To examine patterns of health and symptoms associated with the initiation of adjuvant endocrine therapy (ET) for primary breast cancer treatment.
The mind-body study (MBS) observational cohort ...participants provided self-reported data on physical and mental health, ET-related symptoms, as well as depression, fatigue, and sleep obtained at enrollment (after primary treatment, prior to initiation of ET) and 6 and 12 months later. Longitudinal trajectories of outcome variables among three patient groups (no ET, aromatase inhibitor AI, or tamoxifen) were compared by using linear mixed models.
Two-thirds of the 186 women initiated ET, which was evenly split between AI and tamoxifen, and no significant differences were observed in self-reported measures among the groups at baseline or in covariate-adjusted analyses. Physical health scores were below normative levels initially and improved over time, but the AI group had a significantly lower score at 12 months (P = .05); mental health scores were within the normal range, were similar in each group, and did not change over time. The no-ET group showed either stable or declining symptom severity, whereas the ET groups often showed increased severity over time, and the AI group reported more severe musculoskeletal (P = .02), hot flash (P = .02), and cognitive problems (P = .006) at one or both of the follow-up time points compared with the no-ET group. The tamoxifen group had higher levels of hot flashes (P = .002), cognitive problems (P = .016), and bladder problems (P = .02) than the no-ET group.
Attention should be given to the increased symptom burden associated with ET, and better efforts should be made to address patient-reported outcomes.
Objective: Fatigue is a common side effect of cancer treatment, but there is considerable variability in fatigue severity and persistence among survivors. This study aimed to characterize ...longitudinal trajectories of fatigue after breast cancer treatment and to identify predictors of varying fatigue trajectories. Methods: Women (N = 191) from the Mind-Body Study completed assessments after primary treatment for early stage breast cancer and at regular follow-ups that occurred up to 6 years after treatment (M = 4.3 years). Growth mixture models were used to characterize fatigue trajectories, and demographic, medical, and biobehavioral risk factors were examined as predictors of trajectory group. Results: Five trajectories were identified, characterized as High, Recovery, Late, Low, and Very Low fatigue. The High and Recovery groups (40% of sample) evidenced elevated fatigue at posttreatment that declined in Recovery but persisted in the High group. In bivariate analyses, trajectory groups differed significantly on depressive symptoms, sleep disturbance, childhood adversity, body mass index, and the inflammatory marker soluble TNF receptor type II, which were higher in the High and/or Recovery groups. In multivariate models, depressive symptoms and childhood adversity distinguished High and Recovery from other groups. Rates of chemotherapy were higher in the Recovery than in the High or Late group, whereas rates of endocrine therapy were higher in the High than in the Recovery group. Conclusions: There are distinct longitudinal trajectories of fatigue after breast cancer treatment. Psychological factors are strongly associated with adverse fatigue trajectories, and together with treatment exposures may increase risk for cancer-related fatigue.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
The scaling of disc galaxy rotation velocity with baryonic mass (the 'baryonic Tully-Fisher' relation, BTF) has long confounded galaxy formation models. It is steeper than the M ... V super( 3) ...scaling relating halo virial masses and circular velocities and its zero-point implies that galaxies comprise a very small fraction of available baryons. Such low galaxy formation efficiencies may, in principle, be explained by winds driven by evolving stars, but the tightness of the BTF relation argues against the substantial scatter expected from such a vigorous feedback mechanism. We use the apostle/eagle simulations to show that the BTF relation is well reproduced in ...cold dark matter (CDM) simulations that match the size and number of galaxies as a function of stellar mass. In such models, galaxy rotation velocities are proportional to halo virial velocity and the steep velocity-mass dependence results from the decline in galaxy formation efficiency with decreasing halo mass needed to reconcile the CDM halo mass function with the galaxy luminosity function. The scatter in the simulated BTF is smaller than observed, even when considering all simulated galaxies and not just rotationally supported ones. The simulations predict that the BTF should become increasingly steep at the faint end, although the velocity scatter at fixed mass should remain small. Observed galaxies with rotation speeds below ~40 km s super( -1) seem to deviate from this prediction. We discuss observational biases and modelling uncertainties that may help to explain this disagreement in the context of ...CDM models of dwarf galaxy formation. (ProQuest: ... denotes formulae/symbols omitted.)
Polarized radio emission from PSR J1745−2900 has already been used to investigate the strength of the magnetic field in the Galactic center (GC), close to Sagittarius A*. Here we report how ...persistent radio emission from this magnetar, for over four years since its discovery, has revealed large changes in the observed Faraday rotation measure (RM), by up to 3500 rad m−2 (a 5% fractional change). From simultaneous analysis of the dispersion measure, we determine that these fluctuations are dominated by variations in either the projected magnetic field or the free electron content within the GC, along the changing line of sight to the rapidly moving magnetar. From a structure function analysis of RM variations, and a recent epoch of rapid change of RM, we determine a minimum scale of magneto-ionic fluctuations of size ∼2 au at the GC distance, inferring PSR J1745−2900 is just ∼0.1 pc behind an additional scattering screen.
In 1997, we initiated a cohort study to evaluate quality of life (QOL) and reproductive health outcomes in younger female breast cancer survivors.
Using listings from two tumor registries, we ...recruited women with stage 0, I, or II breast cancer who were 50 years or younger at diagnosis and were also disease-free survivors for 2 to 10 years. A mailed survey questionnaire assessed medical and demographic factors, health-related QOL, mood, outlook on life, and reproductive health outcomes.
We recruited 577 women, who ranged in age from 30 to 61.6 years (mean, 49.5 years) and were surveyed approximately 6 years after diagnosis. Almost three fourths had received some form of adjuvant therapy. Amenorrhea occurred frequently as a result of treatment in women > or = 40 years at diagnosis, and treatment-associated menopause was associated with poorer health perceptions. Across the cohort, physical functioning was quite good, but the youngest women experienced poorer mental health (P =.0002) and less vitality (energy; P =.03). Multiple regression analyses predicting QOL demonstrated better outcomes in African-American women, married or partnered women, and women with better emotional and physical functioning, whereas women who reported greater vulnerability had poorer QOL.
Overall QOL in younger women who survive breast cancer is good, but there is evidence of increased emotional disruption, especially among the youngest women. Factors that may contribute to poorer health perceptions and QOL include experiencing a menopausal transition as part of therapy, and feeling more vulnerable after cancer.
The Tully-Fisher relation (TFR) links the stellar mass of a disc galaxy, M sub( str), to its rotation speed: it is well approximated by a power law, shows little scatter, and evolves weakly with ...redshift. The relation has been interpreted as reflecting the mass-velocity scaling (M ... V super( 3)) of dark matter haloes, but this interpretation has been called into question by abundance-matching (AM) models, which predict the galaxy-halo mass relation to deviate substantially from a single power law and to evolve rapidly with redshift. We study the TFR of luminous spirals and its relation to AM using the EAGLE set of ... cold dark matter (...CDM) cosmological simulations. Matching both relations requires disc sizes to satisfy constraints given by the concentration of haloes and their response to galaxy assembly. EAGLE galaxies approximately match these constraints and show a tight mass-velocity scaling that compares favourably with the observed TFR. The TFR is degenerate to changes in galaxy formation efficiency and the mass-size relation; simulations that fail to match the galaxy stellar mass function may fit the observed TFR if galaxies follow a different mass-size relation. The small scatter in the simulated TFR results because, at fixed halo mass, galaxy mass and rotation speed correlate strongly, scattering galaxies along the main relation. EAGLE galaxies evolve with lookback time following approximately the prescriptions of AM models and the observed mass-size relation of bright spirals, leading to a weak TFR evolution consistent with observation out to z = 1. ...CDM models that match both the abundance and size of galaxies as a function of stellar mass have no difficulty reproducing the observed TFR and its evolution. (ProQuest: ... denotes formulae/symbols omitted.)
The COVID-19 pandemic has had a profound impact on the nation’s health care system, including on graduate medical education (GME) training programs. Traditionally, residency and fellowship training ...program applications involve in-person interviews conducted on-site, with only a minority of programs offering interviews remotely via a virtual platform. However, in light of the COVID-19 pandemic, it is anticipated that most interviews will be conducted virtually for the 2021 application cycle, and possibly beyond. Therefore, GME training programs need to prepare for the transition to virtual interviews using evidence-based practices. At the University of California, San Francisco, a multidisciplinary task force was convened to review existing literature about virtual interviews and determine best practices. This article summarizes these findings, first discussing the advantages and disadvantages of the virtual interview format and then providing evidence-based best practices for GME training programs. Specifically, the authors make the following recommendationsdevelop a detailed plan for the interview process, consider using standardized interview questions, recognize and respond to potential biases that may be amplified with the virtual interview format, prepare your own trainees for virtual interviews, develop electronic materials and virtual social events to approximate the interview day, and collect data about virtual interviews at your own institution. With adequate preparation, the virtual interview experience can be high-yield, positive, and equitable for both applicants and GME training programs.
Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty ...years of age
. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine
in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Health services across the world increasingly face pressures on the use of expensive hospital services. Better organisation and delivery of primary care has the potential to manage demand and reduce ...costs for hospital services, but routine primary care services are not open during evenings and weekends. Extended access (evening and weekend opening) is hypothesized to reduce pressure on hospital services from emergency department visits. However, the existing evidence-base is weak, largely focused on emergency out-of-hours services, and analysed using a before-and after-methodology without effective comparators.
Throughout 2014, 56 primary care practices (346,024 patients) in Greater Manchester, England, offered 7-day extended access, compared with 469 primary care practices (2,596,330 patients) providing routine access. Extended access included evening and weekend opening and served both urgent and routine appointments. To assess the effects of extended primary care access on hospital services, we apply a difference-in-differences analysis using hospital administrative data from 2011 to 2014. Propensity score matching techniques were used to match practices without extended access to practices with extended access. Differences in the change in "minor" patient-initiated emergency department visits per 1,000 population were compared between practices with and without extended access. Populations registered to primary care practices with extended access demonstrated a 26.4% relative reduction (compared to practices without extended access) in patient-initiated emergency department visits for "minor" problems (95% CI -38.6% to -14.2%, absolute difference: -10,933 per year, 95% CI -15,995 to -5,866), and a 26.6% (95% CI -39.2% to -14.1%) relative reduction in costs of patient-initiated visits to emergency departments for minor problems (absolute difference: -£767,976, -£1,130,767 to -£405,184). There was an insignificant relative reduction of 3.1% in total emergency department visits (95% CI -6.4% to 0.2%). Our results were robust to several sensitivity checks. A lack of detailed cost reporting of the running costs of extended access and an inability to capture health outcomes and other health service impacts constrain the study from assessing the full cost-effectiveness of extended access to primary care.
The study found that extending access was associated with a reduction in emergency department visits in the first 12 months. The results of the research have already informed the decision by National Health Service England to extend primary care access across Greater Manchester from 2016. However, further evidence is needed to understand whether extending primary care access is cost-effective and sustainable.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The presence of substructure in galaxy groups and clusters is believed to be a sign of recent galaxy accretion and can be used to probe not only the assembly history of these structures, but also the ...evolution of their member galaxies. Using the Dressler-Shectman (DS) test, we study substructure in a sample of intermediate-redshift (z∼ 0.4) galaxy groups from the Group Environment and Evolution Collaboration (GEEC) group catalogue. We find that four of the 15 rich GEEC groups, with an average velocity dispersion of ∼525 km s−1, are identified as having significant substructure. The identified regions of localized substructure lie on the group outskirts and in some cases appear to be infalling. In a comparison of galaxy properties for the members of groups with and without substructure, we find that the groups with substructure have a significantly higher fraction of blue and star-forming galaxies and a parent colour distribution that resembles that of the field population rather than the overall group population. In addition, we observe correlations between the detection of substructure and other dynamical measures, such as velocity distributions and velocity dispersion profiles. Based on this analysis, we conclude that some galaxy groups contain significant substructure and that these groups have properties and galaxy populations that differ from groups with no detected substructure. These results indicate that the substructure galaxies, which lie preferentially on the group outskirts and could be infalling, do not exhibit signs of environmental effects, since little or no star formation quenching is observed in these systems.
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