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We generated Optical Coherence Tomography (OCT) data of much higher resolution than usual on retinal nerve fiber layer (RNFL) thickness of a given eye. These consist of measurements made at hundreds of angular-points defined on a circular coordinate system. Traditional analysis of OCT RNFL data does not utilize insightful characteristics such as its circularity and granularity for common downstream applications. To address this, we present a new circular statistical framework that defines an Angular Decay function and thereby provides a directionally precise representation of an eye with attention to patterns of focused RNFL loss. By applying to a clinical cohort of Asian Indian eyes, the generated circular data were modeled with a finite mixture of von Mises distributions, which led to an unsupervised identification in different age-groups of recurrent clusters of glaucomatous eyes with distinct directional signatures of RNFL decay. New indices of global and local RNFL loss were computed for comparing the structural differences between these glaucoma clusters across the age-groups and improving classification. Further, we built a catalog of directionally precise statistical distributions of RNFL thickness for the said population of normal eyes as stratified by their age and optic disc size.

Background: The management of chronic thoracic aortic aneurysms includes conservative management, watchful waiting, endovascular stent grafting and open surgical replacement. The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) study investigates timing and intervention choice. Objective: To describe pre- and post-intervention management of and outcomes for chronic thoracic aortic aneurysms. Design: A systematic review of intervention effects; a Delphi study of 360 case scenarios based on aneurysm size, location, age, operative risk and connective tissue disorders; and a prospective cohort study of growth, clinical outcomes, costs and quality of life. Setting: Thirty NHS vascular/cardiothoracic units. Participants: Patients aged > 17 years who had existing or new aneurysms of ≥ 4 cm in diameter in the arch, descending or thoracoabdominal aorta. Interventions: Endovascular stent grafting and open surgical replacement. Main outcomes: Pre-intervention aneurysm growth, pre-/post-intervention survival, clinical events, readmissions and quality of life; and descriptive statistics for costs and quality-adjusted life-years over 12 months and value of information using a propensity score-matched subsample. Results: The review identified five comparative cohort studies (endovascular stent grafting patients, n = 3955; open surgical replacement patients, n = 21,197). Pooled short-term all-cause mortality favoured endovascular stent grafting (odds ratio 0.71, 95% confidence interval 0.51 to 0.98; no heterogeneity). Data on survival beyond 30 days were mixed. Fewer short-term complications were reported with endovascular stent grafting. The Delphi study included 20 experts (13 centres). For patients with aneurysms of ≤ 6.0 cm in diameter, watchful waiting was preferred. For patients with aneurysms of > 6.0 cm, open surgical replacement was preferred in the arch, except for elderly or high-risk patients, and in the descending aorta if patients had connective tissue disorders. Otherwise endovascular stent grafting was preferred. Between 2014 and 2018, 886 patients were recruited (watchful waiting, n = 489; conservative management, n = 112; endovascular stent grafting, n = 150; open surgical replacement, n = 135). Pre-intervention death rate was 8.6% per patient-year; 49.6% of deaths were aneurysm related. Death rates were higher for women (hazard ratio 1.79, 95% confidence interval 1.25 to 2.57; p = 0.001) and older patients (age 61–70 years: hazard ratio 2.50, 95% confidence interval 0.76 to 5.43; age 71–80 years: hazard ratio 3.49, 95% confidence interval 1.26 to 9.66; age > 80 years: hazard ratio 7.01, 95% confidence interval 2.50 to 19.62; all compared with age 6 cm) aneurysms require intervention without delay. Endovascular stent grafting and open surgical replacement were successful for carefully selected patients, but cost comparisons were unfeasible. The choice of intervention is well established, but the timing of intervention remains challenging. Future work: Further research should include an analysis of the risk factors for growth/rupture and long-term outcomes. Trial registration: Current Controlled Trials ISRCTN04044627 and NCT02010892. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 6. See the NIHR Journals Library website for further project information.

Objectives The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.Design A prospective online three-part longitudinal survey.Setting Acute hospitals in the UK and Ireland.Participants Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measures Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.Results The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).Conclusion Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration number ISRCTN10666798.

Plant species around the world are negatively affected by habitat fragmentation and climate change. Montane willow populations in the UK have declined primarily due to grazing, as well as climate change and muirburn in certain areas. Only small, isolated populations remain, scattered across steep ledges where shrubs escape most grazing animals. We explored the genetic effects of habitat fragmentation on gene flow and genetic diversity in the largest remaining patches in the UK, which lie in Scotland, for two now restricted and rare montane willow species— Salix myrsinites and Salix lapponum . Using ten microsatellite loci and an almost complete genetic inventory in the central Cairngorms area ( S. myrsinites n = 186, S. lapponum n = 91) we showed that genetic diversity (heterozygosity and allelic richness) is relatively high in both species, particularly high for the decaploid S. myrsinites , and clonal reproduction low. Historic gene flow between populations could be demonstrated. Significant inbreeding was detected in both species and observed seed set and numbers of juveniles in the field are low, possibly indicating signs of inbreeding depression. Both species have extremely low numbers of individuals at each site, with many being smaller than ten, and in some cases combined with skewed sex-ratios (mainly female biased). This will likely cause more severe reproductive failures in the next generations unless population numbers are increased. Reinforcing populations of both species under low grazing pressure with new, unrelated individuals, as well as creating new stepping-stone populations will be necessary to help the recovery of these species. Results from this study will inform restoration work in Scotland aiming to create continuous woodland habitats from pinewoods at lower altitudes through to higher altitude downy birch woodlands merging with montane willows.

Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA.Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed.Results: CD14++CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro, RA serum promoted differentiation of CD14+CD16− to CD14++CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells.Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.

Objective: Determine the impact of the COVID-19 pandemic on the changes in training, sleep, diet, and mental health of cross-country runners. Participants: Cross-country runners from NCAA Division II institutes. Methods: Wilcoxon signed-rank test was performed to analyze survey responses to ordinal questions on the survey while Spearman's rank correlation analysis (?) was used to calculate correlation between after the start of pandemic questions. Data was marked significant at p < 0.05. Results: Analysis of the survey responses revealed that cross-country runners were more likely to experience feelings of depression (p < 0.001), lack of motivation (p < 0.001), and higher daily stress (p < 0.001) after the start of the pandemic. After the start of the pandemic, runners running less days per week were more likely to report an increased feeling of depression (?=-0.315, p = 0.008) and lack of motivation (?=-0.458, p < 0.001). Conclusions: The present study underscores the importance of training, sleep, diet, and mental health amongst cross-country runners.

Past research aimed at service recovery has focused on actions that are taken to retain customers, and the possibility of overcoming the mistakes of service delivery, though the multidimensional nature of the service recovery process has begun to move beyond the complaint handling process. In this paper, we identify the most important issues addressed in service recovery and present a framework for addressing them. We used an extensive integrative review methodology. Between 1988 and 2017 the number of articles in these journals was kept between 26 and 30. The majority took a business perspective to study services recovery, while a minority took an inter-disciplinarity perspective. The study’s findings are expected to provide insights into the antecedents and consequences of service recovery performance, particularly how job resources and demands influence employee burnout and work engagement, which in turn affect service recovery performance and customer perceptions of justice. The research aims to contribute to the discourse on service recovery by building a multi-level model that explains the service recovery performance of frontline employees and the impact of the service recovery system on customer justice perceptions. Thus, this research is expected to contribute to robust conclusions on the antecedents and consequences of employee service recovery performance nested within the unit-level construct, i.e., the service recovery system.

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and present challenges to clinical decision-making. We generated a dataset of Optical Coherence Tomography (OCT) based high-resolution circular measurements on NRR phenotypes, along with other clinical covariates, of 3973 healthy eyes as part of an established clinical cohort of Asian Indian participants. We introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, followed by meta-clustering to characterize the clusters using clinical covariates, and presented a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40-49 years with predictive potential for glaucoma. Our dataset also addresses the disparity of representation of this particular population in normative OCT databases.

A nonparametric test labelled 'Rao Spacing-frequencies test' is explored and developed for testing whether two circular samples come from the same population. Its exact distribution and performance relative to comparable tests such as the Wheeler-Watson test and the Dixon test in small samples, are discussed. Although this test statistic is shown to be asymptotically normal, as one would expect, this large sample distribution does not provide satisfactory approximations for small to moderate samples. Exact critical values for small samples are obtained and tables provided here, using combinatorial techniques, and asymptotic critical regions are assessed against these. For moderate sample sizes in-between i.e. when the samples are too large making combinatorial techniques computationally prohibitive but yet asymptotic regions do not provide a good approximation, we provide a simple Monte Carlo procedure that gives very accurate critical values. As is well-known, the large number of usual rank-based tests are not applicable in the context of circular data since the values of such ranks depend on the arbitrary choice of origin and the sense of rotation used (clockwise or anti-clockwise). Tests that are invariant under the group of rotations, depend on the data through the so-called 'spacing frequencies', the frequencies of one sample that fall in between the spacings (or gaps) made by the other. The Wheeler-Watson, Dixon, and the proposed Rao tests are of this form and are explicitly useful for circular data, but they also have the added advantage of being valid and useful for comparing any two samples on the real line. Our study and simulations establish the 'Rao spacing-frequencies test' as a desirable, and indeed preferable test in a wide variety of contexts for comparing two circular samples, and as a viable competitor even for data on the real line. Computational help for implementing any of these tests, is made available online "TwoCircles" R package and is part of this paper.

In a multinomial set-up with k possible outcomes, we develop estimation under a "middle censoring" paradigm, which is as defined in Jammalamadaka and Mangalam (2003). This problem has many special features because of the inter-dependent probabilities, which we explore here.

In this paper, we consider general classes of estimators based on higher-order sample spacings, called the Generalized Spacings Estimators. Such classes of estimators are obtained by minimizing the Csiszár divergence between the empirical and true distributions for various convex functions, include the “maximum spacing estimators” as well as the maximum likelihood estimators (MLEs) as special cases, and are especially useful when the latter do not exist. These results generalize several earlier studies on spacings-based estimation, by utilizing non-overlapping spacings that are of an order which increases with the sample size. These estimators are shown to be consistent as well as asymptotically normal under a fairly general set of regularity conditions. When the step size and the number of spacings grow with the sample size, an asymptotically efficient class of estimators, called the “Minimum Power Divergence Estimators,” are shown to exist. Simulation studies give further support to the performance of these asymptotically efficient estimators in finite samples and compare well relative to the MLEs. Unlike the MLEs, some of these estimators are also shown to be quite robust under heavy contamination.