Real-World Use of Bevacizumab for Treatment of Advanced Ovarian Cancer Among Elderly Women in the U.S.

Bevacizumab, a targeted VEGF inhibitor, is recommended for treatment of advanced ovarian cancer based on clinical trials demonstrating improved progression-free survival when added to standard chemotherapy. This study describes demographic, clinical and social factors, and outcomes associated with bevacizumab use among ovarian cancer patients in the US Medicare 5% sample. Kaplan-Meier curves and propensity score-weighted Cox proportional hazards models were used to estimate overall survival (OS) comparing bevacizumab to non-bevacizumab regimens. Of 3,760 patients with a principal diagnosis of ovarian cancer from 2016 to 2019, 1,508 had at least one observed line of chemotherapy; 457 had a second line following a treatment-free interval (TFI) ≥60 days, of whom 52% (N=237) received bevacizumab. Receipt of bevacizumab did not vary by dual eligibility for Medicaid (an indicator of poverty) or residing in a vulnerable community (measured by the social vulnerability index). Patients receiving bevacizumab were more likely to have metastatic disease and a TFI ≤180 days (an indication of platinum-resistant disease) at second-line treatment initiation. Bevacizumab was associated with a modest survival advantage and lower relative risk of death (hazard ratio=0.80, 95% confidence interval=0.66, 0.97) among patients who received bevacizumab within 30 days after second-line initiation, particularly those younger than age 75

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Comparison of Skeletal Effects of Ovariectomy Versus Chemically Induced Ovarian Failure in Mice

Bone loss associated with menopause leads to an increase in skeletal fragility and fracture risk. Relevant animal models can be useful for evaluating the impact of ovarian failure on bone loss. A chemically induced model of menopause in which mice gradually undergo ovarian failure yet retain residual ovarian tissue has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). This study was designed to compare skeletal effects of VCD-induced ovarian failure to those associated with ovariectomy (OVX). Young (28 day) C57Bl/6Hsd female mice were dosed daily with vehicle or VCD (160 mg/kg/d, IP) for 15 days (n = 6–7/group) and monitored by vaginal cytology for ovarian failure. At the mean age of VCD-induced ovarian failure (∼6 wk after onset of dosing), a different group of mice was ovariectomized (OVX, n = 8). Spine BMD (SpBMD) was measured by DXA for 3 mo after ovarian failure and OVX. Mice were killed ∼5 mo after ovarian failure or OVX, and bone architecture was evaluated by μCT ex vivo. In OVX mice, SpBMD was lower than controls 1 mo after OVX, whereas in VCD-treated mice, SpBMD was not lower than controls until 2.9 mo after ovarian failure (p < 0.05). Both VCD-induced ovarian failure and OVX led to pronounced deterioration of trabecular bone architecture, with slightly greater effects in OVX mice. At the femoral diaphysis, cortical bone area and thickness did not differ between VCD mice and controls but were decreased in OVX compared with both groups (p < 0.05). Circulating androstenedione levels were preserved in VCD-treated mice but reduced in OVX mice relative to controls (p < 0.001). These findings support that (1) VCD-induced ovarian failure leads to trabecular bone deterioration, (2) bone loss is attenuated by residual ovarian tissue, particularly in diaphyseal cortical bone, and (3) the VCD mouse model can be a relevant model for natural menopause in the study of associated bone disorders

Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents.

BACKGROUND: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. METHODS: Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4-14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5-<25·0 kg/m(2). FINDINGS: All-cause mortality was minimal at 20·0-25·0 kg/m(2) (HR 1·00, 95% CI 0·98-1·02 for BMI 20·0-<22·5 kg/m(2); 1·00, 0·99-1·01 for BMI 22·5-<25·0 kg/m(2)), and increased significantly both just below this range (1·13, 1·09-1·17 for BMI 18·5-<20·0 kg/m(2); 1·51, 1·43-1·59 for BMI 15·0-<18·5) and throughout the overweight range (1·07, 1·07-1·08 for BMI 25·0-<27·5 kg/m(2); 1·20, 1·18-1·22 for BMI 27·5-<30·0 kg/m(2)). The HR for obesity grade 1 (BMI 30·0-<35·0 kg/m(2)) was 1·45, 95% CI 1·41-1·48; the HR for obesity grade 2 (35·0-<40·0 kg/m(2)) was 1·94, 1·87-2·01; and the HR for obesity grade 3 (40·0-<60·0 kg/m(2)) was 2·76, 2·60-2·92. For BMI over 25·0 kg/m(2), mortality increased approximately log-linearly with BMI; the HR per 5 kg/m(2) units higher BMI was 1·39 (1·34-1·43) in Europe, 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in east Asia, and 1·31 (1·27-1·35) in Australia and New Zealand. This HR per 5 kg/m(2) units higher BMI (for BMI over 25 kg/m(2)) was greater in younger than older people (1·52, 95% CI 1·47-1·56, for BMI measured at 35-49 years vs 1·21, 1·17-1·25, for BMI measured at 70-89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46-1·56, vs 1·30, 1·26-1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI. INTERPRETATION: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.UK MRC, BHF, NIHR; US NIHThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/S0140-6736(16)30175-

The return of the fifties: Trends in college students' values between 1952 and 1984

Five identical surveys were carried out in 1952, 1968–1969, 1974, 1979, and 1984 among undergraduate men at Dartmouth College and the University of Michigan to measure value trends. In most value domains the trends are U-shaped, showing that the trends from the fifties to the sixties and seventies have reversed, and attitudes in 1984 were either similar to the fifties or moving in that direction. The domains include traditional religion, career choice, faith in government and the military, advocacy of social constraints on deviant social groups, attitudes about free enterprise, government and economics, sexual morality, marijuana use, and personal moral obligations. Two attitude areas do not show a return of the fifties: (1) other-direction was high in 1952, then dropped to the sixties and did not rise; (2) the level of politicization rose greatly from 1952 to the sixties, then dropped again only slightly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45659/1/11206_2005_Article_BF01106623.pd

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Janet Hildebrand, October 6, 1979

Concert Program for Janet Hildebrand, October 6, 197

The effects of ability grouping on the achievement and self-esteem of year 7, rural students

Master of EducationThis study investigated the achievement and self-esteem effects of ability grouping of a cohort of Year 7 students in a small country secondary school. Intelligence was used as a control variable to determine whether ability grouping enhanced the academic performance of students. Results indicated that no inequitable spread of achievement benefit between high aptitude and mid-low aptitude groups occurred during the project. After eight months the differences between the groups on academic, general, home and social self-esteem subscales remained the same as at the beginning, although there was some non-significant evidence of a decrease in academic self-esteem in the mid-low aptitude groups. The academic self-esteem decrease was reflected in the general self-esteem of one of the mid-low aptitude groups but not in the other. The results were rather ambiguous with regard to academic self-esteem, with considerable variation occurring across the groups across different times