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In a high-energy fragmentation experiment at GSI an I=π(6+) isomer and its γ-decay are identified in 102Sn, the two-neutron neighbour of the doubly-magic 100Sn. Its half-life is measured to be T=1/2367(11) ns. The possible existence of further isomers is discussed in the framework of large-scale shell model (LSSM) calculations including up to five particle-hole excitations of the 100Sn core. From the precise B(E2; 6+→4+) strength and the recently remeasured value for B(E2; 8+→6+) in the two-proton hole neighbour 98Cd effective E2 polarization charges for protons and neutrons were inferred including LSSM corrections within the full N=4 0ħω space. The results are discussed in comparison to predicted and empirically determined effective operators.

The γ-ray emission from the nuclei 62,64Fe following Coulomb excitation at bombarding energy of 400-440 AMeV was measured with special focus on E1 transitions in the energy region 4-8 MeV. The unstable neutron-rich nuclei 62,64Fe were produced at the FAIR-GSI laboratories and selected with the FRS spectrometer. The γ decay was detected with AGATA. From the measured γ-ray spectra the summed E1 strength is extracted and compared to microscopic quasi-particle phonon model calculations. The trend of the E1 strength with increasing neutron number is found to be fairly well reproduced with calculations that assume a rather complex structure of the 1− states (three-phonon states) inducing a strong fragmentation of the E1 nuclear response below the neutron binding energy.

The lifetimes of the low-lying excited states 2+ and 4+ have been directly measured in the neutron-deficient 106,108Sn isotopes. The nuclei were populated via a deep-inelastic reaction and the lifetime measurement was performed employing a differential plunger device. The emitted γ rays were detected by the AGATA array, while the reaction products were uniquely identified by the VAMOS++ magnetic spectrometer. Large-Scale Shell-Model calculations with realistic forces indicate that, independently of the pairing content of the interaction, the quadrupole force is dominant in the B(E2;21+→0g.s.+) values and it describes well the experimental pattern for 104−114Sn; the B(E2;41+→21+) values, measured here for the first time, depend critically on a delicate pairing-quadrupole balance, disclosed by the very precise results in 108Sn.

A lifetime measurement of the 19/2− state in 207Pb has been performed using the Recoil Distance Doppler-Shift (RDDS) method. The nuclei of interest were produced in multi-nucleon transfer reactions induced by a 208Pb beam impinging on a 100Mo enriched target. The beam-like nuclei were detected and identified in terms of their atomic mass number in the VAMOS++ spectrometer while the prompt γ rays were detected by the AGATA tracking array. The measured large reduced transition probability B(E3,19/2−→13/2+)=40(8) W.u. is the first indication of the octupole phonon at high spin in 207Pb. An analysis in terms of a particle-octupole-vibration coupling model indicates that the measured B(E3) value in 207Pb is compatible with the contributions from single-phonon and single particle E3 as well as E3 strength arising from the double-octupole-phonon 6+ state, all adding coherently. A crucial aspect of the coupling model, namely the strong mixing between single-hole and the phonon-hole states, is confirmed in a realistic shell-model calculation. Keywords: AGATA spectrometer, γ-Ray tracking, VAMOS++ spectrometer, Plunger device, Nuclear deformation, Octupole phonon

Electric quadrupole matrix elements, Mp, for the Jπ=2+→0+, ΔT=0, T=1 transitions across the A=46 isobaric multiplet 46Cr-46V-46Ti have been measured at GSI with the FRS-LYCCA-AGATA setup. This allows direct insight into the isospin purity of the states of interest by testing the linearity of Mp with respect to Tz. Pairs of nuclei in the T=1 triplet were studied using identical reaction mechanisms in order to control systematic errors. The Mp values were obtained with two different methodologies: (i) a relativistic Coulomb excitation experiment was performed for 46Cr and 46Ti; (ii) a “stretched target” technique was adopted here, for the first time, for lifetime measurements in 46V and 46Ti. A constant value of Mp across the triplet has been observed. Shell-model calculations performed within the fp shell fail to reproduce this unexpected trend, pointing towards the need of a wider valence space. This result is confirmed by the good agreement with experimental data achieved with an interaction which allows excitations from the underlying sd shell. A test of the linearity rule for all published data on complete T=1 isospin triplets is presented.

Introduction: The risk of suicide has been shown to vary by occupation. We aim to identify contemporary occupational groups at greatest risk for suicidal behaviour (fatal and non-fatal), in Swedish men of working-age., Methods: A population-based cohort study of male conscripts without history of self-harm who enlisted during 1968-2001 and were followed-up during 2002-2019 (n = 1 542 665). Occupational groups and suicidal behaviours were identified using national registers. Incidence rate ratios (IRR) for suicidal behaviour at ages 25-65 were calculated among occupational groups, and compared to the incidence rate of the whole cohort., Results: Major occupational groups with increased risk for suicidal behavior included elementary occupations, building and manufacturing, service, care and shop sale and mechanical manufacturing and transport. Subgroup analyses revealed particularly high risks for assistant nurses, other service workers not elsewhere classified, building frame and related trades workers and cleaners and helpers., Conclusions: Men with elementary occupations as well as personal care and building and manufacturing workers were at greatest risk. This study provides a comprehensive description of risks for suicidal behaviour among occupational groups in men of working-age. These results suggest occupational groups that should be targeted for general suicide prevention intervention., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures involving human subjects were approved by the Ethics Committee of the University of Gothenburg (462–14) and Confidentiality Clearance at Statistics Sweden. Given that all data used was psuedonymized and coded by Statistics Sweden, informed consent to participate was not obtained from the participants. Consent for publication: Not applicable for Swedish register-based studies, as the contribution of personal data to research is included in the contract between Swedish residents and the Swedish state provided that the research is ethically conducted [36]. The Ethical committees in Sweden are generally acknowledged to represent the public, and approval from an Ethical committee can largely replace individual approvals from study participants in registry-based research. As stated by Ludvigsson et al. [36], the arguments that informed consent is not needed for registry-based studies in Sweden include: 1) Many research proposals would be impossible due to the sheer number of study participants (over 1 million participants); 2) It would dramatically reduce rate of participation and statistical power of most nationwide population-based studies, and lessen the scientific validity; 3) Risk for selection bias, since consent would be notably harder to obtain in high-risk groups, where positive outcomes are most frequent; 4) Individuals with registry-based information will be dead when the study is performed, and thus, consent is impossible; 5) Most large-scale research would be prohibited due to the extreme costs of obtaining the consent of millions of individuals with health data. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: The aim of this prospective cohort study was to investigate the associations between changes in cardiorespiratory fitness (CRF) and the risk of colorectal and prostate cancer in men., Methods: Data from men who completed a health assessment both in military conscription in youth and an occupational health profile assessment (HPA) later in life were used. CRF was assessed as estimated V̇O 2max , using a cycle ergometer fitness test at both time points. We linked the assessment data to national register data on colorectal and prostate cancer incidence, and hazard ratios and confidence intervals were estimated using Cox proportional hazard regression., Results: 139,764 men with a mean age of 18 (SD 0.6) at conscription and 43 (SD 8.9) at HPA were included. The average time between the two assessments was 25.9 (SD 9.0) years and mean follow-up time following HPA test was 10.0 (SD 5.6) years for prostate and colorectal cancer. Annual percentage change in relative and absolute V̇O 2max from conscription to HPA was inversely associated with the risk of colorectal cancer incidence, hazard ratio of 0.83 (95% CI [0.72-0.94]) and 0.88 (95% CI [0.79-0.99]), respectively. These associations were driven by data from individuals in the lowest and moderate level fitness tertials at conscription. Change in CRF was not associated with prostate cancer incidence risk., Conclusions: Changes in, not only level of, CRF from youth to adulthood are related to colorectal cancer incidence risk and therefore, improving CRF should be considered as an important colorectal cancer risk reduction strategy., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: High cardiorespiratory fitness (CRF) has been associated with a lower risk of depression, anxiety, and cerebrovascular disease. The aim was to explore CRF changes over-time associated with these outcomes., Methods: This large-scale prospective cohort study, using data from Swedish population-wide registries and databases (during 1972-2020), included men (n=131,431), with measures of estimated CRF (estCRF) in late adolescence (maximal cycle test) and adulthood (submaximal cycle test) (mean years between 24.6, SD 8.8). The study explored how change in estCRF was associated with incident depression, anxiety, and cerebrovascular disease using Cox proportional hazards models. Analyses were performed in 2023., Results: Higher estCRF in late adolescence and adulthood were associated with a lower risk of incident depression, anxiety, and cerebrovascular disease later in life. For all three outcomes, an increase in estCRF (mL/min/kg and z-score) between the two-time points was associated with a lower risk. Further, decreasing from moderate or high estCRF in adolescence to low estCRF in adulthood, compared to staying at a moderate or high level, was associated with a higher risk of depression and anxiety (HR: 1.24 95% CI 1.07-1.45 and 1.25 95% CI 1.06-1.49, respectively). Conversely, increasing from moderate to high estCRF was associated with a lower risk of incident anxiety (HR: 0.84 95% CI 0.71-0.99)., Conclusions: The findings indicate that there is a longitudinal association between negative change in estCRF and increased risk of depression, anxiety, and cerebrovascular disease later in life. Decreasing levels of estCRF could be a helpful indicator when identifying these disorders at a population level., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the associations between stress resilience in late adolescence and later risk of severe COVID-19 and other lower respiratory infections. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection., Methods: We conducted a registry-based cohort study of 1.4 million Swedish men, undergoing military conscription between 1968 and 2005. All were assessed by a psychologist for stress resilience, receiving a score between 1 and 9. The outcomes were hospitalization or death due to COVID-19 from March 2020 to September 2021 and hospitalization due to bacterial or viral pneumonia from conscription until January 2020. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection., Results: Poor stress resilience in late adolescence is associated with later risk of severe lower respiratory infections. Using a high resilience score as the reference, the hazard ratio (95 % CI) for death due to COVID-19 for the lowest scores was 1.49 (1.01-2.18) adjusted for CRF and other confounders. The corresponding adjusted hazard ratios for hospitalization due to bacterial pneumonia were 2.28 (2.03-2.57) and for viral pneumonia 1.92 (1.33-2.79). No significant interaction was seen between stress resilience and CRF in the analysis., Conclusions: Poor stress resilience is a prospective factor for severe COVID-19 as well as for bacterial and viral respiratory pneumonia endpoints, independent of CRF. These findings imply an effect of late adolescent stress resilience on the immune system later in life., Competing Interests: Declaration of competing interest All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The clinical utility of regional strain measurements in echocardiography is challenged by suboptimal reproducibility. In this study, we aimed to evaluate the test-retest reproducibility of regional longitudinal strain (RLS) per coronary artery perfusion territory (RLS Territory ) and basal-to-apical level of the left ventricle (RLS Level ), measured by a novel fully automated deep learning (DL) method based on point tracking., Methods and Results: We measured strain in a dual-centre test-retest data set that included 40 controls and 40 patients with suspected non-ST elevation acute coronary syndrome. Two consecutive echocardiograms per subject were recorded by different operators. The reproducibility of RLS Territory and RLS Level measured by the DL method and by three experienced observers using semi-automatic software (2D Strain, EchoPAC, GE HealthCare) was evaluated as minimal detectable change (MDC). The DL method had MDC for RLS Territory and RLS Level ranging from 3.6 to 4.3%, corresponding to a 33-35% improved reproducibility compared with the inter- and intraobserver scenarios (MDC 5.5-6.4% and 4.9-5.4%). Furthermore, the DL method had a lower variance of test-retest differences for both RLS Territory and RLS Level compared with inter- and intraobserver scenarios (all P < 0.001). Bland-Altman analyses demonstrated superior reproducibility by the DL method for the whole range of strain values compared with the best observer scenarios. The feasibility of the DL method was 93% and measurement time was only 1 s per echocardiogram., Conclusion: The novel DL method provided fully automated measurements of RLS, with improved test-retest reproducibility compared with semi-automatic measurements by experienced observers. RLS measured by the DL method has the potential to advance patient care through a more detailed, more efficient, and less user-dependent clinical assessment of myocardial function., Competing Interests: Conflict of interest: A.Ø., S.O., E.S., L.L., H.D., and B.G. hold positions at the Centre for Innovative Ultrasound Solutions (CIUS)—a Norwegian Research Council (NRC) centre for research-based innovation, where GE HealthCare, Horten, Norway, is one of the institutional partners. J.N., A.Ø., T.E., K.H.H., L.L., H.D., and B.G. hold positions at the PrecisionHealth Center for optimized cardiac care (ProCardio)—another NRCcentre for research-based innovation, where GE HealthCare is a partner. L.L. acts as a part-time consultant for GE HealthCare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

School psychology graduate students experience many risk factors for problems with mental health, including high workloads, financial distress, and challenging relationships with faculty that can exacerbate feelings of anxiety and depression. Although there have been studies that have investigated depression and anxiety amongst graduate students in general (Eisenberg et al., 2007) and health service psychology students in particular (Hobaica et al., 2021), there are reasons to believe that school psychology graduate students may have different experiences. To date, no research has been found investigating the depression and anxiety symptoms of graduate students in school psychology programs. A survey was sent to 194 school psychology training programs, and 291 graduate students completed it. Approximately one in four graduate students reported moderate to severe levels of depressive symptoms, while one in three reported moderate to severe levels of anxiety symptoms. These symptoms were significantly higher in graduate students identifying as lesbian, gay, bisexual, transgender, queer/questioning, and more identities, women, or reported being from a lower socioeconomic background. There were no differences in depression or anxiety symptoms between the type of program (i.e., doctoral or specialist) or years in program. Implications for trainers of school psychology are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose of Review: Several innovative digital technologies have begun to be applied to diagnosing and treating migraine. We reviewed the potential benefits and opportunities from delivering migraine care through comprehensive digital clinics., Recent Findings: There are increasing applications of digitization to migraine diagnosis and management, including e-diaries, and patient self-management, especially after the COVID-19 pandemic. Digital care delivery appears to better engage chronic migraine sufferers who may struggle to present to physical clinics., Summary: Digital clinics appear to be a promising treatment modality for patients with chronic migraine. They potentially minimize travel time, shorten waiting periods, improve usability, and increase access to neurologists. Additionally, they have the potential to provide care at a much lower cost than traditional physical clinics. However, the current state of evidence mostly draws on case-reports, suggesting a need for future randomized trials comparing digital interventions with standard care pathways., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Exercise interventions show promise in the treatment of anxiety disorders, but effects on health-related quality of life (HR-QoL), work ability, and sick leave are little studied. We investigated these outcomes in a 12-week randomized controlled trial with a 1-year follow-up., Methods: Patients aged 18-65 (n = 222) with anxiety disorders from primary care centers in Gothenburg were randomized to a control group or one of two 12-week exercise intervention groups (low-intensity, [LI] and moderate/high-intensity, [HI]); 148 were evaluated at 12-weeks and 113 completed the 1-year follow-up. The EuroQol 5D (EQ5D; index and the visual analogue scale [VAS]), work ability score (WAS), presenteeism, and self-reported sick leave were assessed at baseline, 12 weeks, and 1 year. Improvements were defined by binary cut-offs for each scale. Binary logistic regression with odds ratios (OR) and 95 % confidence intervals (CI) were reported., Results: There were improved scores for EQ5D and WAS in the HI group compared to controls after 12 weeks (EQ5D index: 4.74 [1.91-11.7], EQ5D-VAS 4.00, [1.65-9.72], WAS 3.41 [1.24-7.37]) and 1 year (EQ5D index: 3.05 [1.05-8.81], EQ5D-VAS 3.20 [1.16-8.84], WAS 5.50 [1.85-16.3]). Post-hoc analysis showed higher ORs in participants on antidepressants (n = 75) (12-week EQ5D index: OR 9.95 [2.85-34.8]) and significant improvements in EQ5D scores for both intervention groups after 1 year. There were no between-group differences for presenteeism or sick leave., Limitations: Discontinuation was high, mostly early after randomization (n = 74), as is common for anxiety interventions., Conclusions: HI Exercise improves HR-QoL and work ability in anxiety patients, especially when combined with antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The full random-effects model (FREM) is an innovative and relatively novel covariate modeling technique. It differs from other covariate modeling approaches in that it treats covariates as observations and captures their impact on model parameters using their covariances. These unique characteristics mean that FREM is insensitive to correlations between covariates and implicitly handles missing covariate data. In practice, this implies that covariates are less likely to be excluded from the modeling scope in light of the observed data. FREM has been shown to be a useful modeling method for small datasets, but its pre-specification properties make it a very compelling modeling choice for late-stage phases of drug development. The present tutorial aims to explain what FREM models are and how they can be used in practice., (© 2024 Pharmetheus AB. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Cardiac valve event timing plays a crucial role when conducting clinical measurements using echocardiography. However, established automated approaches are limited by the need of external electrocardiogram sensors, and manual measurements often rely on timing from different cardiac cycles. Recent methods have applied deep learning to cardiac timing, but they have mainly been restricted to only detecting two key time points, namely end-diastole (ED) and end-systole (ES). In this work, we propose a deep learning approach that leverages triplane recordings to enhance detection of valve events in echocardiography. Our method demonstrates improved performance detecting six different events, including valve events conventionally associated with ED and ES. Of all events, we achieve an average absolute frame difference (aFD) of maximum 1.4 frames (29 ms) for start of diastasis, down to 0.6 frames (12 ms) for mitral valve opening when performing a ten-fold cross-validation with test splits on triplane data from 240 patients. On an external independent test consisting of apical long-axis data from 180 other patients, the worst performing event detection had an aFD of 1.8 (30 ms). The proposed approach has the potential to significantly impact clinical practice by enabling more accurate, rapid and comprehensive event detection, leading to improved clinical measurements.

The inclusion of covariates in pharmacometric models is important due to their ability to explain variability in drug exposure and response. Clear communication of the impact of covariates is needed to support informed decision making in clinical practice and in drug development. However, effectively conveying these effects to key stakeholders and decision makers can be challenging. Forest plots have been proposed to meet these communication needs. However, forest plots for the illustration of covariate effects in pharmacometrics are complex combinations of model predictions, uncertainty estimates, tabulated results, and reference lines and intervals. The purpose of this tutorial is to outline the aspects that influence the interpretation of forest plots, recommend best practices, and offer specific guidance for a clear and transparent communication of covariate effects., (© 2024 Pharmetheus AB. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aims: Left atrial (LA) and ventricular (LV) remodelling is thought to be balanced in healthy individuals, and the LA end-systolic volume (LAV) to LV end-diastolic volume (LVEDV) ratio (LA:LV) could help discriminate between pathological and physiological LA enlargement. We aimed to assess LA:LV and its associations with age, sex, and cardiovascular risk factors HbA1C, body mass index (BMI), systolic blood pressure, and peak oxygen uptake (VO 2peak ). The association to measures of LV diastolic function and filling pressures were compared with LAV and LA reservoir strain., Methods and Results: Cardiopulmonary exercise testing and measurement of risk factors 10 years apart and echocardiography at follow-up was performed in 1348 healthy adults [52% women, mean (SD) age 59 (12) years] prospectively included in a large population study. All risk factors were significantly associated with LA:LV in univariate analyses, while BMI and VO 2peak were significantly associated with LA:LV in adjusted models. A higher LA:LV was associated with increased odds ratio (OR) of diastolic dysfunction [OR (95% CI) 2.6 (2.1, 3.3)]. Measures of LV filling pressures were more closely associated with LA:LV than LAV and LA reservoir strain, but LA reservoir strain was more closely related to some diastolic function measures. In individuals with LAV > 34 mL/m 2 , the LA:LV explained 29% of variance in VO 2peak ( P < 0.001)., Conclusion: A higher LA:LV was associated with, and may improve, assessment of diastolic dysfunction and filling pressures. The LA:LV differentiates VO 2peak in individuals with enlarged LAV and may have a role in evaluating whether LA enlargement reflects pathology., Competing Interests: Conflict of interest Institutional partnership with GE Ultrasound in the Centre for Innovative Ultrasound Solutions. H.D. has a research contract with GE Ultrasound and has received consulting fees and/or honoraria from Boehringer Ingelheim, Bristol Myers Squibb, Bayer, and Pfizer. None of the disclosures were related to this work. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: The right ventricle receives less attention than its left counterpart in echocardiography research, practice and development of automated solutions. In the work described here, we sought to determine that the deep learning methods for automated segmentation of the left ventricle in 2-D echocardiograms are also valid for the right ventricle. Additionally, here we describe and explore a keypoint detection approach to segmentation that guards against erratic behavior often displayed by segmentation models., Methods: We used a data set of echo images focused on the right ventricle from 250 participants to train and evaluate several deep learning models for segmentation and keypoint detection. We propose a compact architecture (U-Net KP) employing the latter approach. The architecture is designed to balance high speed with accuracy and robustness., Results: All featured models achieved segmentation accuracy close to the inter-observer variability. When computing the metrics of right ventricular systolic function from contour predictions of U-Net KP, we obtained the bias and 95% limits of agreement of 0.8 ± 10.8% for the right ventricular fractional area change measurements, -0.04 ± 0.54 cm for the tricuspid annular plane systolic excursion measurements and 0.2 ± 6.6% for the right ventricular free wall strain measurements. These results were also comparable to the semi-automatically derived inter-observer discrepancies of 0.4 ± 11.8%, -0.37 ± 0.58 cm and -1.0 ± 7.7% for the aforementioned metrics, respectively., Conclusion: Given the appropriate data, automated segmentation and quantification of the right ventricle in 2-D echocardiography are feasible with existing methods. However, keypoint detection architectures may offer higher robustness and information density for the same computational cost., Competing Interests: Conflict of interest S.A.A. holds a full-time position at GE Vingmed Ultrasound AS, Horten, Norway. L.L. is a part-time consultant at GE Vingmed Ultrasound AS, Horten, Norway., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: While suicidal behaviour has become less prevalent in non-manual workers in recent decades, rates have increased in manual workers. We aimed to identify occupations within the construction industry with excess risk of suicide and non-fatal self-harm., Methods: This cohort of Swedish construction workers comprises 389 132 individuals examined 1971-1993 and followed 1987-2018 using national hospital and cause of death registers. More than 200 job titles were merged into 22 occupational groups. For 296 891 men alive in 1987 and active in the construction sector, survival was calculated from baseline to first event of non-fatal self-harm or suicide and censored for emigration, long-term unemployment, disability pension, retirement, death from other causes or end of follow-up. HRs with 95% CIs were obtained from multiple Cox proportional hazard regression., Results: Overall, 1618 cases of suicide and 4774 events of non-fatal self-harm were registered. Self-harm before baseline was the single largest risk factor for suicide, HR 9.3 (95% CI 7.5 to 11.6). Compared with the overall mean, labourers and rock workers had excess risk for suicide, HR 1.4 (95% CI 1.1 to 1.7) and 1.5 (95% CI 1.0 to 2.3), respectively, while electricians, clerks and foremen had reduced risk. Labourers, concrete workers, sheet metal workers, painters, glaziers and the group 'other construction workers' were at increased risk for non-fatal self-harm. Almost all categories of manual workers were at increased risk for suicidal behaviour relative to clerks and foremen., Conclusions: Specific occupations within the construction sector were associated with excess risk for suicidal behaviour. Future studies should identify underlying risk factors to inform tailored interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Both Alzheimer's disease and vascular dementia are the result of disease processes that typically develop over several decades. Population studies have estimated that more than half of the risk for dementia is preventable or at least modifiable through behavioral adaptations. The association between these lifestyle factors and the risk of dementia is most evident for exposure in midlife. However, habits formed in middle age often reflect a lifetime of behavior patterns and living conditions. Therefore, individuals who, for example, are able to maintain healthy diets and regular exercise during their middle years are likely to benefit from these cognition-protective habits they have practiced throughout their lives. For numerous adult diseases, significant risks can often be traced back to early childhood. Suboptimal conditions during the perinatal period, childhood and adolescence can increase the risk of adult diseases, including stroke, heart disease, insulin resistance, hypertension and dementia. This review aims at summarizing some of the evidence for dementia risks from a life-time perspective with the goal of raising awareness for early dementia prevention and successful aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Marzeptacog alfa (MarzAA) is under development for subcutaneous treatment of episodic bleeds in patients with hemophilia A/B and was studied in a phase III trial evaluating MarzAA compared with standard-of-care (SoC) for on-demand use. The work presented here aimed to evaluate MarzAA and SoC treatment of bleeding events on a standardized four-point efficacy scale (poor, fair, good, and excellent). Two continuous-time Markov modeling approaches were explored; a four-state model analyzing all four categories of bleeding improvement and a two-state model analyzing a binarized outcome (treatment failure (poor/fair), and treatment success (good/excellent)). Different covariates impacting improvement of bleeding episodes as well as a putative relationship between MarzAA exposure and improvement of bleeding episodes were evaluated. In the final four-state model, higher baseline diastolic blood pressure and higher age (> 33 years of age) were found to negatively and positively impact improvement of bleeding condition, respectively. Bleeding events occurring in knees and ankles were found to improve faster than bleeding events at other locations. The covariate effects had most impact on early treatment success (≤ 3 hours) whereas at later timepoints (> 12 hours), treatment success was similar for all patients indicating that these covariates might be clinically relevant for early treatment response. A statistically significant relationship between MarzAA zero-order absorption and improvement of bleedings (P < 0.05) were identified albeit with low precision. No statistically significant difference in treatment response between MarzAA and intravenous SoC was identified, indicating the potential of MarzAA for treatment of episodic bleeding events with a favorable subcutaneous administration route., (© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

During drug development, a key step is the identification of relevant covariates predicting between-subject variations in drug response. The full random effects model (FREM) is one of the full-covariate approaches used to identify relevant covariates in nonlinear mixed effects models. Here we explore the ability of FREM to handle missing (both missing completely at random (MCAR) and missing at random (MAR)) covariate data and compare it to the full fixed-effects model (FFEM) approach, applied either with complete case analysis or mean imputation. A global health dataset (20 421 children) was used to develop a FREM describing the changes of height for age Z-score (HAZ) over time. Simulated datasets (n = 1000) were generated with variable rates of missing (MCAR) covariate data (0%-90%) and different proportions of missing (MAR) data condition on either observed covariates or predicted HAZ. The three methods were used to re-estimate model and compared in terms of bias and precision which showed that FREM had only minor increases in bias and minor loss of precision at increasing percentages of missing (MCAR) covariate data and performed similarly in the MAR scenarios. Conversely, the FFEM approaches either collapsed at ≥ $$ \ge $$ 70% of missing (MCAR) covariate data (FFEM complete case analysis) or had large bias increases and loss of precision (FFEM with mean imputation). Our results suggest that FREM is an appropriate approach to covariate modeling for datasets with missing (MCAR and MAR) covariate data, such as in global health studies., (© 2023 Pharmetheus AB and The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

The excited states of unstable ^{20}O were investigated via γ-ray spectroscopy following the ^{19}O(d,p)^{20}O reaction at 8  AMeV. By exploiting the Doppler shift attenuation method, the lifetimes of the 2&#95;{2}^{+} and 3&#95;{1}^{+} states were firmly established. From the γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2&#95;{2}^{+} and 3&#95;{1}^{+} states, the B(E2) and B(M1) were determined. Various chiral effective field theory Hamiltonians, describing the nuclear properties beyond ground states, along with a standard USDB interaction, were compared with the experimentally obtained data. Such a comparison for a large set of γ-ray transition probabilities with the valence space in medium similarity renormalization group ab initio calculations was performed for the first time in a nucleus far from stability. It was shown that the ab initio approaches using chiral effective field theory forces are challenged by detailed high-precision spectroscopic properties of nuclei. The reduced transition probabilities were found to be a very constraining test of the performance of the ab initio models.

Background: Recommendations for statistical methods in rare disease trials are scarce, especially for cross-over designs. As a result various state-of-the-art methodologies were compared as neutrally as possible using an illustrative data set from epidermolysis bullosa research to build recommendations for count, binary, and ordinal outcome variables. For this purpose, parametric (model averaging), semiparametric (generalized estimating equations type [GEE-like]) and nonparametric (generalized pairwise comparisons [GPC] and a marginal model implemented in the R package nparLD) methods were chosen by an international consortium of statisticians., Results: It was found that there is no uniformly best method for the aforementioned types of outcome variables, but in particular situations, there are methods that perform better than others. Especially if maximizing power is the primary goal, the prioritized unmatched GPC method was able to achieve particularly good results, besides being appropriate for prioritizing clinically relevant time points. Model averaging led to favorable results in some scenarios especially within the binary outcome setting and, like the GEE-like semiparametric method, also allows for considering period and carry-over effects properly. Inference based on the nonparametric marginal model was able to achieve high power, especially in the ordinal outcome scenario, despite small sample sizes due to separate testing of treatment periods, and is suitable when longitudinal and interaction effects have to be considered., Conclusion: Overall, a balance has to be found between achieving high power, accounting for cross-over, period, or carry-over effects, and prioritizing clinically relevant time points., (© 2023. The Author(s).)

Background: Myocardial deformation by echocardiographic strain imaging is a key measurement in cardiology, providing valuable diagnostic and prognostic information. Reference ranges for strain should be established from large healthy populations with minimal methodologic biases and variability., Objectives: The aim of this study was to establish echocardiographic reference ranges, including lower normal limits of global strains for all 4 cardiac chambers, by guideline-directed dedicated views from a large healthy population and to evaluate the influence of subject-specific characteristics on strain., Methods: In total, 1,329 healthy participants from HUNT4Echo, the echocardiographic substudy of the 4th wave of the Trøndelag Health Study, were included. Echocardiographic recordings specific for each chamber were optimized according to current recommendations. Two experienced sonographers recorded all echocardiograms using GE HealthCare Vivid E95 scanners. Analyses were performed by experts using GE HealthCare EchoPAC., Results: The reference ranges for left ventricular (LV) global longitudinal strain and right ventricular free-wall strain were -24% to -16% and -35% to -17%, respectively. Correspondingly, left atrial (LA) and right atrial (RA) reservoir strains were 17% to 49% and 17% to 59%. All strains showed lower absolute values with higher age, except for LA and RA contractile strains, which were higher. The feasibility for strain was overall good (LV 96%, right ventricular 83%, LA 94%, and RA 87%). All chamber-specific strains were associated with age, and LV strain was associated with sex., Conclusions: Reference ranges of strain for all cardiac chambers were established based on guideline-directed chamber-specific recordings. Age and sex were the most important factors influencing reference ranges and should be considered when using strain echocardiography., Competing Interests: Funding Support and Author Disclosures This work was supported by the Centre for Innovative Ultrasound Solutions, The Central Norway regional health authority, the ProCardio Center for Innovation, St. Olavs University Hospital, Nord-Trøndelag Hospital Trust, grants from the Simon Fougner Hartmann Family Fund, Denmark, and the Norwegian University of Science and Technology. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The communication skills of healthcare professionals play a crucial role in successful shared decision-making with parents in neonatal intensive care. Improving communication skills can be achieved through practice and reflection on personal experiences after authentic interaction events with parents. The process of reflection typically involves three phases: description, reflection, and critical reflection. In this study, our aim was to explore the acceptability of the Reflective Group Dialogue intervention and its effectiveness in supporting the reflective process., Methods: This qualitative pilot study was conducted in the neonatal intensive care unit at Uppsala University Children's Hospital, Sweden. The sample consisted of nine medical rounds with seven families, five neonatologists, seven registered nurses, and five assistant nurses. Purposive sampling was used to collect the data. The intervention comprised four elements: (1) before the intervention, a recorded presentation on shared decision-making was given to the entire unit staff, (2) an observation of a normal medical round discussion with parents, (3) an interview with parents about their experience after the same round, and (4) a reflective discussion with the participating health care professionals after the round. The parent interviews and reflective discussions were audio-recorded and transcribed verbatim. They were analyzed using thematic analysis as a theoretical strategy., Results: Both parents and staff widely accepted the intervention and found it beneficial. We identified four discussions that remained in the descriptive phase of the reflection process, four that reached the reflective phase, and one that reached the critical reflection phase. The descriptive discussions were characterized by using a single perspective to reflect, often based on personal opinions. The reflective discussions included analyzing interaction sequences from both staff and parent perspectives and were primarily based on actual observations of communication during medical rounds. The critical discussion led to a new awareness of current practices concerning parental involvement in decision-making. These discussions also utilized "what-if" thinking to evaluate potential new practices and their pros and cons., Conclusions: The intervention seems promising as it was perceived as beneficial by the recipients and facilitated reflection in most cases. However, to enhance the feasibility of the intervention, some improvements are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ahlqvist-Björkroth, Thernström Blomqvist, Nyberg, Normann and Axelin.)