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Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care. We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0–1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436. Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8–4·6) for radiographic progression-free survival and 4·4 years (3·5–5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41–0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69–0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34–0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59–0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone. Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients. Janssen-Cilag, Ipsen, Sanofi, and the French Government.

Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer. We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3–T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m2 and estramustine 10 mg/kg per day on days 1–5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731. We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1–9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55–69) in the ADT plus docetaxel and estramustine group versus 50% (44–57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54–0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths. Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival. Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.

Rhodiola rosea extract is purported to improve physical performance and support resilience to stress. Salidroside is considered to be one of the main constituents responsible for the ergogenic actions of R. rosea. However, R. rosea extract contains relatively little salidroside and cultivation of R. rosea is challenging as it is mainly found in high-altitude, cold regions. Additionally, the R. rosea plant is subject to conservation concerns because of its growing popularity. The purpose of this exploratory study was to evaluate the short-term effects of pure, biosynthetic salidroside supplementation on exercise performance, mood state, and markers of inflammation and muscle damage in healthy active young adults. Fifty participants (30 M, 20F; 21 ± 4 yrs; 173 ± 8 cm; 74 ± 13 kg) were randomly assigned to either salidroside (60 mg/day for 16 days) or placebo supplementation and underwent peak oxygen uptake (VO peak), intermittent time-to-exhaustion (TTE), and local muscular endurance assessments, along with mood state evaluations using the Profile of Mood States (POMS). Blood samples were analyzed for erythropoietin, myoglobin, creatine kinase-MM, and C-reactive protein. Salidroside supplementation enhanced overall percent predicted oxygen uptake during high-intensity intermittent exercise (  < 0.01). An increase in serum myoglobin was observed 24 hours following exercise in the placebo group (  = 0.02) compared with baseline whereas no statistically significant increase was observed for the salidroside group indicating reduced exercise-induced muscle damage. Placebo group experienced a decrease in number of intervals performed during the TTE test (  = 0.03), and a decrease in friendliness (  < 0.01) and an increase in fatigue-inertia (  < 0.01) as reported by POMS. The salidroside group exhibited stable mood states and maintained performance levels during the time-to-exhaustion test. Salidroside supplementation may enhance oxygen utilization and mitigate exercise-induced muscle damage and fatigue, warranting further research on its long-term effects and potential as an adaptogen for active individuals.

We report high-quality ZnO thin films deposited at low temperature (200°C) by pulsed plasma-enhanced chemical vapor deposition (pulsed PECVD). Process byproducts are purged by weak oxidants N 2 O or CO 2 to minimize parasitic CVD deposition, resulting in high-refractive-index thin films. Pulsed-PECVD-deposited ZnO thin-film transistors were fabricated on plasma-enhanced atomic layer deposition (PEALD) Al 2 O 3 dielectric and have a field-effect mobility of 15 cm 2 /V s, subthreshold slope of 370 mV/dec, threshold voltage of 6.6 V, and current on/off ratio of 10 8 . Thin-film transistors (TFTs) on thermal SiO 2 dielectric have a field-effect mobility of 7.5 cm 2 /V s and threshold voltage of 14 V. For these devices, performance may be limited by the interface between the ZnO and the dielectric.

We report undoped ZnO films deposited at low temperature (200°C) using plasma-enhanced chemical vapor deposition (PECVD). ZnO thin-film transistors (TFTs) fabricated using ZnO and Al^sub 2^O^sub 3^ deposited in situ by PECVD with moderate gate leakage show a field-effect mobility of 10 cm^sup 2^/V s, threshold voltage of 7.5 V, subthreshold slope <1 V/dec, and current on/off ratios >10^sup 4^. Inverter circuits fabricated using these ZnO TFTs show peak gain magnitude (dV^sub out^/dV^sub in^) ~5. These devices appear to be strongly limited by interface states and reducing the gate leakage results in TFTs with lower mobility. For example, ZnO TFTs fabricated with low-leakage Al^sub 2^O^sub 3^ have mobility near 0.05 cm^sup 2^/V s, and five-stage ring-oscillator integrated circuits fabricated using these TFTs have a 1.2 kHz oscillation frequency at 60 V, likely limited by interface states. [PUBLICATION ABSTRACT]

Using a quality improvement framework to address racial and ethnic disparities in health care highlights multiple opportunities for federal and state governments to exert policy leverage, particularly through their roles as purchasers and regulators. Under such a framework, federal and state governments can expand their roles in collecting race/ethnicity data; define universal and meaningful race/ethnicity categories; more broadly disseminate standards for cultural competence; and demand the reduction of disparities through leveraging their status as collectively the largest U.S. health care payer. [PUBLICATION ABSTRACT]

Physicians today are experiencing frustration as changes in the health-care delivery systems in virtually all industrialised countries threaten the very nature and values of medical professionalism. Meetings among the European Federation of Internal Medicine, the American College of Physicians and American Society of Internal Medicine (ACP-ASIM), and the American Board of Internal Medicine (ABIM) have confirmed that physicians' views on professionalism are similar in quite diverse systems of health-care delivery. We share the view that medicine's commitment to the patient is being challenged by external forces of change within our societies.

Les activités de coordination et les pratiques coopératives interorganisationnelles engagées lors d’une démarche expérimentale de category management sont l’objet de cette recherche. La coordination de ces supply chains s’accomplit chemin faisant pour répondre au besoin d’intelligibilité de situations managériales ambiguës et incertaines et pour expérimenter des nouvelles actions conjointes. La coopération est résistible et volontariste : elle ne repose ni sur le clan ni sur le contrat mais sur une solidarité organique et une gestion créative et dialogique du pluralisme et des conflits. Inter-organizational coordinating activities and cooperative practices performed in the run of an experimental category management approach are the focus of this research. Coordination within and across these supply chains is a developmental process always in the making. It unfolds to make ambiguous and uncertain managerial situations more intelligible and to experiment novel possibilities of joint action. Cooperation is resistible and voluntarist: it is neither clan- nor contract-based but relies on an organic solidarity to manage in a creative and dialogical way the inevitable pluralism of views and conflicts.