Importance Prostate cancer treatments are associated with side effects. Understanding the side effects of contemporary approaches to management of localized prostate could inform shared decision-making. Objective To compare the harms of radical prostatectomy (RP), radiation (EBRT) and active surveillance (AS). Design The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, cohort study of men diagnosed with localized prostate cancer in 2011–2012. This study reports follow up through August 2015. Setting Patients accrued from five Surveillance Epidemiology, and End Results registry sites and the Cancer of the Prostate Strategic Urologic Research Endeavor. Participants Men < 80 years old with clinical stage cT1-2 disease, prostate specific antigen < 50 ng/mL, enrolled within six months of diagnosis, who completed a baseline survey and at least 1 follow-up survey. Exposure Treatment with RP, EBRT or AS was ascertained within one year of diagnosis. Main Outcome and Measures Patient-reported function in sexual, urinary incontinence, urinary irritative, bowel, and hormonal domains on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Domain scores range from 0–100. Higher score indicates better function. Minimum clinically important difference defined as 10–12, 6, 5, 5, and 4, respectively. Results The cohort included 2550 men (mean age 63.8 years, 74% white, 55% intermediate or high risk), of whom 1523 (59.7%) underwent RP, 598 (23.5%) EBRT, and 429 (16.8%) AS. Men undergoing EBRT were older (mean age 68.1 vs. 61.5, p<0.001), and had worse baseline sexual function (mean EPIC domain score 52.3 vs. 65.2, p<0.001) than men undergoing RP. At 3 years, adjusted mean sexual domain score for men undergoing RP had declined more than for men undergoing EBRT (mean difference −11.9 points, 95% CI [−15.1, −8.7]). The difference in decline in sexual domain scores between EBRT and AS was not clinically significant (−4.3 points, 95% CI [−9.2, 0.7]). RP was associated with worse urinary incontinence than EBRT (−18.0 points, 95% CI [−20.5, −15.4]) or AS (−12.7 points, 95% CI [−16.0, −9.3]) and better urinary irritative symptoms compared to AS (5.2 points, 95% CI [3.2, 7.2]). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in global quality of life or disease-specific survival (3 deaths) were noted (99.7–100%). Conclusion and Relevance In this cohort of men with localized prostate cancer, RP was associated with a larger decline in sexual function and urinary incontinence than EBRT or AS after 3 years, and lesser urinary irritative symptoms compared to AS; however, there were no meaningful differences in bowel or hormonal function beyond 12 months and no meaningful differences in global quality of life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

Female orthopaedic surgeons had an increased risk of pregnancy complications, particularly preterm delivery, compared with the general U.S. population. We found an increased risk of increased risk of preterm labor and delivery in surgeons working more than sixty hours per week during pregnancy.

Context Enhanced recovery after surgery (ERAS) protocols aim to improve surgical outcomes by reducing variation in perioperative best practices. However, among published studies, results show a striking variation in the effect of ERAS pathways on perioperative outcomes after cystectomy. Objective To perform a systematic review of the literature and a meta-analysis comparing the effectiveness of ERAS versus standard care on perioperative outcomes after cystectomy. Evidence acquisition We performed a literature search of PubMed, EMBASE, Web of Science, Google Scholar, the Cochrane Library, and the health-related grey literature in February 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis and the Cochrane Handbook. Studies were reviewed according to criteria from the Oxford Centre for Evidence-Based Medicine. Thirteen studies (1493 total patients) met the inclusion criteria (ERAS: 801, standard care: 692). A pooled meta-analysis of all comparative studies was performed using inverse-weighted, fixed-effects models, and random-effects models. Publication bias was graphically assessed using contour-enhanced funnel plots and was formally tested using the Harbord modification of the Egger test. Evidence synthesis Pooled data showed a lower overall complication rate (risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.74–0.97, p = 0.017, I2 = 35.6%), a shorter length of stay (standardized mean difference: −0.87, 95% CI: −1.31 to −0.42, p = 0.001, I2 = 92.8%), and a faster return of bowel function (standardized mean difference: −1.02, 95% CI: −1.69 to −0.34, p = 0.003, I2 = 92.2%) in the ERAS group. No difference was noted for the overall readmission rates (RR: 0.74, 95% CI: 0.39–1.41, p = 0.36, I2 = 51.4%), although a stratified analysis showed a lower 30-d readmission rate in the ERAS group (RR: 0.39, 95% CI: 0.19–0.83, p = 0.015, I2 = 0%). Conclusions ERAS protocols reduce the length of stay, time-to-bowel function, and rate of complications after cystectomy. Patient summary Enhanced recovery after surgery pathways for cystectomy reduce complications and the amount of time patients spend in the hospital.

In Arabidopsis, a complex of Polycomb-group (PcG) proteins functions in the female gametophyte to control the initiation of seed development. Mutations in the PcG genes, including MEDEA (MEA) and FERTILIZATION-INDEPENDENT SEED 2 (FIS2), produce autonomous seeds where endosperm proliferation occurs in the absence of fertilization. By using a yeast two-hybrid screen, we identified MEA and a related protein, SWINGER (SWN), as SET-domain partners of FIS2. Localization data indicated that all three proteins are present in the female gametophyte. Although single-mutant swn plants did not show any defects, swn mutations enhanced the mea mutant phenotype in producing autonomous seeds. Thus, MEA and SWN perform partially redundant functions in controlling the initiation of endosperm development before fertilization in Arabidopsis.chromatin ͉ endosperm ͉ female gametophyte ͉ fertilization ͉ gene silencing I n angiosperms, seed development is initiated by a doublefertilization event within the female gametophyte (FG). The pollen tube delivers two sperm cells that fuse with the haploid egg cell and the typically homodiploid central cell to initiate the development of two distinct organs, an embryo and an endosperm, respectively (1). The diploid embryo forms the next generation, whereas the typically triploid endosperm is a shortlived nutritive tissue that supports embryogenesis or seedling development. In most angiosperms, including Arabidopsis, the endosperm undergoes a nuclear-type development that includes an initial period of coenocytic development in which the primary endosperm nucleus undergoes mitosis without cytokinesis followed by cellularization. In Arabidopsis, the cellularized endosperm is gradually absorbed by the developing embryo, and only an aleurone layer remains at seed maturity (2, 3).Recent evidence indicates that the FG controls the initiation of seed development in Arabidopsis. Mutations in genes encoding the Polycomb-group (PcG) proteins FERTILIZATION-INDEPENDENT ENDOSPERM (FIE), MEDEA (MEA), FERTILIZATION-INDEPENDENT SEED 2 (FIS2), and the Arabidopsis homologue of MULTICOPY SUPPRESSOR OF IRA 1 (MSI1) cause the development of autonomous seeds in the absence of fertilization due mainly to proliferation of the diploid central cell nucleus. Molecular and genetic evidence indicates that these proteins are expressed in the FG and function to repress downstream genes required for normal endosperm proliferation before fertilization (4-11). The FIE, MEA, FIS2, and MSI1 genes encode proteins that are highly similar to components of the Polycomb repressive complex 2͞3 (PRC2͞3) that include the Drosophila Esc, E(z), Su(z)12, and p55 and the mammalian EED, EZH2, SUZ12, and RbAp48͞46, respectively (12). PRC2͞3 and the larger PRC1 complex function to silence and maintain epigenetic silencing of target genes involved in regulation of early development, cell growth, and proliferation. At least part of the gene-silencing function of PRC2͞3 is likely mediated through its intrinsic histone H3 methylation activity (13, 1...