Role of disorder in the size-scaling of material strength

We study the sample size dependence of the strength of disordered materials with a flaw, by numerical simulations of lattice models for fracture. We find a crossover between a regime controlled by the fluctuations due to disorder and another controlled by stress-concentrations, ruled by continuum fracture mechanics. The results are formulated in terms of a scaling law involving a statistical fracture process zone. Its existence and scaling properties are only revealed by sampling over many configurations of the disorder. The scaling law is in good agreement with experimental results obtained from notched paper samples.Comment: 4 pages 5 figure

Intraoperative Complications and Mid-Term Follow-Up of Large-Diameter Head Metal-on-Metal Total Hip Arthroplasty and Hip Resurfacing Arthroplasty

Background and Aims: Large-diameter head total hip arthroplasty and hip resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the treatment of hip osteoarthritis. The aim of this retrospective study was to investigate the mid-term survival of large-diameter head total hip arthroplasty patients operated on in three university hospitals and to compare these results to the survival of hip resurfacing arthroplasty patients. Material and Methods: A total of 3860 hip arthroplasties (3029 large-diameter head total hip arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757 patients) were operated on between January 2004 and December 2009. The mean follow-up was 4.3years (range: 0.3-8.0years) in the total hip arthroplasty group and 5.1years (range: 1.7-7.9years) in the hip resurfacing arthroplasty group. Cox multiple regression model and Kaplan-Meier survival analysis were used to study the survival of the total hip arthroplasties and the hip resurfacing arthroplasties. Intraoperative complications and reasons for revisions were also evaluated. Results: In Cox regression analysis, the hazard ratio for revision of hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip arthroplasty (95% confidence interval: 1.0-2.2) (p=0.029). The cumulative Kaplan-Meier survival rate was 90.7% at 7.7years for the large-diameter head total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6). There were a total of 166/3029 (5.5%) intraoperative complications in the large-diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip resurfacing arthroplasty group (p=0.001). Revision for any reason was performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing arthroplasty group (p=0.04). Conclusion: The mid-term survival of both of these devices was poor, and revisions due to adverse reactions to metal debris will most likely rise at longer follow-up. There were more intraoperative complications in the large-diameter head total hip arthroplasty group than in the hip resurfacing arthroplasty group.Peer reviewe

Longitudinal Associations of High-Volume and Vigorous-Intensity Exercise With Hip Fracture Risk in Men

Maintenance of vigorous exercise habits from young to old age is considered protective against hip fractures, but data on fracture risk in lifelong vigorous exercisers are lacking. This longitudinal cohort study examined the hazard of hip fractures in 1844 male former athletes and 1216 population controls and in relation to exercise volume and intensity in later years. Incident hip fractures after age 50 years were identified from hospital discharge register from 1972 to 2015. Exercise and covariate information was obtained from questionnaires administered in 1985, 1995, 2001, and 2008. Analyses were conducted using extended proportional hazards regression model for time-dependent exposures and effects. During the mean +/- SD follow-up of 21.6 +/- 10.3 years, 62 (3.4%) athletes and 38 (3.1%) controls sustained a hip fracture. Adjusted hazard ratio (HR) indicated no statistically significant difference between athletes and controls (0.84; 95% confidence interval [CI], 0.55-1.29). In subgroup analyses, adjusted HRs for athletes with recent high (>= 15 metabolic equivalent hours [MET-h]/week) and low (= 6 METs at least 75 minutes/week) had initially 77% lower hazard rate (adjusted HR 0.23; 95% CI, 0.06-0.86) than controls. However, the HR was time-dependent (adjusted HR 1.04; 95% CI, 1.01-1.07); by age 75 years the HRs for the athletes with vigorous-intensity exercise reached the level of the controls, but after 85 years the HRs for these athletes increased approximately 1.3-fold annually relative to the controls. In conclusion, these data suggest that continuation of vigorous-intensity exercise is associated with lower HR of hip fracture up to old age. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

Radioactive decays at limits of nuclear stability

The last decades brought an impressive progress in synthesizing and studying properties of nuclides located very far from the beta stability line. Among the most fundamental properties of such exotic nuclides, usually established first, is the half-life, possible radioactive decay modes, and their relative probabilities. When approaching limits of nuclear stability, new decay modes set in. First, beta decays become accompanied by emission of nucleons from highly excited states of daughter nuclei. Second, when the nucleon separation energy becomes negative, nucleons start to be emitted from the ground state. Here, we present a review of the decay modes occurring close to the limits of stability. The experimental methods used to produce, identify and detect new species and their radiation are discussed. The current theoretical understanding of these decay processes is overviewed. The theoretical description of the most recently discovered and most complex radioactive process - the two-proton radioactivity - is discussed in more detail.Comment: Review, 68 pages, 39 figure

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms

Demographically adjusted Rey-Osterrieth Complex Figure Test norms in a Swedish and Norwegian cohort aged 49-77?years and comparison with North American norms

Introduction: The Rey–Osterrieth Complex Figure Test (RCFT) is one of the most commonly used neuropsychological tests in Sweden and Norway. However, no publications provide normative data for this population. The objective of this study was to present demographically adjusted norms for a Swedish and Norwegian population and to evaluate these in an independent comparison group. Methods: The RCFT was administrated to 344 healthy controls recruited from the Swedish Gothenburg MCI study, the Norwegian Dementia Disease Initiation study, and the Swedish Cardiopulmonary Bioimage Study. Age ranged from 49 to 77 years (mean = 62.4 years, SD = 5.0 years), and education ranged from 6 to 24 years (mean = 13.3 years, SD = 3.0 years). Using a regression-based procedure, we investigated the effects of age, sex, and years of education on test performance. We compared and evaluated our Swedish and Norwegian norms with North American norms in an independent comparison group of 145 individuals. Results: In healthy controls, age and education were associated with performance on the RCFT. When comparing normative RCFT performance in an independent comparison group, North American norms generally overestimated immediate and delayed recall performance. In contrast, our Swedish and Norwegian norms appear to better take into account factors of age and education. Conclusions: We presented demographically adjusted norms for the RCFT in a Swedish and Norwegian sample. This is the first normative study of the RCFT that presents normative data for this population. In addition, we showed that North American norms might produce inaccurate normative estimations in an independent comparison group

A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign

Background PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g. desmoplakin (DSP). PPK should trigger genetic testing to reveal mutations with possible related cardiac disease. Objectives To report a large multigenerational family with a novel DSP mutation associated with early-onset PPK and adult-onset cardiomyopathy and arrhythmias. Methods A custom-designed in-house panel of 35 PPK related genes was used to screen mutations in the index patient with focal PPK. The identified DSP mutation was verified by Sanger sequencing. DNA samples from 20 members of the large multigenerational family were sequenced for the DSP mutation. Medical records were reviewed. Clinical dermatological evaluation was performed, including light microscopy of hair samples. Cardiac evaluation included clinical examination, echocardiography, cardiac magnetic resonance imaging (CMR), electrocardiogram (ECG), Holter monitoring and laboratory tests. Results We identified a novel autosomal dominant truncating DSP c.2493delA p.(Glu831Aspfs*33) mutation associated with dilated cardiomyopathy (DCM) with arrhythmia susceptibility and focal PPK as an early cutaneous sign. The mutation was found in nine affected family members, but not in any unaffected members. Onset of dermatological findings preceded cardiac symptoms which were variable and occurred at adult age. Conclusions We report a novel truncating DSP mutation causing focal PPK with varying severity and left ventricular dilatation and ventricular extrasystoles. This finding emphasizes the importance of genetic diagnosis in patients with PPK for clinical counselling and management of cardiomyopathies and arrhythmias.Peer reviewe

Metabolic profiling of angiopoietin-like protein 3 and 4 inhibition: a drug-target Mendelian randomization analysis

AIMS : Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) inhibit lipoprotein lipase (LPL) and represent emerging drug targets to lower circulating triglycerides and reduce cardiovascular risk. To investigate the molecular effects of genetic mimicry of ANGPTL3 and ANGPTL4 inhibition and compare them to the effects of genetic mimicry of LPL enhancement. METHODS AND RESULTS : Associations of genetic variants in ANGPTL3 (rs11207977-T), ANGPTL4 (rs116843064-A), and LPL (rs115849089-A) with an extensive serum lipid and metabolite profile (208 measures) were characterized in six cohorts of up to 61 240 participants. Genetic associations with anthropometric measures, glucose-insulin metabolism, blood pressure, markers of kidney function, and cardiometabolic endpoints via genome-wide summary data were also explored. ANGPTL4 rs116843064-A and LPL rs115849089-A displayed a strikingly similar pattern of associations across the lipoprotein and lipid measures. However, the corresponding associations with ANGPTL3 rs11207977-T differed, including those for low-density lipoprotein and high-density lipoprotein particle concentrations and compositions. All three genotypes associated with lower concentrations of an inflammatory biomarker glycoprotein acetyls and genetic mimicry of ANGPTL3 inhibition and LPL enhancement were also associated with lower C-reactive protein. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower waist-to-hip ratio, improved insulin-glucose metabolism, and lower risk of coronary heart disease and type 2 diabetes, whilst genetic mimicry of ANGPTL3 was associated with improved kidney function. CONCLUSIONS : Genetic mimicry of ANGPTL4 inhibition and LPL enhancement have very similar systemic metabolic effects, whereas genetic mimicry of ANGPTL3 inhibition showed differing metabolic effects, suggesting potential involvement of pathways independent of LPL. Genetic mimicry of ANGPTL4 inhibition and LPL enhancement were associated with a lower risk of coronary heart disease and type 2 diabetes. These findings reinforce evidence that enhancing LPL activity (either directly or via upstream effects) through pharmacological approaches is likely to yield benefits to human health

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases