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

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 guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

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

Using PROGRESS-Plus to identify current approaches to the collection and reporting of equity-relevant data: a scoping review

Objectives: Our objectives were to identify what and how data relating to the social determinants of health are collected and reported in equity-relevant studies and map these data to the PROGRESS-Plus framework. Study Design and Setting: We performed a scoping review. We ran two systematic searches of MEDLINE and Embase for equityrelevant studies published during 2021. We included studies in any language without limitations to participant characteristics. Included studies were required to have collected and reported at least two participant variables relevant to evaluating individual-level social determinants of health. We applied the PROGRESS-Plus framework to identify and organize these data. Results: We extracted data from 200 equity-relevant studies, providing 962 items defined by PROGRESS-Plus. A median of 4 (interquartile range 5 2) PROGRESS-Plus items were reported in the included studies. 92% of studies reported age; 78% reported sex/gender; 65% reported educational attainment; 49% reported socioeconomic status; 45% reported race; 44% reported social capital; 33% reported occupation; 14% reported place and 9% reported religion. Conclusion: Our synthesis demonstrated that researchers currently collect a limited range of equity-relevant data, but usefully provides a range of examples spanning PROGRESS-Plus to inform the development of improved, standardized practices.Emma L. Karrana, Aidan G. Cashina, Trevor Barker, Mark A. Boyd, Alessandro Chiarotto, Omar Dewidar, Vina Mohabir, Jennifer Petkovic Saurab Sharma, Sinan Tejani, Peter Tugwell, G. Lorimer Mosele

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials.Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials.Results A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies.Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity

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