The effect of RU486 administered during the proliferative and secretory phase of the cycle on the bleeding pattern, hormonal parameters and the endometrium

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P2-G), oestrone glucuronide (E1-G), oestradiol (E2), progesterone (P4), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment. In four of these women the bleeding was scanty and followed by a menstrual-like bleeding at expected time, while in the remaining five volunteers the treatment bleeding was heavier and not followed by a new bleeding until a month later. The duration of the secretory phase was 16.5 ± 1.3 days in women with two bleeding episodes and 11.8 ± 1.9 days in women with one bleeding episode (P < 0.05). The hormonal parameters were similar in both groups up to the start of the treatment. In the patients with one bleeding episode, the treatment was associated with a reduction in progesterone concentration, while in the patients with two bleeding episodes the progesterone concentration remained elevated until the second bleeding episode. Light microscopic examination of the endometrium revealed unique changes in the endometrial morphology. The results indicate that RU486 acts mainly on the endometrium but a direct or indirect effect on the corpus luteum cannot be excluded. The age of the corpus luteum may be of importance for its susceptibility to RU486 treatmen

Quality indicators in radiation oncology: proposal of the Spanish Society of Radiation Oncology (SEOR) for a continuous improvement of the quality of care in oncology.

Purpose Current cancer treatment options include surgical intervention, radiotherapy, and chemotherapy. The quality of the provision of each of them and their effective coordination determines the results in terms of benefit/risk. Regarding the radiation oncology treatments, there are not stabilised quality indicators to be used to perform control and continuous improvement processes for healthcare services. Therefore, the Spanish Society of Radiation Oncology has undertaken a comprehensive project to establish quality indicators for use with the information systems available in most Spanish healthcare services. Methods A two-round Delphi study examines consensus of several possible quality indicators (n = 28) in daily practice. These indicators were defined after a bibliographic search and the assessment by radiation oncology specialists (n = 8). They included aspects regarding treatment equipment, patient preparation, treatment, and follow-up processes and were divided in structure, process, and outcome indicators. Results After the evaluation of the defined quality indicators (n = 28) by an expert panel (38 radiation oncologist), 26 indicators achieved consensus in terms of agreement with the statement. Two quality indicators did not achieve consensus. Conclusions There is a high degree of consensus in Spanish Radiation Oncology specialists on which indicators in routine clinical practice can best measure quality. These indicators can be used to classify services based on several parameters (patients, equipments, complexity of the techniques used, and scientific research). Furthermore, these indicators allow assess our current situation and set improvements’ objectives.pre-print241 K

A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention

Improved constraints on the expansion rate of the Universe up to z~1.1 from the spectroscopic evolution of cosmic chronometers

We present new improved constraints on the Hubble parameter H(z) in the redshift range 0.15 < z < 1.1, obtained from the differential spectroscopic evolution of early-type galaxies as a function of redshift. We extract a large sample of early-type galaxies (\sim11000) from several spectroscopic surveys, spanning almost 8 billion years of cosmic lookback time (0.15 < z < 1.42). We select the most massive, red elliptical galaxies, passively evolving and without signature of ongoing star formation. Those galaxies can be used as standard cosmic chronometers, as firstly proposed by Jimenez & Loeb (2002), whose differential age evolution as a function of cosmic time directly probes H(z). We analyze the 4000 {\AA} break (D4000) as a function of redshift, use stellar population synthesis models to theoretically calibrate the dependence of the differential age evolution on the differential D4000, and estimate the Hubble parameter taking into account both statistical and systematical errors. We provide 8 new measurements of H(z) (see Tab. 4), and determine its change in H(z) to a precision of 5-12% mapping homogeneously the redshift range up to z \sim 1.1; for the first time, we place a constraint on H(z) at z \neq 0 with a precision comparable with the one achieved for the Hubble constant (about 5-6% at z \sim 0.2), and covered a redshift range (0.5 < z < 0.8) which is crucial to distinguish many different quintessence cosmologies. These measurements have been tested to best match a \Lambda CDM model, clearly providing a statistically robust indication that the Universe is undergoing an accelerated expansion. This method shows the potentiality to open a new avenue in constrain a variety of alternative cosmologies, especially when future surveys (e.g. Euclid) will open the possibility to extend it up to z \sim 2.Comment: 34 pages, 15 figures, 6 tables, published in JCAP. It is a companion to Moresco et al. (2012b, http://arxiv.org/abs/1201.6658) and Jimenez et al. (2012, http://arxiv.org/abs/1201.3608). The H(z) data can be downloaded at http://www.physics-astronomy.unibo.it/en/research/areas/astrophysics/cosmology-with-cosmic-chronometer

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Educational readiness among health professionals in rheumatology: low awareness of EULAR offerings and unfamiliarity with the course content as major barriers: results of a EULAR-funded European survey

Background: Ongoing education of health professionals in rheumatology (HPR) is critical for high-quality care. An essential factor is education readiness and a high quality of educational offerings. We explored which factors contributed to education readiness and investigated currently offered postgraduate education, including the European Alliance of Associations for Rheumatology (EULAR) offerings. Methods and participants: We developed an online questionnaire, translated it into 24 languages and distributed it in 30 European countries. We used natural language processing and the Latent Dirichlet Allocation to analyse the qualitative experiences of the participants as well as descriptive statistics and multiple logistic regression to determine factors influencing postgraduate educational readiness. Reporting followed the Checklist for Reporting Results of Internet E-Surveys guideline. Results: The questionnaire was accessed 3589 times, and 667 complete responses from 34 European countries were recorded. The highest educational needs were 'professional development', 'prevention and lifestyle intervention'. Older age, more working experience in rheumatology and higher education levels were positively associated with higher postgraduate educational readiness. While more than half of the HPR were familiar with EULAR as an association and the respondents reported an increased interest in the content of the educational offerings, the courses and the annual congress were poorly attended due to a lack of awareness, comparatively high costs and language barriers. Conclusions: To promote the uptake of EULAR educational offerings, attention is needed to increase awareness among national organisations, offer accessible participation costs, and address language barriers.Orthopaedics, Trauma Surgery and Rehabilitatio