symptoms (P < 0.001) and physical activity (P = 0.02) had improved more in the internet-based cognitive behavioural therapy group. Only in the internet-based cognitive behavioural therapy group, was a significant correlation (r = -0.39, P = 0.002) between changes in depressive symptoms and changes in physical activity found. Structural equation analyses revealed that internet-based cognitive behavioural therapy decreased depressive symptoms, and that a decrease in depression, in turn, resulted in an increase in physical activity. Conclusions Internet-based cognitive behavioural therapy was more effective than an online discussion forum to decrease depressive symptoms and increase physical activity. Importantly, a decrease in depressive symptoms needs to precede an increase in physical activity. [ABSTRACT FROM AUTHOR]

Protection of telomeres 1 (POT1) is a component of the shelterin complex of six subunits encoded by adrenocortical dysplasia protein homologue ( I ACD i ; also known as TPP1), I POT1 i , telomeric repeat binding factor 1 ( I TERF1 i ), telomeric repeat binding factor 2 ( I TERF2 i ), TERF1-interacting nuclear factor 2 ( I TINF2 i ) and TERF2 interacting protein ( I TERF2IP i ), which binds to single-stranded telomeric DNA to regulate telomere elongation and integrity.1 The telomerase and shelterin complexes play specific roles in telomere maintenance and prevention of activation of DNA damage response pathways at telomeres, by protecting single-stranded DNA (ssDNA) overhangs.1 Conserved oligonucleotide/oligosaccharide-binding (OB) domains in I POT1 i recognise specific ssDNA motifs with high affinity and are required for I POT1 i function.1 Acquired and inherited variants in I POT1 i that alter these OB folds are associated with longer telomeres due to disruption of shelterin function.2 Rare germline pathogenic variants in I POT1 i predispose to chronic leucocyte leukaemia (CLL), glioma, angiosarcoma, osteosarcoma, thyroid cancer, colorectal cancer and cutaneous melanoma (CM), collectively termed the POT1-tumour predisposition syndrome (POT1-TPDS; Fig 1). Proband II:1 was the only individual chosen for whole-genome sequencing (WGS) due to their extensive personal cancer history (MCC AUS244) to assess the burden of cancer risk alleles among individuals with multiple primary cancers. [Extracted from the article]

The risk for hip and vertebral fracture was determined in 10,752 patients diagnosed with myeloproliferative neoplasms (MPN) in Sweden 1995–2015. The mean follow-up time were 6.34 years. Five percent developed hip fracture and 1.3% a vertebral fracture. There was a significant increased risk for fracture among the MPN patients compared with the Swedish population. The ratio of observed (obs) and expected (exp) number of hip fracture in all MPN patients, polycythemia vera (PV), essential thrombocythemia and MPN undetermined (MPNu) was 1.20 (95% confidence interval (CI): 1.10–1.31), 1.37 (95% CI: 1.19–1.58), 1.02 (95% CI: 0.87–1.19), and 1.28 (95% CI: 1.07–1.52), respectively. Corresponding figures for vertebral fractures were 1.94 (95% CI: 1.64–2.29), 2.09 (95% CI: 1.56–2.75), 1.50 (95% CI: 1.06–2.07) and 2.47 (95% CI: 1.77–3.35), respectively. Patients with MPN had an increased risk of hip and vertebral fracture, especially patients with PV and MPNu in comparison with the entire Swedish population. [ABSTRACT FROM AUTHOR]

Increased bone loss has been noted in lymphoma patients; however, the incidence of hip fracture is not known. The aim of our study was to explore the risk for hip fracture in patients with lymphoma compared with the entire Swedish population. The risk of hip fracture was determined in a retrospective population cohort study of adult Swedish lymphoma patients (n = 37,236), diagnosed 1995-2015 and compared with the entire Swedish population during the same period. The incidence of hip fracture in lymphoma patients was higher in women than in men, increased by age, and decreased by calendar year as also demonstrated in the total population. 2.2% of the men and 4.7% of women with lymphoma sustained a hip fracture. For the total group of females, the hazard ratio (HR) was 1.19 (95% CI 1.11-1.28) and for men, the hazard ratio was 1.06 (95% CI 0.97-1.17) compared with the Swedish population. The HR for hip fracture (2016) was 2.80 (95% CI 1.20-6.53), 2.04 (95% CI 1.30-3.20), 1.56 (95% CI 1.21-2.01), 1.08 (95% CI 0.89-1.30), and 1.07 (95% CI 0.92-1.25) in females aged 40, 50, 60, 70, and 80 years, respectively. Corresponding figures for men were not significant in 2016. Unmarried men with lymphoma had a two times higher risk for hip fracture (HR 2.02 95% CI 1.63-2.50) compared with married men. Patients with lymphoma had an increased risk of hip fracture, especially younger women and unmarried men. The incidence of hip fracture is decreased by calendar year in the lymphoma patients and the entire Swedish population. [ABSTRACT FROM AUTHOR]

Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next‐generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four‐case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM. [ABSTRACT FROM AUTHOR]

Background: Approximately half of patients who seek care at Emergency Departments due to chest pain are diagnosed with Non-Cardiac Chest Pain (NCCP). Concerns for heart disease and misinterpretation of the symptoms increase cardiac anxiety and have a negative impact on patients' lives. Psychological interventions such as internet-delivered cognitive behavioral therapy (iCBT) are effective in treating psychological conditions such as anxiety, by helping patients to learn how to manage chest pain. Aims: To evaluate the effects of a nurse-led iCBT program on cardiac anxiety and secondary outcomes, as bodily sensations, depressive symptoms, health-related quality of life and chest pain frequency in patients with NCCP at 6- and 12-month follow-up, and to explore predictors that can have impact on the effects of the iCBT program on psychological distress. Methods: A longitudinal study of a Randomized Controlled Trial (RCT) evaluating the long-term effects of an iCBT program (n = 54) in patients with NCCP, compared to psychoeducation (n = 55). The primary outcome, cardiac anxiety was measured using the Cardiac Anxiety Questionnaire (CAQ), and the secondary outcomes were measured with The Body Sensations Questionnaire (BSQ), Patient Health Questionnaire-9 (PHQ-9), The EuroQol Visual Analog Scale (EQ-VAS) and a self-developed question to measure chest pain frequency. All measurements were performed before and after the intervention, and 3, 6 and 12 months after the intervention. Linear mixed model was used to test between-group differences in primary and secondary outcomes and multiple regression analysis was used to explore factors that may have an impact on the treatment effect of iCBT on cardiac anxiety. Results: A total of 85% (n = 93/109) participants completed the 12-month follow-up. Mixed model analysis showed no statistically significant interaction effect of time and group between the iCBT and psychoeducation groups regarding cardiac anxiety over the 12-month follow-up. However, there was a statistically significant interaction effect of time and group (p =.009) regarding chest pain frequency favouring the iCBT group. In addition, we found a group effect in health-related quality of life (p =.03) favouring the iCBT group. The regression analysis showed that higher avoidance scores at baseline were associated with improvement in cardiac anxiety at 12-month follow-up. Conclusions: Cardiac anxiety was reduced in patients with NCCP, but iCBT was not more effective than psychoeducation. Patients with a high tendency to avoid activities or situations that they believe could trigger cardiac symptoms may benefit more from psychological interventions targeting cardiac anxiety. Trial Registration: The trial was registered at ClinicalTrials.gov NCT03336112 on 08/11/2017. [ABSTRACT FROM AUTHOR]

In this study of the 'Resolving supermAssive Black hole Binaries In galacTic hydrodynamical Simulations' (RABBITS) series, we focus on the hardening and coalescing process of supermassive black hole (SMBH) binaries in galaxy mergers. For simulations including different galaxy formation processes (i.e. gas cooling, star formation, SMBH accretion, stellar, and AGN feedback), we systematically control the effect of stochastic eccentricity by fixing it to similar values during the SMBH hardening phase. We find a strong correlation between the SMBH merger time-scales and the presence of nuclear star formation. Throughout the galaxy merging process, gas condenses at the centre due to cooling and tidal torques, leading to nuclear star formation. These recently formed stars, which inherit low angular momenta from the gas, contribute to the loss cone and assist in the SMBH hardening via three-body interactions. Compared to non-radiative hydrodynamical runs, the SMBH merger time-scales measured from the runs including cooling, stellar, and SMBH physical processes tend to be shortened by a factor of ∼1.7. After fixing the eccentricity to the range of e ∼ 0.6–0.8 during the hardening phase, the simulations with AGN feedback reveal merger time-scales of ∼100–500 Myr for disc mergers and ∼1–2 Gyr for elliptical mergers. With a semi-analytical approach, we find that the torque interaction between the binary and its circumbinary disc has minimal impact on the shrinking of the binary orbit in our retrograde galaxy merger. Our results are useful in improving the modelling of SMBH merger time-scales and gravitational-wave event rates. [ABSTRACT FROM AUTHOR]

There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived 2 years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was > 20 times higher than in an aggregated population genome database (P < 5 × 10−5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy. [ABSTRACT FROM AUTHOR]

We study supermassive black hole (SMBH) binary eccentricity of equal-mass galaxy mergers in N -body simulations with the ketju code, which combines the gadget-4 fast multipole gravity solver with accurate regularized integration and post-Newtonian corrections around SMBHs. In simulations with realistic, high-eccentricity galactic merger orbits, the hard binary eccentricity is found to be a non-linear function of the deflection angle in the SMBH orbit during the final, nearly radial close encounter between the SMBHs before they form a bound binary. This mapping between the deflection angle and the binary eccentricity has no apparent resolution dependence in our simulations spanning the resolution range of 1 × 105 to 8 × 106 particles per galaxy. The mapping is also captured using a simple model with an analytical potential, indicating that it is driven by the interplay between a smooth asymmetric stellar background potential and dynamical friction acting on the SMBHs. Due to the non-linearity of this mapping, in eccentric major merger configurations, small, parsec-scale variations in the merger orbit can result in binary eccentricities varying in nearly the full possible range between e  = 0 and e  = 1. In idealized simulations, such variations are caused by finite resolution effects, and convergence of the binary eccentricity can be achieved with increasing resolution. However, in real galaxies, other mechanisms such as nuclear gas and substructure that perturb the merger orbit are likely to be significant enough for the binary eccentricity to be effectively random. Our results indicate that the distribution of these effectively random eccentricities can be studied using even moderate resolution simulations. [ABSTRACT FROM AUTHOR]

An advanced method to study geomorphology of the well-known inselberg landscape in Finnish Lapland is introduced. Conventionally topographical maps and altitude reference produced from stereographic aerial photographs has been used. Now the LiDAR data has opened a new way to study geomorphology and terrain in detail. We applied the new methods in eastern Finnish Lapland from where seven inselbergs have been identified and analysed. With an accurate elevation data and images we could identify the detailed morphology in the inselbergs and examine the processes that actively alter the terrain. LiDAR data opened a view to the preglacial history and processes. Some preliminary estimations of the rate and amount of preglacial erosion could be made. It seems that erosion rate may have been in order of 2-10 m/Myr in Lapland based on existing datings and stratigraphic observations. Weathering and erosion history in Lapland is long as the kaolinite clays of Late Cenozoic, Mesozoic or even Mesoproterozoic in age are found in the weathered bedrock. Although all disconformities older than the Mesozoic era have probably been eroded to an unidentifiable extent, there is good reason to suppose that the main characteristics of the relief, including inselbergs, originated as early as the Late Cretaceous or at least in the Palaeocene. [ABSTRACT FROM AUTHOR]

We present a high-resolution smoothed particle hydrodynamic simulation of the Antennae galaxies (NGC 4038/4039) and follow the evolution 3 Gyr beyond the final coalescence. The simulation includes metallicity-dependent cooling, star formation, and both stellar feedback and chemical enrichment. The simulated best-match Antennae reproduce well both the observed morphology and the off-nuclear starburst. We also produce for the first time a simulated two-dimensional (2D) metallicity map of the Antennae and find good agreement with the observed metallicity of off-nuclear stellar clusters; however, the nuclear metallicities are overproduced by ~0.5 dex. Using the radiative transfer code SKIRT, we produce multiwavelength observations of both the Antennae and the merger remnant. The 1-Gyr-old remnant is well fitted with a Sérsic profile of n = 7.07, and with an r-band effective radius of re = 1.6 kpc and velocity dispersion of σe = 180 km s-1 the remnant is located on the Fundamental Plane of early-type galaxies (ETGs). The initially blue Antennae remnant evolves on to the red sequence after ~2.5 Gyr of secular evolution. The remnant would be classified as a fast rotator, as the specific angular momentum evolves from λRe ≈ 0.11 to 0.14 during its evolution. The remnant shows ordered rotation and a double peaked maximum in the mean 2D line-of-sight velocity. These kinematical features are relatively common amongst local ETGs and we specifically identify three local ETGs (NGC 3226, NGC 3379, and NGC 4494) in the ATLAS3D sample, whose photometric and kinematic properties most resemble the Antennae remnant. [ABSTRACT FROM AUTHOR]

Background: While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. Methods: A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. Results: No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher overall burden of mutations in all cancer genes. Conclusions: We identified several pathogenic variants that likely predispose to at least one of the tumours in patients with multiple cancers. We additionally present evidence that there may be a higher burden of variants of unknown significance in ‘cancer genes’ in patients with multiple cancer types. Further screens of this nature need to be carried out to build evidence to show if the cancers observed in these patients form part of a cancer spectrum associated with single germline variants in these genes, whether multiple layers of susceptibility exist (oligogenic or polygenic), or if the occurrence of multiple different cancers is due to random chance. [ABSTRACT FROM AUTHOR]

Background and purpose — Slipped capital femoral epiphysis (SCFE) results in a more or less pronounced deformity of the proximal femur, sometimes causing impingement and early osteoarthritis. We studied early osteoarthritis after SCFE and the association with deformity and self-reported hip function, pain, and quality of life.Patients and methods — 9 women and 16 men, mean age 32 (21-50) years, 19 with unilateral and 6 with bilateral SCFE, participated. All patients had primarily been operated by pin or screw with no attempt at reposition of the slip. Hips were examined by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), which quantifies and locates cartilage degeneration. Plain radiographs were used to measure deformity as determined by the alpha angle. Outcome was assessed by Oxford hip score, Hip Groin Outcome score and EQ-5D-Visual scale.Results — In the 19 unilateral SCFE, on the slip side dGEMRIC mean value was 533 ms (SD 112, range 357-649) versus mean 589 ms (SD 125, range 320-788) on the non-slip side, (p = 0.01). The dGEMRIC correlated negatively to the alpha angle, correlation coefficient (CC) = -0.60, (p = 0.002). Oxford hip score, pain, and EQ-5D-Visual scale correlated to dGEMRIC CC =0.43 (p = 0.03), CC =0.40 (p = 0.05), and CC =0.49 (p = 0.01) respectively.Interpretation — After SCFE, even relatively mild residual hip deformity can be associated with cartilage degeneration. A high alpha angle was associated with worse cartilage status. The Oxford hip score identified symptoms even though our patients had not previously sought medical care after the index operation. Quality of life showed strong inverse correlation with cartilage degeneration. Objective assessment of early cartilage degeneration may be useful for treatment decisions and follow-up. [ABSTRACT FROM AUTHOR]

Traditional medicine (TM) and biomedicine represent parallel health systems in many developing countries; the latter dominating in public policies, while the former still retain considerable influence among the general public. This study investigates how mental health care professionals responsible for mental health care implementation comprehend and relate to the intersection between TM and biomedicine in the cases of Rwanda and the Eastern Cape Province, South Africa. The material is based on semi-structured interviews with mental health care stakeholders in Eastern Cape, South Africa and Rwanda. The findings confirm an impact of TM in the treatment of mental health issues in Rwanda and South Africa due to TM being more accessible than biomedical medicine, widespread traditional perceptions of mental illness in society, and the lack of knowledge of biomedical treatments. Furthermore, the respondents identified three strategies to manage the impact of TM; improved accessibility of biomedical facilities, outreach education about mental illness, and, in the Eastern Cape case, collaboration between traditional healers and biomedicine. The study points to the necessity to take TM into consideration as an important component of health systems and policies in the Global south. [ABSTRACT FROM PUBLISHER]

Technology advancements for mixed culture polyhydroxyalkanoate production have been made in recent years at pilot scale, and efforts continue towards implementation of the first commercial scale production facilities. The purpose of the present work was to develop thermogravimetric analysis (TGA) methods for routine monitoring of polymer quantity and quality in PHA-rich activated sludge biomass, and for the recovered polymers. TGA quantification of the biomass PHA content correlated directly with the maximum extractable polymer (±2% gPHA/gTS). Acid pre-treatment of the biomass, prior to sample drying, significantly increased the polymer thermal stability in the biomass. This increase helps to improve the resolution of the PHA fraction of the biomass by TGA. From the TGA results, an extension to common solids analysis from Standard Methods, by including an intermediate volatile solids (IVS) assessment, was developed to quantify biomass PHA content. The IVS method entails sample volatilization and weight loss evaluation at a selected temperature between 200 and 300 °C. This intermediate temperature is in between the Standard Method sample drying (103 °C), and ashing (550 °C) oven incubations, for relative weight loss measurements that are made routinely for solids analysis. Thermogravimetric analyses were applied in isothermal polymer recovery experiments using either acetone or 2-butanol as extraction solvents. Trends in extractability as a function of extraction temperature and time correlated directly to the poly(3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV) co-polymer composition in the biomass, over a 3-hydroxyvalerate in PHBV content ranging from 0 to 40 average weight percent, and a polymer weight average molecular mass between 200 and 600 kDa. Polymer type can be used to anticipate the extraction behavior, or conversely, as shown in the present work, isothermal polymer extraction trends can be used to infer the type of polymer present in the biomass. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between depressive symptoms, sleep disturbances, daytime sleepiness, and health-related quality of life (HRQOL) in patients with chronic heart failure (CHF).

The article discusses the association between heart failure and depression, the consequences of depression on patients with heart failure, and the factors that predispose patients with heart failure to develop or suffer from depression.

We present the new public version of the ketju supermassive black hole (SMBH) dynamics module, as implemented into gadget-4. ketju adds a small region around each SMBH where the dynamics of the SMBHs and stellar particles are integrated using an algorithmically regularized integrator instead of the leapfrog integrator with gravitational softening used by gadget-4. This enables modelling SMBHs as point particles even during close interactions with stellar particles or other SMBHs, effectively removing the spatial resolution limitation caused by gravitational softening. ketju also includes post-Newtonian (PN) corrections, which allows following the dynamics of SMBH binaries to sub-parsec scales and down to tens of Schwarzschild radii. Systems with multiple SMBHs are also supported, with the code also including the leading non-linear cross terms that appear in the PN equations for such systems. We present tests of the code showing that it correctly captures, at sufficient mass resolution, the sinking driven by dynamical friction and binary hardening driven by stellar scattering. We also present an example application demonstrating how the code can be applied to study the dynamics of SMBHs in mergers of multiple galaxies and the effect they have on the properties of the surrounding galaxy. We expect that the presented ketju SMBH dynamics module can also be straightforwardly incorporated into other codes similar to gadget-4 , which would allow coupling small-scale SMBH dynamics to the rich variety of galactic physics models that exist in the literature. [ABSTRACT FROM AUTHOR]

Background: Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods: 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings: After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion: Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed. [ABSTRACT FROM AUTHOR]

Background Heart failure (HF) is a life-threatening condition and optimal handling is necessary to reduce risk of therapy failure. The impact of the duration of HF diagnosis on HF outcome has not previously been examined. The objectives of this study were (I) to evaluate the impact of patient age on clinical outcomes, (II) to evaluate the impact of duration of the HF disease on outcomes, and (III) to evaluate the impact of age and HF duration on B-type Natriuretic Peptide (BNP) concentration in a population of HF patients. Methods and results In the UPSTEP (Use of PeptideS in Tailoring hEart failure Project) study we retrospectively evaluated how age and HF duration affected HF outcome. HF duration was divided into < 1 year, 1–5 years and > 5 years. A multivariate Cox proportional hazard regression analysis showed that HF duration influenced outcome more than age, even when adjusted for comorbidities(< 1 year versus > 5 years: HR 1.65; 95% CI 1.28–2.14; P < 0.0002) on HF mortality and hospitalisations. The influence of age on BNP showed increased BNP as age increased. However, there was a significant effect on BNP concentration when comparing HF duration of less than one year to HF duration to more than five years, even when adjusted for age. Conclusions Patients with longer HF duration had significantly worse outcome compared to those with short HF duration, even when adjusted for patient age and comorbidities. Age did not influence outcome but had an impact on BNP concentration; however, BNP concentration increased as HF duration increased. [ABSTRACT FROM AUTHOR]

Background: Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods: Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)–plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings: On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Conclusions: Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing of matched germline and tumour pairs in a well-characterized cohort of melanoma patients allowed investigation of associations between melanoma body site, age at melanoma onset and MC1R variant status with overall mutation burden and specific base pair changes observed in the corresponding melanoma. We observed statistically significant associations between mutation burden in melanoma and body site, age at onset and MC1R genotype, for both ultraviolet radiation ( UVR) signature changes (C>T and CC> TT) and non- UVR base pair substitutions, as well as with overall variant load. [ABSTRACT FROM AUTHOR]

A nearby source of Lyman-Werner (LW) photons is thought to be a central component in dissociating H2 and allowing for the formation of a direct collapse black hole seed. Nearby sources are also expected to produce copious amounts of hydrogen ionizing photons and X-ray photons. We study here the feedback effects of the X-ray photons by including a spectrum due to high-mass X-ray binaries on top of a galaxy with a stellar spectrum. We explicitly trace photon packages emerging from the nearby source and track the radiative and chemical effects of the multifrequency source (Ephoton = 0.76 eV → 7500 eV). We find that X-rays have a strongly negative feedback effect, compared to a stellar only source, when the radiative source is placed at a separation greater than ≳ 1 kpc. The X-rays heat the low and medium density gas in the envelope surrounding the collapsing halo suppressing the mass inflow. The result is a smaller enclosed mass compared to the stellar only case. However, for separations of ≲ 1 kpc, the feedback effects of the X-rays becomes somewhat neutral. The enhanced LW intensity at close separations dissociates more H2 and this gas is heated due to stellar photons alone, the addition of X-rays is then not significant. This distance dependence of X-ray feedback suggests that a Goldilocks zone exists close to a forming galaxy where X-ray photons have a much smaller negative feedback effect and ideal conditions exist for creating massive black hole seeds. [ABSTRACT FROM AUTHOR]

Background/aim: Fluid restriction has long been considered one of the cornerstones in self-care management of patients with heart failure. The aim of this discussion paper is to discuss fluid restriction in heart failure and propose advice about fluid intake in heart failure patients. Results: Although there have been seven randomised studies on fluid restriction in heart failure patients, the effect of fluid restriction on its own were only evaluated in two studies. In both studies, a stringent fluid restriction compared to a liberal fluid intake was not more beneficial with regard to clinical stability or body weight. In the other studies fluid restriction was part of a larger study intervention including, for example, individualised dietary recommendations and follow-up by telephone. Thus, the effect of fluid restriction on its own has been poorly evaluated. Conclusion: Fluid restriction should not be recommended to all heart failure patients. However, temporary fluid restriction can be considered in decompensated heart failure and/or patients with hyponatremia. Tailored fluid restriction based on body weight (30 ml/kg per day) seems to be most reasonable. To increase adherence to temporary fluid restriction, education, support and planned evaluations can be recommended. [ABSTRACT FROM AUTHOR]

The photodissociation of H2 by a nearby anisotropic source of radiation is seen as a critical component in creating an environment in which a direct collapse black hole may form. Employing radiative transfer we model the effect of multifrequency (0.76-60 eV) radiation on a collapsing halo at high redshift. We vary both the shape of the spectrum which emits the radiation and the distance to the emitting galaxy.We use blackbody spectra with temperatures of T = 104 K and 105 K and a realistic stellar spectrum. We find that an optimal zone exists between 1 and 4 kpc from the emitting galaxy. If the halo resides too close to the emitting galaxy the photoionizing radiation creates a large H II region which effectively disrupts the collapsing halo, too far from the source and the radiation flux drops below the level of the expected background and the H2 fraction remains too high. When the emitting galaxy is initially placed between 1 and 2 kpc from the collapsing halo, with a spectral shape consistent with a star-forming high-redshift galaxy, then a large central core forms. The mass of the central core is between 5000 and 10 000 M☉ at a temperature of approximately 1000 K. This core is however surrounded by a reservoir of hotter gas at approximately 8000 K, which leads to mass inflow rates of the order of ~0.1 M☉ yr-1. [ABSTRACT FROM AUTHOR]

Background Vitamin D (Vit D) is suggested to play a role in the regulation of physical function as well as in depression. Since, Vit D deficiency is common in patients with heart failure (HF), this study aims to explore if Vit D levels are associated with depressive symptoms and if this association is mediated by the patients' physical function. Method 506 HF patients (mean age 71, 38% women) were investigated. Depressive symptoms and physical function were measured with the Centre for Epidemiological Studies Depression Scale and the physical function scale from the RAND-36. Vit D was measured in blood samples Results At baseline there was no relationship between depressive symptoms and Vit D levels. However, at 18 months follow-up 29% of patients with Vit D < 50 nmol/l at baseline had depressive symptoms compared 19% of those with Vit D levels > 50 nmol/l (p < 0.05). Only in patients with Vit D < 50 nmol/l, Vit D correlated significantly to physical function and depressive symptoms (r = .29, p < 0.001 and r = .20, p < 0.01). In structural equation modelling an indirect association between Vit D and depressive symptoms was found, mediated by physical function (B = 0.20). This association was only found in patients with Vit D levels < 50 nmol/l. Conclusion In HF patients with Vit D < 50 nmol/l, Vit D is associated to depressive symptoms during follow-up and this association is mediated by physical function. This relationship is not found in patients with Vitamin D level > 50 nmol/l. [ABSTRACT FROM AUTHOR]

Background: A pre-specified meta-analysis of cardiovascular (CV) events from 21 phase 2b/3 dapagliflozin clinical trials was undertaken to characterise the CV profile of dapagliflozin. This showed no increase in CV risk with dapagliflozin compared with control (placebo or comparator treatment) with or without background glucose-lowering therapies. The analysis reported here aimed to characterise the CV profile of dapagliflozin in subgroups of patients in these 21 studies grouped by degree of CV risk, based on both baseline and in-study risk factors (including hypoglycaemic events), with a focus on major adverse CV events (MACE). Methods: Patients with type 2 diabetes, both overall and with different levels of CV risk, including CV disease (CVD) history, age and other CV risk factors, were analysed. A further analysis compared CV risk in patients who experienced a hypoglycaemic event prior to MACE and those who did not. Analyses were based on time to first event using a Cox proportional hazards model stratified by study comparing dapagliflozin versus control. Results: In total, 9339 patients were included in this meta-analysis; 5936 patients received dapagliflozin 2.5-10 mg (6668 patient-years) and 3403 received control (3882 patient-years). Dapagliflozin is not associated with increased CV risk and results further suggest the potential for a beneficial effect both in the overall population [Hazard Ratio (HR) 0.77; 95 % CI (0.54, 1.10) for MACE] and in those with a history of CVD [HR 0.80 (0.53, 1.22)]. These findings were consistent in patients with varying degrees of CV risk, including age, number and type of CVD events in medical history and number of CV risk factors present. Furthermore, there was no increased risk of MACE in patients who experienced a hypoglycaemic event compared with those who did not. Conclusions: There was no suggestion of increased risk for MACE with dapagliflozin compared with control in any of the populations investigated. In addition, the results suggest the potential for a beneficial CV effect which is consistent with the multifactorial benefits on CV risk factors associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. [ABSTRACT FROM AUTHOR]

A measurement setup for in situ sampling of internal relative humidity and temperature in concrete structures was developed. The setup was used to evaluate the moisture conditions and to determine whether drying of the concrete components within a nuclear reactor containment contributes to the moisture conditions. The measurement setup was tested for accuracy and thereafter installed in Swedish nuclear reactor containments for in situ monitoring. Results from the measurements confirmed that the setup is suitable, especially for long-term measurements at depths of 50 mm or more. Complementary moisture transport calculations showed that the moisture flux from the concrete to the interior of the reactor containment have a noticeable effect on the environmental conditions in the containments. The calculations of the moisture condition in the concrete show that 15–30% of the evaporable water in the concrete has been dried out during the 30 years of operation. [ABSTRACT FROM AUTHOR]

The relationship between the relative humidity and the moisture content of a material (for relative humidity levels close to 100%) can be studied using the pressure plate technique. However, this method is designed for desorption experiments and modifications are necessary in order to perform absorption experiments. This article presents a method to condition samples to a uniform moisture content by absorption with the pressure plate technique. The specimens were suspended in magnetic clamps until the ceramic plate had equilibrated with the applied pressure and modifications were made so that water could circulate through the pressure plate cell. [ABSTRACT FROM PUBLISHER]

Sovereignty and self-determination are central features of international relations and international law. The concepts are often depicted as conflicting and incompatible. In addition, the meaning, application and relevance of both concepts continue to form the subject of debate. In practice, they remain important, fiercely protected and centrally placed in conflicts concerning territorial integrity or political status. In this paper, we argue that our understanding of the concepts and their interrelationships can be enriched by looking past conventional and often rigid conceptualisations, instead placing more emphasis on the ways in which they are used in particular cases. The aim of this paper is to analyse how state sovereignty and peoples' right to self-determination are given meaning in state practice. The paper focuses on the case of Kosovo, and in particular statements submitted by 36 United Nations member states to the International Court of Justice. Analysing the ways in which states use the concepts to rationalize and justify their position on the Kosovo case reveals several diverging and sometimes conflicting understandings that indicate a need to go beyond and problematize the clear-cut and inflexible conceptualizations that often shape the academic debate on the concepts of state sovereignty and peoples' right of self-determination. [ABSTRACT FROM PUBLISHER]

The total mass of the Local Group and the masses of its primary constituents, the Milky Way (MW) and M31, are important anchors for several cosmological questions. Recent independent measurements have consistently yielded halo masses close to 1012M⊙ for the MW, and 1–2 × 1012M⊙ for M31, while estimates derived from the pair's kinematics via the 'timing argument' have yielded a combined mass of around 5 × 1012M⊙. We analyse the extremely large Uchuu simulation to constrain the mass of the Local Group and its two most massive members. First, we demonstrate the importance of selecting pairs whose kinematics reflect their mutual interactions. Adopting the observed separation and radial velocity, we obtain a weighted posterior of |$75_{-40}^{+65}$| km s−1 for the uncertain transverse velocity. Via Gaussian process regression, we infer a total mass of |$3.2^{+1.2}_{-0.9} \times 10^{12} \mathrm{M}_\odot$|⁠ , significantly below the timing argument value. Importantly, the remaining uncertainty is not rooted in the analysis or observational errors, but in the irreducible scatter in the kinematics–mass relation. We further find a mass for the less massive halo of |$0.9_{-0.3}^{+0.6} \times 10^{12} \mathrm{M}_\odot$| and for the more massive halo of |$2.3_{-0.9}^{+1.0} \times 10^{12} \mathrm{M}_\odot$|⁠ , consistent with independent measurements of the masses of MW and M31, respectively. Incorporating the MW mass as an additional prior let us constrain all measurements further and determine that the MW is very likely less massive than M31. [ABSTRACT FROM AUTHOR]

The article discusses how untreated patients with obstructive sleep apnea syndrome perceive their sleep situation and how it affects their life situation.

The article presents a study that explores whether nightly hypoxia contributed to the association between sleep-disordered breathing (SDB) and insomnia in community dwelling elderly with and without cardiovascular disease (CVD). The study included a total of 331 community-dwelling elderly aged 71-87 years underwent one-night polygraphic recordings. It suggests that SDB mediated by hypoxia in elderly with CVD can be associated with more insomnia and a worse prognosis.

We examine the impact of dark matter particle resolution on the formation of a baryonic core in high-resolution adaptive mesh refinement simulations. We test the effect that both particle smoothing and particle splitting have on the hydrodynamic properties of a collapsing halo at high redshift (z >20). Furthermore, we vary the background field intensity, with energy below the Lyman limit (<13.6 eV), as may be relevant for the case of metal-free star formation and supermassive black hole seed formation. We find that using particle splitting methods greatly increases our particle resolution without introducing any numerical noise and allows us to achieve converged results over a wide range of external background fields. Additionally, we find that for lower values of the background field a lower dark matter particle mass is required. We define the radius of the core as the point at which the enclosed baryonic mass dominates over the enclosed dark matter mass. For our simulations this results in Rcore ~5 pc. We find that in order to produce converged results which are not affected by dark matter particles requires that the relationship Mcore/MDM > 100.0 be satisfied, where Mcore is the enclosed baryon mass within the core and MDM is the minimum dark matter particle mass. This ratio should provide a very useful starting point for conducting convergence tests before any production run simulations. We find that dark matter particle smoothing is a useful adjunct to already highly resolved simulations. [ABSTRACT FROM AUTHOR]

An editorial is presented on the psychological distress such as depression and anxiety have been recognized as risk factors for poorer quality of life and a worse prognosis in patients with cardiovascular disease (CVD) and European Society of Cardiology guidelines on CVD prevention state.

To determine the durability of a lime–hemp concrete (LHC) wall and its resistance to driving rain, moisture conditions inside the wall have to be modelled. As model input, moisture transport properties were determined. Two LHC mixes were studied. Cup tests provided moisture diffusivity results at relative humidity (RH) values up to 95%. Capillary water uptake tests provided results for the interval 95–100% RH by means of curve fitting and the simulation tool JAM-KAP. A mix containing more lime showed higher moisture diffusivity at relative humidity >95%. [Copyright &y& Elsevier]

Objective. To investigate whether the effect of 48-month usage of coenzyme Q10 and selenium on cardiac function was different for participants with different levels of cardiac wall tension as measured by plasma levels of N-terminal natriuretic peptide (NT-proBNP) at baseline. Methods. A 48-month randomized double-blind controlled trial in a cohort of community-dwelling elderly (mean age 78 years) was carried out. A total of 443 participants were given coenzyme Q10 combined with selenium, or a placebo. NT-proBNP measured at baseline and 48 months was used to evaluate the cardiac wall tension. Results. After 48 months, supplementation of coenzyme Q10 and selenium had varying impacts depending on the severity of impairment of cardiac function. Analyses of the responses in the different quintiles of baseline NT-proBNP showed that those with active supplementation, and a plasma level of NT-proBNP in the second to fourth quintiles demonstrated significantly reduced NT-proBNP levels ( p = 0.022) as well as cardiovascular mortality after 48 months ( p = 0.006). Conclusion. Long-term supplementation of coenzyme Q10/selenium reduces NT-proBNP levels and cardiovascular mortality in those with baseline NT-proBNP in the second to fourth quintiles indicating those who gain from supplementation are patients with mild to moderate impaired cardiac function. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two lime–hemp mixes that can easily be reproduced were studied. [•] Sorption isotherms over the whole moisture range were determined for lime–hemp concrete. [•] Sorption isotherms included hysteresis. [•] Thermal properties were determined with a transient plane source method. [Copyright &y& Elsevier]

Abstract: Background: Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking. Methods: A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention. The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied. Results: During a follow up time of 5.2years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P =0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214ng/L vs. 302ng/L at 48months; P =0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P =0.03). Conclusion: Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography. [Copyright &y& Elsevier]

We experimentally demonstrate thatan incident light beam can becompletely annihilated in a single layer of randomly distributed,widely spaced gold nanoparticle antennas. Under certain conditions,each antenna dissipates more than 10 times the number of photons thatenter its geometric cross-sectional area. The underlying physics canbe understood in terms of a critical coupling to localized plasmonsin the nanoparticles or, equivalently, in terms of destructive opticalFano interference and so-called coherent absorption. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is unclear how depressive symptoms in patients with heart failure develop over time and whether this trajectory of depressive symptoms is associated with hospital admission and prognosis. Aim: To describe the time-course of depressive symptoms and determine the relationship with hospitalisation and mortality. Method: Data was analysed using 611 patients with completed CES-D questionnaires at baseline and at 18months. Data on hospitalisation was collected 18months after discharge and data on mortality was collected 18 and 36months post-discharge. Results: A total of 140 (61%) of the 229 patients with depressive symptoms at discharge had recovered from depressive symptoms after 18months whereas 71 (18%) of the 382 non-depressed developed depressive symptoms and 89 (39%) of the 229 depressed remained depressed. Patients with recently (i.e. during the last 18months) developed depressive symptoms showed a significantly higher risk for cardiovascular hospitalisation (HR 1.7, 95% CI 1.1–2.6, P =.016). After 36months, patients with developed depressive symptoms after discharge were at a higher risk of all-cause mortality (HR 2.0, 95% CI 1.2–3.5, P =.012) and there was a trend towards a higher risk of all-cause mortality in patients with ongoing depressive symptoms (HR 1.7, 95% CI 0.98–3.1, P =.056). Conclusion: A significant proportion of patients with HF, who were reported depressive symptoms at discharge recovered from depressive symptoms during the following 18months. However, patients who remained having depressive symptoms or patients who developed depressive symptoms had a worse prognosis. [Copyright &y& Elsevier]

The nonequilibrium distribution of electrons at thejunction of a scanning tunneling microscope is investigated by detecting photons with energies hv > eV, where V is the bias voltage. Electrons are found at energies exceeding the Fermi level by almost eV. While their distribution deviates from a Fermi-Dirac function it is consistent with a model of hot electrons and holes that diffuse in energy and real space. [ABSTRACT FROM AUTHOR]