The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Pilot assessment of the sensitivity of the malaria thin film

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Measuring subluxation of the hemiplegic shoulder: Reliability of a method

Objective: Subluxation of the shoulder after stroke can be measured according to the method described by Van Langenberghe and Hogan. Methods: To evaluate the reliability of this method, the shoulder radiographs of 25 patients were available for this study. Two independent raters each assessed these radiographs twice. Results: The intrarater reliability was good: percentage of agreement was 88 and 84%, weighted κ, 0.69 [95% confidence interval (CI), 0.38-1 0] and 0.78 (95% CI, 0.60-0.95) for raters 1 and 2, respectively. The interrater reliability was poor: percentage of agree ment was 36 and 28%, κ, 0.11 (95% CI, 0.0-0.31) and 0.09 (95% CI, 0.0-0.23) in sessions 1 and 2, respectively. Subsequently the original method was adjusted by com bining two categories (no subluxation and beginning subluxation) into one (“no clin ically important subluxation”). Conclusions: After this adjustment of the categories, the interrater reliability improved [percentage of agreement, 72%, and κ, 0.49 (95% CI, 0.18-0.80)], but did not reach acceptable values

MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer

Cell–cell adhesions constitute the structural “glue” that retains cells together and contributes to tissue organisation and physiological function. The integrity of these structures is regulated by extracellular and intracellular signals and pathways that act on the functional units of cell adhesion such as the cell adhesion molecules/adhesion receptors, the extracellular matrix (ECM) proteins and the cytoplasmic plaque/peripheral membrane proteins. In advanced cancer, these regulatory pathways are dysregulated and lead to cell–cell adhesion disassembly, increased invasion and metastasis. The Metastasis suppressor protein 1 (MTSS1) plays a key role in the maintenance of cell–cell adhesions and its loss correlates with tumour progression in a variety of cancers. However, the mechanisms that regulate its function are not well-known. Using a system biology approach, we unravelled potential interacting partners of MTSS1. We found that the secretory carrier-associated membrane protein 1 (SCAMP1), a molecule involved in post-Golgi recycling pathways and in endosome cell membrane recycling, enhances Mtss1 anti-invasive function in HER2+/ER−/PR− breast cancer, by promoting its protein trafficking leading to elevated levels of RAC1-GTP and increased cell–cell adhesions. This was clinically tested in HER2 breast cancer tissue and shown that loss of MTSS1 and SCAMP1 correlates with reduced disease-specific survival. In summary, we provide evidence of the cooperative roles of MTSS1 and SCAMP1 in preventing HER2+/ER−/PR− breast cancer invasion and we show that the loss of Mtss1 and Scamp1 results in a more aggressive cancer cell phenotype

A spatiotemporal Data Envelopment Analysis (S-T DEA) approach:the need to assess evolving units

One of the major challenges in measuring efficiency in terms of resources and outcomes is the assessment of the evolution of units over time. Although Data Envelopment Analysis (DEA) has been applied for time series datasets, DEA models, by construction, form the reference set for inefficient units (lambda values) based on their distance from the efficient frontier, that is, in a spatial manner. However, when dealing with temporal datasets, the proximity in time between units should also be taken into account, since it reflects the structural resemblance among time periods of a unit that evolves. In this paper, we propose a two-stage spatiotemporal DEA approach, which captures both the spatial and temporal dimension through a multi-objective programming model. In the first stage, DEA is solved iteratively extracting for each unit only previous DMUs as peers in its reference set. In the second stage, the lambda values derived from the first stage are fed to a Multiobjective Mixed Integer Linear Programming model, which filters peers in the reference set based on weights assigned to the spatial and temporal dimension. The approach is demonstrated on a real-world example drawn from software development

Association of internet addiction With nonsuicidal self-injury among adolescents in China

© 2020 The Authors. Published by American Medical Association. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: 10.1001/jamanetworkopen.2020.6863Importance: Both nonsuicidal self-injury (NSSI), defined as the direct, deliberate damage of one's body tissue without suicidal intent, and internet addiction among adolescents are public health concerns. However, the possible association of NSSI with internet addiction is not well understood. Objective: To examine the occurrence of internet addiction with NSSI and any sex differences among Chinese adolescents. Design, Setting, and Participants: A multicenter, cross-sectional, survey study was conducted from February 18 to October 15, 2015, among adolescents aged 11 to 20 years from 343 classes in 45 public high schools across 5 provinces of China. Data analysis was performed from August 1, 2018, to March 1, 2019. Exposures: Possible internet addiction and internet addiction. Main Outcomes and Measures: Less-frequent (1-4 times) NSSI and more-frequent (≥5 times) NSSI were surveyed using the Chinese version of the Functional Assessment of Self-Mutilation. Results: A total of 15 623 students (8043 male [51.5%] and 7580 female [48.5%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) participated. Of these, 4670 participants (29.9%) met the criteria for possible internet addiction and 509 participants (3.3%) met the criteria for internet addiction. A total of 2667 students (17.1%) engaged in less-frequent NSSI, while 1798 students (11.5%) engaged in more-frequent NSSI in the 12 months preceding the survey. Both possible internet addiction and internet addiction were associated with less-frequent or more-frequent NSSI. The adjusted odds ratios were 1.29 (95% CI, 1.17-1.42) for possible internet addiction and 1.41 (95% CI, 1.11-1.80) for internet addiction for less-frequent NSSI; for more-frequent NSSI, the adjusted odds ratios were 1.75 (95% CI, 1.56-1.96) for possible internet addiction and 2.66 (95% CI, 2.10-3.38) for internet addiction. These associations were similarly observed among age groups of 11 to 14, 15 to 17, and 18 to 20 years. No sex disparities were found in the associations of internet addiction with NSSI, except among adolescents aged 11 to 14 years, where the odds ratios for possible internet addiction with less-frequent NSSI were higher in male adolescents (1.53; 95% CI, 1.25-1.88) than female adolescents (1.13; 95% CI, 0.90-1.47). Conclusion and Relevance: Internet addiction appears to be associated with NSSI, and the findings of this study suggest that the association was similar between male adolescents and female adolescents. These data suggest that evaluation of the risk of NSSI for adolescents in association with internet addiction may help health care professionals in developing preventive interventions for NSSI.This study was supported by grants from National Natural Science Foundation of China (81773457, 81302445 [Dr Tang], and 81373022 [Dr Yu]), and a European Union grant from Horizon 2020 MSCA (DEMAIRPO 799247 [Drs Tang and Chen]).Published versio

Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women ≥ 70 years: Study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial

<p>Abstract</p> <p>Background</p> <p>Postmenopausal women are prone to develop functional disabilities as a result of reduction in muscle strength and muscle mass caused by diminished levels of female sex hormones. While hormone replacement therapy may counteract these changes, conventional hormone replacement therapy is associated with potential harmful effects, such as an increased risk of breast cancer, and its prescription is not recommended. For this reason newer alternative drugs, such as tibolone, a synthetic steroid with estrogenic, progestogenic and androgenic activity, and raloxifene, a selective estrogen receptor modulator, may be more appropriate. This trial investigates the effect of tibolone and raloxifene on muscle strength.</p> <p>Methods</p> <p>We recruited 318 elderly women in our single-center randomized, double-blind, double-dummy, placebo-controlled trial. Participants were randomized to tibolone 1.25 mg (Org OD 14, Organon NV, the Netherlands) plus placebo, raloxifene 60 mg (Evista^®, Eli Lilly, United States) plus placebo or two placebo tablets daily for 24 months.</p> <p>The primary aim is to determine if there is a difference between tibolone and placebo or if there is a difference between raloxifene and placebo. Primary endpoints are muscle strength and bone mineral density. The secondary endpoints are postural balance, body composition, cognitive function, anxiety, mood and quality of life. The secondary aim is to determine if there is a difference between tibolone and raloxifene.</p> <p>The measure of effect is the change from the baseline visit to the visits after 3 months, 6 months, 12 months, and 24 months. A follow-up measurement is planned at 30 months to determine whether any effects are sustained after cessation of the study. By December 2007 the blind will be broken and the data analyzed.</p> <p>Trial registration number</p> <p>NTR: 1232</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Hygienic characteristics of radishes grown in soil contaminated with Stenotrophomonas maltophilia

Background: Stenotrophomonas maltophilia is a plant growth-promoter. This bacterium is also implicated in human diseases. Thus, after the use of this bacterium in agriculture, the safety of the final products has to be verified. Due to the ubiquitous presence of S. maltophilia in soil, in this study a massive contamination was simulated to evaluate the growth and safety of Raphanus sativus L.. Results: Different inoculums and soil treatment conditions were tested. Soils were analysed weekly and the radishes at harvest for their microbial loads and presence/persistence of S. maltophilia LMG 6606. The concentration of the bacterium added in the different trials decreased during the first week, but increased thereafter and determined a significant increase of growth parameters of radishes. Conclusions: The addition of S. maltophilia LMG 6606 to non-autoclaved soil enhanced the productivity of radishes. The bacterium did not internalize in the hypocotyls, but colonized the external surface ensuring the safety of the products. Thus, a sanitizing bath of hypocotyls before consumption is necessary

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO