The development and initial validation of the Breast Cancer Recurrence instrument (BreastCaRe)—a patient-reported outcome measure for detecting symptoms of recurrence after breast cancer

Purpose: Patient-reported outomes (PRO) may facilitate prompt treatment. We describe the development and psychometric properties of the first instrument to monitor for symptoms of breast cancer (BC) recurrence. Methods: This study is nested in the MyHealth randomized trial of nurse-led follow-up based on electronically-collected PROs. We constructed items assessing symptoms of potential recurrence through expert interviews with six BC specialists in Denmark. Semi-structured cognitive interviews were carried out with a patient panel to assess acceptability and comprehensibility. Items were subsequently tested in a population of 1170 women 1–10 years after completing BC treatment. We carried out multiple-groups confirmatory factor analysis (CFA) and Rasch analysis to test dimensionality, local dependence (LD) and differential item functioning (DIF) according to sociodemographic and treatment-related factors. Clinical data was obtained from the Danish Breast Cancer Group registry. Results: Twenty-two items were generated for the Breast Cancer Recurrence instrument (BreastCaRe). Cognitive testing resulted in clearer items. Seven subscales based on general, bone, liver, lung, brain, locoregional and contralateral recurrence symptoms were proposed. Both CFA and Rasch models confirmed the factor structure. No DIF was identified. Five item pairs showed LD but all items were retained to avoid loss of clinical information. Rasch models taking LD into account were used to generate a standardized scoring table for each subscale. Conclusions: The BreastCaRe has good content and structural validity, patient acceptability and measurement invariance. We are preparing to examine the predictive validity of this new instrument

Large Scale Structure Formation with Global Topological Defects. A new Formalism and its implementation by numerical simulations

We investigate cosmological structure formation seeded by topological defects which may form during a phase transition in the early universe. First we derive a partially new, local and gauge invariant system of perturbation equations to treat microwave background and dark matter fluctuations induced by topological defects or any other type of seeds. We then show that this system is well suited for numerical analysis of structure formation by applying it to seeds induced by fluctuations of a global scalar field. Our numerical results are complementary to previous investigations since we use substantially different methods. The resulting microwave background fluctuations are compatible with older simulations. We also obtain a scale invariant spectrum of fluctuations with about the same amplitude. However, our dark matter results yield a smaller bias parameter compatible with $b\sim 2$ on a scale of $20 Mpc$ in contrast to previous work which yielded to large bias factors. Our conclusions are thus more positive. According to the aspects analyzed in this work, global topological defect induced fluctuations yield viable scenarios of structure formation and do better than standard CDM on large scales.Comment: uuencoded, compressed tar-file containing the text in LaTeX and 12 Postscript Figures, 41 page

Double Inflation in Supergravity and the Large Scale Structure

The cosmological implication of a double inflation model with hybrid + new inflations in supergravity is studied. The hybrid inflation drives an inflaton for new inflation close to the origin through supergravity effects and new inflation naturally occurs. If the total e-fold number of new inflation is smaller than $\sim 60$, both inflations produce cosmologically relevant density fluctuations. Both cluster abundances and galaxy distributions provide strong constraints on the parameters in the double inflation model assuming $\Omega_0=1$ standard cold dark matter scenario. The future satellite experiments to measure the angular power spectrum of the cosmic microwave background will make a precise determination of the model parameters possible.Comment: 19 pages (RevTeX file

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

Measurement of Bottom versus Charm as a Function of Transverse Momentum with Electron-Hadron Correlations in p+p Collisions at sqrt(s)=200 GeV

The momentum distribution of electrons from semi-leptonic decays of charm and bottom for mid-rapidity |y|<0.35 in p+p collisions at sqrt(s)=200 GeV is measured by the PHENIX experiment at the Relativistic Heavy Ion Collider (RHIC) over the transverse momentum range 2 < p_T < 7 GeV/c. The ratio of the yield of electrons from bottom to that from charm is presented. The ratio is determined using partial D/D^bar --> e^{+/-} K^{-/+} X (K unidentified) reconstruction. It is found that the yield of electrons from bottom becomes significant above 4 GeV/c in p_T. A fixed-order-plus-next-to-leading-log (FONLL) perturbative quantum chromodynamics (pQCD) calculation agrees with the data within the theoretical and experimental uncertainties. The extracted total bottom production cross section at this energy is \sigma_{b\b^bar}= 3.2 ^{+1.2}_{-1.1}(stat) ^{+1.4}_{-1.3}(syst) micro b.Comment: 432 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cosmological constraints from galaxy clustering

In this manuscript I review the mathematics and physics that underpins recent work using the clustering of galaxies to derive cosmological model constraints. I start by describing the basic concepts, and gradually move on to some of the complexities involved in analysing galaxy redshift surveys, focusing on the 2dF Galaxy Redshift Survey (2dFGRS) and the Sloan Digital Sky survey (SDSS). Difficulties within such an analysis, particularly dealing with redshift space distortions and galaxy bias are highlighted. I then describe current observations of the CMB fluctuation power spectrum, and consider the importance of measurements of the clustering of galaxies in light of recent experiments. Finally, I provide an example joint analysis of the latest CMB and large-scale structure data, leading to a set of parameter constraints.Comment: 30 pages, 13 figures. Lecture given at Third Aegean Summer School, The invisible universe: Dark matter and Dark energ

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Parental origin of sequence variants associated with complex diseases

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldEffects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.info:eu-repo/grantAgreement/EC/FP7/21807

Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: An observational cohort study

Objectives To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020. Design Observational cohort study. Setting COVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA. Participants There were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort. Primary and secondary outcome measures Incident acute clinical outcomes, including in-hospital all-cause mortality. Results Respectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50- 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by -0.036 per month (95% CI -0.042 to -0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI -0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were -0.024 (95% CI -0.032 to -0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort. Conclusion The incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes