Which factors are associated with quality of life in patients with Graves' orbitopathy presenting for orbital decompression surgery?

Purpose: Graves’ orbitopathy (GO) is associated with changes in the appearance of the eyes and visual dysfunction. Patients report feeling socially isolated and unable to continue with day-to-day activities. This study aimed at investigating the demographic, clinical, and psychosocial factors associated with quality of life in patients presenting for orbital decompression surgery. Methods: One-hundred and twenty-three adults with GO due for orbital decompression at Moorfields Eye Hospital London were recruited prospectively. Clinical measures including treatment history, exophthalmos, optic neuropathy, and diplopia were taken by an ophthalmologist. Participants completed psychosocial questionnaires, including the Graves’ Ophthalmopathy Quality of Life Scale (GO-QOL), the Hospital Anxiety and Depression Scale, and the Derriford Appearance Scale. Hierarchical multiple regression analyses were used to identify predictors of quality of life. Results: Higher levels of potential cases of clinical anxiety (37%) and depression (26%) were found in this study sample than in patients with other chronic diseases or facial disfigurements. A total of 55% of the variance in GO-QOL visual function scores was explained by the regression model; age, asymmetrical GO and depressed mood were significant unique contributors. In all, 75% of the variance in GO-QOL appearance scores was explained by the regression model; gender, appearance-related cognitions and depressed mood were significant unique contributors. Conclusion: Appearance-related quality of life and mood were particularly affected in this sample. Predominantly psychosocial characteristics were associated with quality of life. It is important when planning surgery for patients that clinicians be aware of factors that could potentially influence outcomes

Fracture model with variable range of interaction

We introduce a fiber bundle model where the interaction among fibers is modeled by an adjustable stress-transfer function which can interpolate between the two limiting cases of load redistribution, the global and the local load sharing schemes. By varying the range of interaction several features of the model are numerically studied and a crossover from mean field to short range behavior is obtained. The properties of the two regimes and the emergence of the crossover in between are explored by numerically studying the dependence of the ultimate strength of the material on the system size, the distribution of avalanches of breakings, and of the cluster sizes of broken fibers. Finally, we analyze the moments of the cluster size distributions to accurately determine the value at which the crossover is observed.Comment: 8 pages, 8 figures. Two columns revtex format. Final version to be published in Phys. Rev.

Ising models on power-law random graphs

We study a ferromagnetic Ising model on random graphs with a power-law degree distribution and compute the thermodynamic limit of the pressure when the mean degree is finite (degree exponent $\tau>2$), for which the random graph has a tree-like structure. For this, we adapt and simplify an analysis by Dembo and Montanari, which assumes finite variance degrees ($\tau>3$). We further identify the thermodynamic limits of various physical quantities, such as the magnetization and the internal energy

Time evolution of damage under variable ranges of load transfer

We study the time evolution of damage in a fiber bundle model in which the range of interaction of fibers varies through an adjustable stress transfer function recently introduced. We find that the lifetime of the material exhibits a crossover from mean field to short range behavior as in the static case. Numerical calculations showed that the value at which the transition takes place depends on the system's disorder. Finally, we have performed a microscopic analysis of the failure process. Our results confirm that the growth dynamics of the largest crack is radically different in the two limiting regimes of load transfer during the first stages of breaking.Comment: 8 pages, 7 figures, revtex4 styl

Autoimmunity and effector recognition in Arabidopsis thaliana can be uncoupled by mutations in the RRS1‐R immune receptor

Plant nucleotide-binding leucine-rich repeat (NLR) disease resistance proteins recognize specific pathogen effectors and activate a cellular defense program. In Arabidopsis thaliana (Arabidopsis), Resistance to Ralstonia solanacearum 1 (RRS1-R) and Resistance to Pseudomonas syringae 4 (RPS4) function together to recognize the unrelated bacterial effectors PopP2 and AvrRps4. In the plant cell nucleus, the RRS1-R/RPS4 complex binds to and signals the presence of AvrRps4 or PopP2. The exact mechanism underlying NLR signaling and immunity activation remains to be elucidated. Using genetic and biochemical approaches, we characterized the intragenic suppressors of sensitive to low humidity 1 (slh1), a temperature-sensitive autoimmune allele of RRS1-R. Our analyses identified five amino acid residues that contribute to RRS1-R SLH 1 autoactivity. We investigated the role of these residues in the RRS1-R allele by genetic complementation, and found that C15 in the Toll/interleukin-1 receptor (TIR) domain and L816 in the LRR domain were also important for effector recognition. Further characterization of the intragenic suppressive mutations located in the RRS1-R TIR domain revealed differing requirements for RRS1-R/RPS4-dependent autoimmunity and effector-triggered immunity. Our results provide novel information about the mechanisms which, in turn, hold an NLR protein complex inactive and allow adequate activation in the presence of pathogens

Further Evidence for Intrinsic Redshifts in Normal Spiral Galaxies

Evidence from galaxy absolute magnitudes, linear diameters, and HyperLeda images is presented which strongly supports the interpretation that some normal spiral galaxies can contain large non-cosmological (intrinsic) redshifts in excess of 5000 km s-1.Comment: 17 pages, Astrophysics&Space Science - Accepted for publicatio

Dynamics of systems with isotropic competing interactions in an external field: a Langevin approach

We study the Langevin dynamics of a ferromagnetic Ginzburg-Landau Hamiltonian with a competing long-range repulsive term in the presence of an external magnetic field. The model is analytically solved within the self consistent Hartree approximation for two different initial conditions: disordered or zero field cooled (ZFC), and fully magnetized or field cooled (FC). To test the predictions of the approximation we develop a suitable numerical scheme to ensure the isotropic nature of the interactions. Both the analytical approach and the numerical simulations of two-dimensional finite systems confirm a simple aging scenario at zero temperature and zero field. At zero temperature a critical field $h_c$ is found below which the initial conditions are relevant for the long time dynamics of the system. For $h < h_c$ a logarithmic growth of modulated domains is found in the numerical simulations but this behavior is not captured by the analytical approach which predicts a $t^1/2$ growth law at $T = 0$

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Purpose: Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. Methods: We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Results: Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. Conclusions: HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of ‘immune cold’ TNBCs

Interventions for promoting physical activity in people with neuromuscular disease

BACKGROUND: The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health conditions, international guidance advises being as physically active as possible. Evidence from community interventions of physical activity indicate that people living with medical conditions are sometimes excluded from participation in studies. In this review, we considered the effects of activity-promoting interventions on physical activity and well-being in studies, as well as any adverse events experienced by participants living with inherited or acquired neuromuscular diseases (NMDs).  OBJECTIVES: To assess the effects of interventions designed to promote physical activity in people with NMD compared with no intervention or alternative interventions. SEARCH METHODS: On 30 April 2020, we searched Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, and ClinicalTrials.Gov. WHO ICTRP was not accessible at the time. SELECTION CRITERIA: We considered randomised or quasi-randomised trials, including cross-over trials, of interventions designed to promote physical activity in people with NMD compared to no intervention or alternative interventions. We specifically included studies that reported physical activity as an outcome measure. Our main focus was studies in which promoting physical activity was a stated aim but we also included studies in which physical activity was assessed as a secondary or exploratory outcome. DATA COLLECTION AND ANALYSIS: We used standard Cochrane procedures. MAIN RESULTS: The review included 13 studies (795 randomised participants from 12 studies; number of participants unclear in one study) of different interventions to promote physical activity. Most studies randomised a minority of invited participants. No study involved children or adolescents and nine studies reported minimal entry criteria for walking. Participants had one of nine inherited or acquired NMDs. Types of intervention included structured physical activity support, exercise support (as a specific form of physical activity), and behaviour change support that included physical activity or exercise. Only one included study clearly reported that the aim of intervention was to increase physical activity. Other studies reported or planned to analyse the effects of intervention on physical activity as a secondary or exploratory outcome measure. Six studies did not report results for physical activity outcomes, or the data were not usable. We judged 10 of the 13 included studies at high or unclear risk of bias from incomplete physical activity outcome reporting. We did not perform a meta-analysis for any comparison because of differences in interventions and in usual care. We also found considerable variation in how studies reported physical activity as an outcome measure. The studies that reported physical activity measurement did not always clearly report intention-to-treat (ITT) analysis or whether final assessments occurred during or after intervention. Based on prespecified measures, we included three comparisons in our summary of findings. A physical activity programme (weight-bearing) compared to no physical activity programme One study involved adults with diabetic peripheral neuropathy (DPN) and reported weekly duration of walking during and at the end of a one-year intervention using a StepWatch ankle accelerometer. Based on the point estimate and low-certainty evidence, intervention may have led to an important increase in physical activity per week; however, the 95% confidence interval (CI) included the possibility of no difference or an effect in either direction at three months (mean difference (MD) 34 minutes per week, 95% CI -92.19 to 160.19; 69 participants), six months (MD 68 minutes per week, 95% CI -55.35 to 191.35; 74 participants), and 12 months (MD 49 minutes per week, 95% CI -75.73 to 173.73; 70 participants). Study-reported effect estimates for foot lesions and full-thickness ulcers also included the possibility of no difference, a higher, or lower risk with intervention. A sensor-based, interactive exercise programme compared to no sensor-based, interactive exercise programme One study involved adults with DPN and reported duration of walking over 48 hours at the end of four weeks' intervention using a t-shirt embedded PAMSys sensor. It was not possible to draw conclusions about the effectiveness of the intervention from the very low-certainty evidence (MD -0.64 hours per 48 hours, 95% CI -2.42 to 1.13; 25 participants). We were also unable to draw conclusions about impact on the Physical Component Score (PCS) for quality of life (MD 0.24 points, 95% CI -5.98 to 6.46; 35 participants; very low-certainty evidence), although intervention may have made little or no difference to the Mental Component Score (MCS) for quality of life (MD 5.10 points, 95% CI -0.58 to 10.78; 35 participants; low-certainty evidence). A functional exercise programme compared to a stretching exercise programme One study involved adults with spinal and bulbar muscular atrophy and reported a daily physical activity count at the end of 12 weeks' intervention using an Actical accelerometer. It was not possible to draw conclusions about the effectiveness of either intervention (requiring compliance) due to low-certainty evidence and unconfirmed measurement units (MD -8701, 95% CI -38,293.30 to 20,891.30; 43 participants). Functional exercise may have made little or no difference to quality of life compared to stretching (PCS: MD -1.10 points, 95% CI -5.22 to 3.02; MCS: MD -1.10 points, 95% CI -6.79 to 4.59; 49 participants; low-certainty evidence). Although studies reported adverse events incompletely, we found no evidence of supported activity increasing the risk of serious adverse events. AUTHORS' CONCLUSIONS: We found a lack of evidence relating to children, adolescents, and non-ambulant people of any age. Many people living with NMD did not meet randomised controlled trial eligibility criteria. There was variation in the components of supported activity intervention and usual care, such as physical therapy provision. We identified variation among studies in how physical activity was monitored, analysed, and reported. We remain uncertain of the effectiveness of promotional intervention for physical activity and its impact on quality of life and adverse events. More information is needed on the ITT population, as well as more complete reporting of outcomes. While there may be no single objective measure of physical activity, the study of qualitative and dichotomous change in self-reported overall physical activity might offer a pragmatic approach to capturing important change at an individual and population level

Epidemic centrality - is there an underestimated epidemic impact of network peripheral nodes?

In the study of disease spreading on empirical complex networks in SIR model, initially infected nodes can be ranked according to some measure of their epidemic impact. The highest ranked nodes, also referred to as "superspreaders", are associated to dominant epidemic risks and therefore deserve special attention. In simulations on studied empirical complex networks, it is shown that the ranking depends on the dynamical regime of the disease spreading. A possible mechanism leading to this dependence is illustrated in an analytically tractable example. In systems where the allocation of resources to counter disease spreading to individual nodes is based on their ranking, the dynamical regime of disease spreading is frequently not known before the outbreak of the disease. Therefore, we introduce a quantity called epidemic centrality as an average over all relevant regimes of disease spreading as a basis of the ranking. A recently introduced concept of phase diagram of epidemic spreading is used as a framework in which several types of averaging are studied. The epidemic centrality is compared to structural properties of nodes such as node degree, k-cores and betweenness. There is a growing trend of epidemic centrality with degree and k-cores values, but the variation of epidemic centrality is much smaller than the variation of degree or k-cores value. It is found that the epidemic centrality of the structurally peripheral nodes is of the same order of magnitude as the epidemic centrality of the structurally central nodes. The implications of these findings for the distributions of resources to counter disease spreading are discussed