Direct strain and elastic energy evaluation in rolled-up semiconductor tubes by x-ray micro-diffraction

We depict the use of x-ray diffraction as a tool to directly probe the strain status in rolled-up semiconductor tubes. By employing continuum elasticity theory and a simple model we are able to simulate quantitatively the strain relaxation in perfect crystalline III-V semiconductor bi- and multilayers as well as in rolled-up layers with dislocations. The reduction in the local elastic energy is evaluated for each case. Limitations of the technique and theoretical model are discussed in detail.Comment: 32 pages (single column), 9 figures, 39 reference

The distinctive signatures of promoter regions and operon junctions across prokaryotes

Here we show that regions upstream of first transcribed genes have oligonucleotide signatures that distinguish them from regions upstream of genes in the middle of operons. Databases of experimentally confirmed transcription units do not exist for most genomes. Thus, to expand the analyses into genomes with no experimentally confirmed data, we used genes conserved adjacent in evolutionarily distant genomes as representatives of genes inside operons. Likewise, we used divergently transcribed genes as representative examples of first transcribed genes. In model organisms, the trinucleotide signatures of regions upstream of these representative genes allow for operon predictions with accuracies close to those obtained with known operon data (0.8). Signature-based operon predictions have more similar phylogenetic profiles and higher proportions of genes in the same pathways than predicted transcription unit boundaries (TUBs). These results confirm that we are separating genes with related functions, as expected for operons, from genes not necessarily related, as expected for genes in different transcription units. We also test the quality of the predictions using microarray data in six genomes and show that the signature-predicted operons tend to have high correlations of expression. Oligonucleotide signatures should expand the number of tools available to identify operons even in poorly characterized genomes

EFFECT OF POST-EXERCISE COLD WATER IMMERSION ON MOLECULAR RESPONSES TO HIGH-INTENSITY INTERMITTENT EXERCISE

The balance between the stress of training and competition and sufficient recovery is critical within the development of athletic performance. This stems from the need to recover between successive intense periods of exercise and provide sufficient time through which to adapt to the prescribed training stimulus. Cold water immersion (CWI) is now widely used by athletes to enhance the rate of recovery following training and competition. However, little information currently exists with respect to its influence on skeletal muscle adaptation. Therefore, the aim of this thesis was to investigate the impact of CWI on acute markers of adaptation in human skeletal muscle following low-damaging high-intensity intermittent exercise.The aim of study 1 (Chapter 4) was to devise a low-damaging high-intensity intermittent running protocol which would be used as the criterion mode of exercise in future studies within the thesis. The exercise was comprised of 60-min of high-intensity intermittent exercise (8 × 3-min bouts at 90% V ̇O2max interspersed with 3-min recovery) on a motorised treadmill. No significant reduction in maximal voluntary contraction of the quadriceps was observed immediately following completion of the exercise protocol or during the subsequent 7 d period compared to pre-exercise values (P = 0.59). Creatine Kinase (CK) concentrations remained similar to baseline following exercise (P = 0.96). Myoglobin (Mb) content increased following exercise (P = 0.01). However, values returned to baseline after 24 h (P = 0.32). These results suggest the high-intensity intermittent running protocol induced changes in physiological and subjective indices consistent with the effects of low muscle damaging as opposed to those changes normally associated with exercise-induced severe muscle damage.The purpose of the second study (Chapter 5) was to examine the effects of CWI (2 × 5-min (8oC)) on acute markers of skeletal muscle adaptation at rest. Rectal temperature remained similar throughout the CWI protocol (P = 0.36). However, significant reductions in skin (thigh and calf) and muscle temperature were observed immediately post-immersion and the post-immersion period (P 0.05), however, skin (thigh and calf) and muscle temperature were reduced in the CWI condition compared to Cont (P 0.05). These results indicate that increasing the repeated post-exercise CWI does not further increases the expression of upstream signalling pathways associated with mitochondrial biogenesis and angiogenesis in human skeletal muscle.This thesis provides novel findings concerning the influence of high-intensity intermittent exercise and post-exercise CWI on cellular and molecular adaptations in human skeletal muscle. These findings may offer important insights for athletes wishing to maximize training adaptations

Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

This is the final version. Available on open access from Elsevier via the DOI in this recordObjectives: This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL). Background: EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (VO2peak) or through submaximal tests, such as the 6-min walk test (6MWT). Methods: After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome. Results: Exercise-based CR is associated with positive effects on EC measured through VO2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (VO2peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R2 <52%; |ρ| < 0.72). Estimated STE was an increase of 5 ml/kg/min for VO2peak and 80 m for 6MWT to predict a significant improvement in HRQOL. Conclusions: The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.National Institute for Health Research (NIHR)University of Exete

Pseudogap in 1d revisited

Two decades ago, Sadovskii found an exact solution of a model describing a pseudogap in electron energy spectrum (first introduced by Lee, Rice and Anderson). The discovery of a pseudogap in high-Tc superconductors has revived the interest to his exact solution. I review the model with the emphasis on physical content, point out an error in the original Sadovskii's solution and explain which problem he actually solved. A recent incorporation of Sadovskii's ideas into a description of "hot spots" on the Fermi surface in cuprate superconductors (Schmalian, Pines and Stojkovic) is briefly discussed.Comment: Final version to appear in PR

Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

BACKGROUND: Real-world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies. OBJECTIVES: (i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival. METHODS: A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness. RESULTS: In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 [95% confidence interval (CI) 0·77-0·79], 0·88 (95% CI 0·86-0·91) and 0·88 (95% CI 0·87-0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of adalimumab and secukinumab compared with ustekinumab were 2·11 (95% CI 1·76-2·54) and 0·67 (95% CI 0·40-1·11), respectively. The presence of psoriatic arthritis predicted for survival in the adalimumab and secukinumab cohorts (adjHR 0·67, 95% CI 0·51-0·88 and 0·70, 95% CI 0·40-1·24, respectively), but for discontinuation in the ustekinumab cohort (adjHR 1·42, 95% CI 1·12-1·81). Previous exposure to biologic therapies predicted for discontinuation in the ustekinumab and secukinumab cohorts (adjHR 1·54, 95% CI 1·26-1·89 and 1·49, 95% CI 0·91-2·45, respectively) and for survival in the adalimumab cohort (adjHR 0·71, 95% CI 0·55-0·92). CONCLUSIONS: Secukinumab and ustekinumab have similar sustained drug survival, while adalimumab has a lower drug survival in patients with psoriasis. Psoriatic arthritis and previous biologic experience were predictors with differential effects between the biologic therapies. What is already known about this topic? There is conflicting evidence over the real-world drug survival of secukinumab in patients with psoriasis. Data from registries to date suggest that secukinumab has a lower drug survival than that reported from clinical trials. What does this study add? This study found that secukinumab and ustekinumab had similar sustained drug survival in the real world, while the drug survival of adalimumab was lower, suggesting that the real-world drug survival of secukinumab is higher than previously reported. We found that psoriatic arthritis and previous biologic experience had differential effects on drug discontinuation in the three biologic cohorts. These predictors may help patients and clinicians choose the most appropriate biologic therapy

A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real‐world populations in psoriasis

Background: Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real‐world psoriasis population. Objectives: Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real‐world populations of patients on biologic therapies for psoriasis using a standardization method. Methods: Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant‐level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C‐statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting. Results: In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C‐statistic of 0.82 [95% confidence interval (CI) 0.81–0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI &lt; 1.5 were 9.27 (95% CI −3.91–22.5) per 1000 person‐years and 0.95 (95% CI −1.98–4.15), respectively. Conclusions: Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real‐world population, but this lack of external validity does not account for the efficacy–effectiveness gap

An improved model of the Edgeworth-Kuiper debris disk

(Abridged) We access the expected EKB dust disk properties by modeling. We treat the debiased population of the known transneptunian objects (TNOs) as parent bodies and generate the dust with our collisional code. The resulting dust distributions are modified to take into account the influence of gravitational scattering and resonance trapping by planets on migrating dust grains as well as the effect of sublimation. A difficulty is that the amount and distribution of dust are largely determined by sub-kilometer-sized bodies. These are directly unobservable, and their properties cannot be accessed by collisional modeling, because objects larger than 10...60m in the present-day EKB are not in a collisional equilibrium. To place additional constraints, we use in-situ measurements of the New Horizons spacecraft within 20AU. We show that the TNO population has to have a break in the size distribution at s<70km. However, even this still leaves us with several models that all correctly reproduce a nearly constant dust impact rates in the region of giant planet orbits and do not violate the constraints from the non-detection of the EKB dust thermal emission by the COBE spacecraft. The modeled EKB dust disks, which conform to the observational constraints, can either be transport-dominated or intermediate between the transport-dominated and collision-dominated regime. The in-plane optical depth of such disks is tau(r>10AU)~10^-6 and their fractional luminosity is f_d~10^-7. Planets and sublimation are found to have little effect on dust impact fluxes and dust thermal emission. The spectral energy distribution of an EKB analog, as would be seen from 10pc distance, peaks at wavelengths of 40...50\mum at F~0.5mJy, which is less than 1% of the photospheric flux at those wavelengths. Therefore, exact EKB analogs cannot be detected with present-day instruments such as Herschel/PACS.Comment: 10 pages, 8 figures, accepted for publication in Astronomy and Astophysic

Home bitter home? Gender, living arrangements, and the exclusion from homeownership among older Europeans

Abstract Homeownership is the most important asset among the elderly in Europe, but very little is known about gender and living arrangement differences in this domain. This paper aims at exploring patterns of exclusion from homeownership among middle-aged and older Europeans from a gender perspective, and with a special focus on their household composition. The analysis is based on the fourth wave of the “Survey of Health, Aging and Retirement in Europe” and includes a sub-sample of about 56,000 individuals aged 50 or over, living in 16 European countries. We estimated a set of multinomial logit models to examine the probability of being either tenant or rent-free occupiers versus homeowners. Our findings show that women are generally more likely to be excluded from homeownership than men. Nevertheless, a closer look suggests that the gender gap in homeownership is essentially generated by compositional differences between men and women, with the most relevant factor being household type. Older women are almost as twice as likely as men to live alone, which is associated—other things being equal—with a particular low likelihood to be homeowners virtually in every European country