Reporting of social deprivation in musculoskeletal trials: an analysis of 402 randomised controlled trials

Background: Social deprivation is broadly defined as the restriction of access an individual has to social or cultural interactions due to poverty, discrimination or other disadvantages. While social deprivation is a widely acknowledged determinant of outcome in musculoskeletal conditions, it remains unclear how this is considered in the conduct and interpretation of musculoskeletal trials.  Aim: To determine the frequently to which measures of social deprivation are reported in trials recruiting people with musculoskeletal diseases.  Materials and Methods: We conducted a Pubmed search of randomised controlled trials published between 01 January 2019 and 01 June 2020. We included full-text papers of trials recruiting people with musculoskeletal diseases, irrespective of intervention type or origin. We extracted data relating to trial characteristics, setting, trial design, funding source and musculoskeletal disease. We extracted data on any reported social deprivation index or measure of social deprivation based on internationally adopted indicators. We analysed data descriptively to summarise the reporting of each social deprivation index and measure of social deprivation within trials.  Results: From 2133 potentially eligible citations, 402 were eligible. Mean age of participants was 51.7 years; 63% were female. Trials most frequently recruited people with spinal pain (24.6%) or osteoarthritis (10.0%). Two trials (0.5%) reported social deprivation indices/scores. When assessed by discrete measures of social deprivation, 164 trials (40.8%) reported one or more social deprivation measures. The most commonly reported measures were morbidity (20.2%), employment status (17.7%) and educational attainment (15.5%). Race (6.7%), ethnicity (6.2%) and annual salary (1.3%) were infrequently reported. One trial (0.3%) presented subgroup results by social deprivation measures.  Discussion and Conclusion: Social deprivation is inconsistently reported in musculoskeletal trials. Trialists should report baseline measures of social deprivation in trial reports and aid generalisability to target population, and to examine whether social deprivation might modify treatment effects of interventions for musculoskeletal conditions

Within study comparisons and risk of bias in international development: Systematic review and critical appraisal

Background Many systematic reviews incorporate nonrandomised studies of effects, sometimes called quasi‐experiments or natural experiments. However, the extent to which nonrandomised studies produce unbiased effect estimates is unclear in expectation or in practice. The usual way that systematic reviews quantify bias is through “risk of bias assessment” and indirect comparison of findings across studies using meta‐analysis. A more direct, practical way to quantify the bias in nonrandomised studies is through “internal replication research”, which compares the findings from nonrandomised studies with estimates from a benchmark randomised controlled trial conducted in the same population. Despite the existence of many risks of bias tools, none are conceptualised to assess comprehensively nonrandomised approaches with selection on unobservables, such as regression discontinuity designs (RDDs). The few that are conceptualised with these studies in mind do not draw on the extensive literature on internal replications (within‐study comparisons) of randomised trials. Objectives Our research objectives were as follows: Objective 1: to undertake a systematic review of nonrandomised internal study replications of international development interventions. Objective 2: to develop a risk of bias tool for RDDs, an increasingly common method used in social and economic programme evaluation. Methods We used the following methods to achieve our objectives. Objective 1: we searched systematically for nonrandomised internal study replications of benchmark randomised experiments of social and economic interventions in low‐ and middle‐income countries (L&MICs). We assessed the risk of bias in benchmark randomised experiments and synthesised evidence on the relative bias effect sizes produced by benchmark and nonrandomised comparison arms. Objective 2: We used document review and expert consultation to develop further a risk of bias tool for quasi‐experimental studies of interventions (ROBINS‐I) for RDDs. Results Objective 1: we located 10 nonrandomised internal study replications of randomised trials in L&MICs, six of which are of RDDs and the remaining use a combination of statistical matching and regression techniques. We found that benchmark experiments used in internal replications in international development are in the main well‐conducted but have “some concerns” about threats to validity, usually arising due to the methods of outcomes data collection. Most internal replication studies report on a range of different specifications for both the benchmark estimate and the nonrandomised replication estimate. We extracted and standardised 604 bias coefficient effect sizes from these studies, and present average results narratively. Objective 2: RDDs are characterised by prospective assignment of participants based on a threshold variable. Our review of the literature indicated there are two main types of RDD. The most common type of RDD is designed retrospectively in which the researcher identifies post‐hoc the relationship between outcomes and a threshold variable which determines assignment to intervention at pretest. These designs usually draw on routine data collection such as administrative records or household surveys. The other, less common, type is a prospective design where the researcher is also involved in allocating participants to treatment groups from the outset. We developed a risk of bias tool for RDDs. Conclusions Internal study replications provide the grounds on which bias assessment tools can be evidenced. We conclude that existing risk of bias tools needs to be further developed for use by Campbell collaboration authors, and there is a wide range of risk of bias tools and internal study replications to draw on in better designing these tools. We have suggested the development of a promising approach for RDD. Further work is needed on common methodologies in programme evaluation, for example on statistical matching approaches. We also highlight that broader efforts to identify all existing internal replication studies should consider more specialised systematic search strategies within particular literatures; so as to overcome a lack of systematic indexing of this evidence

Josephson Coupling and Fiske Dynamics in Ferromagnetic Tunnel Junctions

We report on the fabrication of Nb/AlO_x/Pd_{0.82}Ni_{0.18}/Nb superconductor/insulator/ferromagnetic metal/superconductor (SIFS) Josephson junctions with high critical current densities, large normal resistance times area products, high quality factors, and very good spatial uniformity. For these junctions a transition from 0- to \pi-coupling is observed for a thickness d_F ~ 6 nm of the ferromagnetic Pd_{0.82}Ni_{0.18} interlayer. The magnetic field dependence of the \pi-coupled junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd_{0.82}Ni_{0.18} has an out-of-plane anisotropy and large saturation magnetization, indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes provides information on the junction quality factor and the relevant damping mechanisms up to about 400 GHz. Whereas losses due to quasiparticle tunneling dominate at low frequencies, the damping is dominated by the finite surface resistance of the junction electrodes at high frequencies. High quality factors of up to 30 around 200 GHz have been achieved. Our analysis shows that the fabricated junctions are promising for applications in superconducting quantum circuits or quantum tunneling experiments.Comment: 15 pages, 9 figure

Radiobiological outcomes, microdosimetric evaluations and monte carlo predictions in eye proton therapy

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves

Primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary Ewing's sarcoma or primitive neuroectodermal tumor of the genital tract of women is uncommon. Rarer still is its occurrence in the vagina, with only five cases described so far. Out of these, only one case was confirmed using molecular analysis.</p> <p>Case presentation</p> <p>We present an extremely rare case of Ewing's sarcoma or primitive neuroectodermal tumor in a 17-year-old Indian girl. She presented with a vaginal mass that was initially diagnosed as a malignant round cell tumor. Immunohistochemistry showed diffuse positivity for vimentin, membranous positivity for MIC2, and positivity for BCL2 and FLI-1. On the other hand, she was negative for cytokeratin, epithelial membrane antigen, desmin, Myo D-1, myogenin and smooth muscle actin. A diagnosis of primitive neuroectodermal tumor was thus offered. Furthermore, a molecular analysis of our patient using reverse transcription-polymerase chain reaction technique showed positivity for t(11; 22) (q24; q12) (EWSR1-FLI1), thus confirming the diagnosis of a Ewing's sarcoma/primitive neuroectodermal tumor. Our patient was offered chemotherapy on Institutional protocol EFT 2001.</p> <p>Conclusion</p> <p>This is a rare case of primary vaginal Ewing's sarcoma or primitive neuroectodermal tumor, which was confirmed with molecular analysis, in the youngest patient known so far. This study reinforces the value of integrating morphological features with membranous MIC2 positivity, along with application of molecular techniques in objective identification of an Ewing's sarcoma or primitive neuroectodermal tumor at uncommon sites.</p

Youth transitions as ‘wiki-transitions’ in youth policies platforms

The version of a journal article that has been accepted for publication in a journal. This is an Accepted Manuscript of an article published by Taylor & Francis in European Societies on 22/11/2019 available online: http://www.tandfonline.com/10.1080/14616696.2019.1690158.In recent years, a number of youth-focused online platforms have emerged which, in different ways, seek to support young people across Europe in building pathways to independent adulthood. In this article, we draw on data from Edgeryders, a recent youth policy research project, to reflect on the extent to which online discussion platforms are useful instruments for understanding the challenges youth face in their transitions to independent adulthood across Europe. Noting the collaborative emphasis articulated by both the project designers and participants, we ask how we might make sense of the data – and the meanings conveyed by that data – produced by online projects. We propose the notion of ‘wiki-transitions’ as a means of theorising young people’s use of online space to support their transitions to adulthood

Dwarf Copper-Gold Porphyry Deposits of the Buchim-Damjan-Borov Dol Ore District, Republic of Macedonia (FYROM)

The metallogenic aspects, tectonic setting, magmatism, structure, and composition of Au-and Ag-bearing porphyry copper deposits in the Buchim-Damjan-Borov Dol ore district and their genetic features are considered and compared with earlier published data. Special attention is paid to supergene gold in heavy concentrate halos of the Borov Dol deposit. The total Cu reserves of the deposits discussed in this paper do not exceed 150 kt. The Buchim deposit likely is the world's smallest deposit of this type currently involved in mining. A comprehensive study of these dwarf porphyry copper deposits is undertaken to answer questions on the conditions of their formation. How do they differ from formation conditions of giant deposits

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials.

BACKGROUND: Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). METHODS/DESIGN: A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. DISCUSSION: This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies