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Russia, in its competition with the liberal world for establishing the dominant discourse—alongside hard power military means—deploys soft power, leveraging the allure of illiberal values to forge foreign policy alliances, undermine the credibility of international institutions, and reshape the global order. Russian strategic narratives delineate the political objectives of the Russian government. In a contest for discursive authority with other global actors, Russia presents its vision of a new world order—a world partitioned among major powers—where Moscow holds the authority to determine the fate of peoples in the "Greater Eurasia" region, including Europe [ABSTRACT FROM AUTHOR]

The US-led, rules-based order enables China to pursue a peaceful international power transition by leveraging the agenda-setting power. The agenda that China proposes is development, and the lever to promote the agenda is the Belt and Road Initiative (BRI). The BRI helps China publicize the development agenda, co-opt the existing US-led system, showcase China's material success, legitimize its creation of new international institutions, and attract supporters of its calls to revise the current US-led order. Since Washington wants to avoid its competition with China turning apocalyptic, the most sensible US countermeasure is keeping China inside this rules-based order and competing to set its agenda. [ABSTRACT FROM AUTHOR]

Since its emergence in the early 1990s, hemovigilance has gradually evolved from a blood safety concept focused on surveillance of adverse reactions and events in patients, to a well-defined system that monitors the entire transfusion chain and improves its safety. The importance of hemovigilance has been recognized globally in a relatively short time, but the level of its implementation varies significantly between countries. The cooperation of international organizations has significantly contributed to the promotion, implementation, and education in this field. Thanks to initiatives taken, the safety of transfusion practice has been improved in many segments, primarily related to the risks of adverse events in recipients of blood components. In parallel with changing transfusion practice, the hemovigilance process has also matured. In addition to the reduction of existing risks and the early detection of emerging risks, hemovigilance has also embraced the principles of patient blood management. Research in hemovigilance is more increasingly focused on specific categories of patients, specific blood components and methods of their preparation, rare reactions, and transfusion efficacy and efficiency. A proactive approach and use of big data can play an important role in achieving these goals. Additional and sustained efforts should be made to prevent underreporting of events and to improve data comparability through clear definitions and grading systems. This review provides a historical overview of hemovigilance and its achievements, current challenges, and future plans. [ABSTRACT FROM AUTHOR]

Paclitaxel, one of the most frequently used anticancer drugs, is dosed by body surface area, which leads to substantial inter-individual variability in systemic drug exposure. We evaluated clinical evidence regarding the scientific rationale and clinical benefit of individualized paclitaxel dosing based on measured systemic concentrations, known as therapeutic drug monitoring (TDM). In retrospective studies, higher systemic exposure is associated with greater toxicity and efficacy of paclitaxel treatment across several disease types and dosing regimens. In prospective trials, TDM reduces variability in systemic exposure, and has been demonstrated to reduce toxicity while retaining treatment efficacy for 3-weekly dosing in patients with advanced non-small cell lung cancer. Despite the demonstrated benefits of paclitaxel TDM, clinical adoption has been limited due to the challenges with sample collection and analysis. Based on our review, we strongly recommend TDM for patients receiving every 3-week paclitaxel in combination with a platinum agent for advanced NSCLC, due to the prospectively demonstrated clinical benefits, and find moderate evidence to recommend TDM for paclitaxel 3-hour infusions for other tumor types and preliminary evidence suggesting potential usefulness for paclitaxel administered by 1-hour infusions. • BSA-based dosing does not meaningfully reduce inter-patient variability in exposure. • Significant correlations exist between paclitaxel exposure and toxicity. • Significant correlations exist between paclitaxel exposure and activity. • In randomized trials, TDM lowers paclitaxel exposure variability and improves safety. • We strongly recommend TDM for NSCLC patients receiving Q3W paclitaxel. [ABSTRACT FROM AUTHOR]

The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system. The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (−27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel's concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020). With FIGO's 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management. • FIGO's 2023 endometrial cancer staging system adds many variables and stage groups. • Stage migration using this new system is greatest in stage I and II disease. • Discrimination of survival appears to be more precise using 2023 classifications. • Molecular testing should play an increasingly important role in clinical decisions. • Staging changes will likely affect practice paradigms in the coming years. [ABSTRACT FROM AUTHOR]

Rapid evaluation and subsequent regulatory approval of new drugs are critical to improving survival and reducing long-term side-effects for children and adolescents with cancer. The international multi-stakeholder organisation ACCELERATE was created to advance the timely investigation of new anti-cancer drugs. ACCELERATE has enhanced communication and understanding between academia, industry, patient advocates and regulators. It has promoted a mechanism-of-action driven drug development approach and developed Paediatric Strategy Forums. These initiatives have facilitated prioritisation of medicinal products and a focused and sequential strategy for drug development where there are multiple potential agents. ACCELERATE has championed the early assessment of promising drugs in adolescents through their inclusion in adult early phase trials. ACCELERATE has strongly supported alignment between the European Medicines Agency and the US Food and Drug Administration and identification of unmet medical needs through multi-stakeholder collaboration. Early engagement between all stakeholders in the development of new drugs is critical. Innovative clinical trial designs are required, necessitating early discussion with sponsors and regulators. Amplifying the patient advocate voice through inclusion across the drug development continuum will lead to better, patient-centric trials. By these means, children and adolescents with cancer can maximally and rapidly benefit from innovative products to improve outcomes and reduce burdensome sequelae. • The multi-stakeholder group ACCELERATE aims to advance investigation of new drugs. • ACCELERATE promotes a mechanism-of-action approach and Paediatric Strategy Forums. • Early engagement of all stakeholders in the development of new drugs is critical. • Identification of unmet medical needs by multi-stakeholder collaboration is vital. • The patient advocate voice needs to be amplified in all areas of drug development. [ABSTRACT FROM AUTHOR]

Transport connectivity has increasing importance in the global economy. Using a gravity equation model, this paper investigates the effect of liner shipping connectivity on seaborne containerised exports. We use a dataset from the European Comext database that includes information about the transport mode and use of containers for trade flows between EU and non-EU countries. Measuring the dependent variable with the required accuracy and addressing the potential reverse causality between trade flows and shipping connectivity, we document a positive effect of liner shipping connectivity on seaborne containerised exports and a negative effect on seaborne non-containerised ones. The results of this paper support the policy recommendations of international institutions in terms of incentivizing liner shipping connectivity. • We addressed the reverse causality between liner shipping connectivity and trade. • The higher shipping connectivity is, the lower the share of non-containerised flows. • Improving shipping connectivity may be crucial for remote countries. • Reverse causality is an issue when analysing transportation channels. [ABSTRACT FROM AUTHOR]

Despite contributions provided by the recent clinical trials, several issues and challenges still remain unsolved in adjuvant colon cancer (CC). Hence, further studies should be planned to better refine risk assessment as well as to establish the optimal treatment strategy in the adjuvant setting. However, it is necessary to request adequate, contemporary and relevant variables and report them homogeneously in order to bring maximal information when analyzing their prognostic value. The project was devised to gain a consensus from experts engaged in the planning, accrual and analyses of stage II and III CC clinical trials, to identify mandatory and recommended baseline variables in order to i) harmonize future data collection worldwide in clinical trials dedicated to adjuvant treatment of CC; ii) propose guidance for Case Report Forms to be used for clinical trials in this setting. A total of 72 questions related to variables that should be reported and how to report them in adjuvant clinical trials were approved and then voted to reach a final consensus from panelists. Data items on patient-related factors, histopathological features, molecular profile, circulating biomarkers and blood analyses were analyzed and discussed by the whole expert panel. For each item, we report data supporting the acquired consensus and the relevant issues that were discussed. Nineteen items were deemed to be mandatory for resected stage III patients and 24 for resected stage II disease. In addition, 9 and 4 items were judged as recommended for stage III and II, respectively. In our opinion, these 28 variables should be used and uniformly reported in more comprehensive CRFs as research groups design future clinical trials in the field of adjuvant colon cancer. • Selection and reporting of variables in current adjuvant trials are heterogenous. • It is crucial to have uniformed and adequate variables to obtain maximal information. • We describe 28 variables which should be uniformly collected in CRFs for stage II-III CC. [ABSTRACT FROM AUTHOR]

Aggressive and violent behaviours often lead to the use of coercive interventions in health and forensic institutions. Restraint minimization is now a legal or governmental requirement in most jurisdictions. While physical restraint and seclusion are relatively well-understood, chemical restraint remains problematic to define and measure. The aim of this review is to explore the international understandings of chemical restraint and to formulate an operational definition to support the development of quality indicators and care standards. This review was the first step prior to a realist synthesis to clarify the scope of chemical restraint intervention. PRISMA extension for Scoping Review was used. A keyword-based literature review (2006–2020, French and English) was conducted in health and social science databases. Chemical restraint or sedation of behavioural symptoms involves an emergency (STAT), as needed (PRN), regular or continuous medication with sedative properties, administered with the intention of preventing or controlling harmful behaviours or behaviours that interfere with diagnostic or therapeutic interventions, AND/OR administered to avoid physical restraint or seclusion; AND/OR without the person's consent. This first operational definition of chemical restraint could support the development of quality indicators in addition to allowing initiatives to improve health outcomes, safety and promote person-centred care. • Elimination of chemical restraint has been stated as a global priority. • No operational definition of chemical restraint or valid quality indicator exist. • Defining chemical restraint requires uncovering the intentions of the provider in charge of the administration. • This definition can support measurement, security and quality improvement. [ABSTRACT FROM AUTHOR]

The growing influence of cities is visible at the national level and in international politics. This new reality is leading to a paradigm shift in global politics and international law. As part of this new reality, cities demand recognition of their position. This paper aims to examine the already existing bodies that formally represent cities in the decision-making processes within some intergovernmental organizations' structures and answer the question about the need to create a new organ within the United Nations system that will better accommodate the growing role of cities in international relations. If the answer is positive, the attempt shall be made to consider what such an organ could look like. The novelty of this paper is that it is the first to provide some reflection on the possible status and composition of such a new UN body. • The growing role of cities in international relations has not been properly reflected in the structures of the UN. • The UN system should become more inclusive of cities rather than state-centric. • The UN General Assembly could create a new UN organ dedicated to cities. [ABSTRACT FROM AUTHOR]

• The scoping review identified robust examples of municipal youth councils internationally. • The origin, structure, activities, and impacts of municipal youth councils varied considerably. • The impacts were largely focused on the individual youth but there were select examples of community impacts. • There is a need for more systematic research documenting the best practices and impacts of municipal youth councils. Youth engagement in policy decision-making can benefit youth and their communities. Youth bodies at the municipal level, in the form of councils, commissions, and advisory boards, are one common mechanism to engage youth. There are numerous examples of municipal youth councils across the globe, yet no cross-county studies that compile the lessons from these efforts. The aim of the present study was to gather and synthesize research pertaining to municipal youth councils in an international context. The study used a scoping review protocol to collect and analyze data on the existence, origin, structure, activities, barriers, and impacts of municipal youth councils. The results show robust examples of municipal youth councils globally, however, there is wide variation in the origin, structure, and activities. Furthermore, there has been little attention to measure policy and community impacts. The study results demonstrate the promise of youth engagement in policy decision-making, but also the need for more systematic research documenting the best practices and impacts of municipal youth councils. [ABSTRACT FROM AUTHOR]

• The integration of returnees from the ISIS territory is carried out by state and religious authorities. • The access of international organizations and local NGOs is limited by the State. • Public discussion and community influence are controlled by the State • The strategy of total control in the name of security increases the stigmatization of returnees. • Families of returnees have limited access to medical care, psychological and legal support. This article analyzes the integration process of children returned from ISIS territory in three regions of the Russian North Caucasus from where the largest number of ISIS fighters with Russian citizenship originated. Following the concepts of "reintegration of returned migrants" and "cultural citizenship", it explicates the role of key actors in the processes of adaptation and integration of children and their families, as well as analyzes the nature of the barriers they overcome to restore their lost civil status and identity. The findings demonstrate that the process of reintegration of returnees is completely monopolized by the federal and local (republican) authorities and religious leaders. They limit the access of international organizations and local NGOs, minimize public discussion in the media, and control the influence of the local communities. Such a strategy of total control in the name of security as a target component of Russian domestic policy creates new grounds for vulnerability of returned children and their families, increasing their stigmatization and preserving hotbeds of tension, but does not allow this tension to be resolved through public dialogue and building constructive forms of civic integration. [ABSTRACT FROM AUTHOR]

Although therapeutic drug monitoring (TDM) is an important tool in guiding drug dosing for other areas of medicine including infectious diseases, cardiology, psychiatry and transplant medicine, it has not gained wide acceptance in oncology. For imatinib and other tyrosine kinase inhibitors, a flat dosing approach is utilised for management of oral chemotherapy. There are many published studies examining the correlation of blood concentrations with clinical effects of imatinib. The International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) determined that there was a need to examine the published literature regarding utility of TDM in imatinib therapy and to develop consensus guidelines for TDM based on the available data. This article summarises the scientific evidence regarding TDM of imatinib, as well as the consensus guidelines developed by the IATDMCT. • Imatinib is typically administered to patients in a flat rate dosing paradigm. • Many studies suggest monitoring imatinib blood concentrations optimises treatment. • The IATDMCT Oncology Committee has developed consensus guidelines for imatinib TDM. • The scientific evidence and consensus guidelines are summarised here. [ABSTRACT FROM AUTHOR]

The number of patients with cancer in Africa has been predicted to increase from 844 279 in 2012 to more than 1·5 million in 2030. However, many countries in Africa still lack access to radiotherapy as a part of comprehensive cancer care. The objective of this analysis is to present an updated overview of radiotherapy resources in Africa and to analyse the gaps and needs of the continent for 2030 in the context of the UN Sustainable Development Goals. Data from 54 African countries on teletherapy megavoltage units and brachytherapy afterloaders were extracted from the Directory for Radiotherapy Centres, an electronic, centralised, and continuously updated database of radiotherapy centres. Cancer incidence and future predictions were taken from the GLOBOCAN 2018 database of the International Agency for Research on Cancer. Radiotherapy need was estimated using a 64% radiotherapy utilisation rate, while assuming a machine throughput of 500 patients per year. As of March, 2020, 28 (52%) of 54 countries had access to external beam radiotherapy, 21 (39%) had brachytherapy capacity, and no country had a capacity that matched the estimated treatment need. Median income was an important predictor of the availability of megavoltage machines: US$1883 (IQR 914-3269) in countries without any machines versus $4485 (3079-12480) in countries with at least one megavoltage machine (p=0·0003). If radiotherapy expansion continues at the rate observed over the past 7 years, it is unlikely that the continent will meet its radiotherapy needs. This access gap might impact the ability to achieve the Sustainable Development Goals, particularly the target to reduce preventable, premature mortality by a third, and meet the target of the cervical cancer elimination strategy of 90% with access to treatment. Urgent, novel initiatives in financing and human capacity building are needed to change the trajectory and provide comprehensive cancer care to patients in Africa in the next decade. [ABSTRACT FROM AUTHOR]

Technological innovation is critical to secure long-term productivity benefits in any section of society. Investment in ICT is often seen as an imperative for improving banking efficiency. However, the unexpected failure of ICT in enhancing efficiency has unearthed the dilemma observed by Solow, who remarked, "You can see the computer age everywhere, except in productivity statistics". We analyze the impact of IT investments on the technical and cost efficiency of 72 Indian commercial banks across 2008–2019 using stochastic frontier analysis with exogeneous inefficiency effects and a slacks-based measure of data envelopment analysis. We conclude that the sector has been able to leverage IT investments towards improving efficiency, thereby invalidating the claims of a productivity paradox and providing evidence that supports the birth of a new economy where IT can be viewed as a dynamic force that brings about changes in organizational design, allowing banks to achieve better efficiency levels. [ABSTRACT FROM AUTHOR]

Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients. • A unique survey of current global paediatric radiotherapy practice. • Data from high-income countries showing what clinicians consider standard of care. • Many low- and middle-income countries lack multidisciplinary team working. • More patients in low-income settings are treated with palliative intent. • Leading centres in middle-income countries can train, mentor and drive up standards. [ABSTRACT FROM AUTHOR]

This study investigates a language ideological debate concerning the adoption of simplified Chinese script—the norm in China—at tourist spots in Taiwan, where traditional Chinese script is the norm, after Taiwan opened up its market to Chinese independent travelers in 2011. With discourse data from the government, media, hosts, and Chinese travelers, we explore how the scripts are associated with various meanings and how the debate is interwoven with the contestation of Taiwanese identity. Multiple levels of tension are identified, including those between the symbolic and instrumental values of the scripts and between Taiwan's national identity and marketing considerations. We conclude that discourses concerning the two Chinese scripts serve as a discursive space where 'Taiwaneseness' and 'Chineseness' are variously constructed and negotiated along two main axes of differentiation. • Chinese scripts are given diverse meanings in tourism discourse. • Tension is found between symbolic and instrumental values of the scripts. • Tension is found between Taiwan's national identity and marketing considerations. • Chineseness and Taiwaneseness operate on two axes of differentiation. • Chineseness and Taiwanese are seen as both compatible and oppositional. [ABSTRACT FROM AUTHOR]

Fine particulate air pollution <2.5 μm in diameter (PM2.5) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM2.5 as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM2.5 can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy. • The Neuroblastoma New Drug Development Strategy initiative aims to accelerate new drugs development. •Twenty two of 40 targets were identified as high priority for neuroblastoma. •Targeting telomere maintenance, ATRX , BRIP1 , RRM2 are high priority for drug discovery. •Drugs targeting CDK2/9, CDK7, ATR should enter paediatric clinical development rapidly. •Combining targeted therapies with immunological agents is crucial. [ABSTRACT FROM AUTHOR]

The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes. • Introduction of innovative medicines into paediatric acute myeloid leukaemia (AML) needs to be accelerated. • Trials of new agents in de novo AML should be embedded in cooperative group trials. • Prioritisation is required, as there are a limited number of deliverable studies. • The PedAL/EUpAL Master Trial should accelerate the evaluation of novel drugs. • Development of CD123-targeted drugs should be accelerated as a proof-of-concept. [ABSTRACT FROM AUTHOR]

Background: Estimates of government spending and development assistance for tuberculosis exist, but less is known about out-of-pocket and prepaid private spending. We aimed to provide comprehensive estimates of total spending on tuberculosis in low-income and middle-income countries for 2000-17.Methods: We extracted data on tuberculosis spending, unit costs, and health-care use from the WHO global tuberculosis database, Global Fund proposals and reports, National Health Accounts, the WHO-Choosing Interventions that are Cost-Effective project database, and the Institute for Health Metrics and Evaluation Development Assistance for Health Database. We extracted data from at least one of these sources for all 135 low-income and middle-income countries using the World Bank 2019 definitions. We estimated tuberculosis spending by source and function for notified (officially reported) and non-notified tuberculosis cases separately and combined, using spatiotemporal Gaussian process regression to fill in for missing data and estimate uncertainty. We aggregated estimates of government, out-of-pocket, prepaid private, and development assistance spending on tuberculosis to estimate total spending in 2019 US$.Findings: Total spending on tuberculosis in 135 low-income and middle-income countries increased annually by 3·9% (95% CI 3·0 to 4·6), from $5·7 billion (5·2 to 6·5) in 2000 to $10·9 billion (10·3 to 11·8) in 2017. Government spending increased annually by 5·1% (4·4 to 5·7) between 2000 and 2017, and reached $6·9 billion (6·5 to 7·5) or 63·5% (59·2 to 66·8) of all tuberculosis spending in 2017. Of government spending, $5·8 billion (5·6 to 6·1) was spent on notified cases. Out-of-pocket spending decreased annually by 0·8% (-2·9 to 1·3), from $2·4 billion (1·9 to 3·1) in 2000 to $2·1 billion (1·6 to 2·7) in 2017. Development assistance for country-specific spending on tuberculosis increased from $54·6 million in 2000 to $1·1 billion in 2017. Administrative costs and development assistance for global projects related to tuberculosis care increased from $85·3 million in 2000 to $576·2 million in 2017. 30 high tuberculosis burden countries of low and middle income accounted for 73·7% (71·8-75·8) of tuberculosis spending in 2017.Interpretation: Despite substantial increases since 2000, funding for tuberculosis is still far short of global financing targets and out-of-pocket spending remains high in resource-constrained countries, posing a barrier to patient's access to care and treatment adherence. Of the 30 countries with a high-burden of tuberculosis, just over half were primarily funded by government, while others, especially lower-middle-income and low-income countries, were still primarily dependent on development assistance for tuberculosis or out-of-pocket health spending.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

In 2017, EACH celebrated its change of name from European Association for Communication in Healthcare to EACH: International Association for Communication in Healthcare. This paper aims to present the developments and achievements of EACH over the past five years with a focus on its mission in promoting and advancing the field of communication in healthcare. Specifically, the paper focuses on how EACH, first, promotes research in the field of health communication, second, provides support, resources and sharing for healthcare communication teachers and, third, aims at influencing policy through dissemination of evidence. This paper also explores future challenges and directions for EACH to further strengthen its impact by designing activities in knowledge transfer and knowledge dissemination, engaging with patients and truly benefitting from their expertise, fostering active participation and networking among its members, targeting interventions to the needs of different countries around the world and refining knowledge-sharing and cooperation both within the membership of EACH and outside the association to as wide an audience as possible. Scholars, educators and practitioners active in the field of healthcare communication are invited to comment on this paper and to actively contribute towards the goals of EACH. [ABSTRACT FROM AUTHOR]

Abstract Prevention is an attractive idea to policymakers in theory, particularly in health where the burden of spending and care is increasingly taken up by complex and chronic conditions associated with lifestyle choices. However, prevention in general, and preventive health in particular, has proven hard to implement in practice. In this paper, we look to one tangible legacy of the recent rise of the prevention agenda: agencies with responsibility for preventive health policy. We ask how this form of institutionalizing preventive health happens in practice, and what consequences it has for the advancement of the prevention agenda. We draw on qualitative data to compare the trajectories of newly formed agencies in Australia, New Zealand and England. We find that building and maintaining legitimacy for such agencies may come at the expense of quick progress or radical action in service of the prevention agenda. Highlights • Executive agencies are no magic bullet for the prevention agenda in health. • The viability of agencies depends on a complex, evolving mix of factors. • Sustaining political support for an agency can undermine policy progress. • Agency officials often act as prevention 'ninjas' rather than bold public leaders. [ABSTRACT FROM AUTHOR]

Abstract Recent global commitments to shift responsibility for Neglected Tropical Disease (NTD) control to affected countries reflect a renewed emphasis on sustainability, away from aid-dependency. This calls for a better understanding of how domestic stakeholders perceive investments in different strategies for NTD control. Soil transmitted helminths (STH) are among the NTDs targeted for elimination as a public health problem by international agencies through mass drug administration, provided periodically to at-risk population groups, often using drugs donated by pharmaceutical companies. This study was conducted in Kenya at a time when responsibilities for long running STH programmes were transitioning from external to national and sub-national agencies. Following an initial assessment in which we identified key domestic stakeholders and reviewed relevant scientific and government documents, the perspectives of stakeholders working in health, education, community engagement and sanitation were investigated through semi-structured interviews with national level policymakers, county level policymakers, and frontline implementers in one high-STH burden county, Kwale. Our conceptual framework on sustainability traced a progression in thinking, from ensuring financial stability through the technical ability to adapt to changing circumstances, and ultimately to a situation where a programme is prioritised by domestic policymakers because empowered communities demand it. It was clear from our interviews that most Kenyan stakeholders sought to be at the final stage in this progression. Interviewees criticised long-term investment in mass drug administration, the approach favoured predominantly by external agencies, for failing to address underlying causes of STH. Instead they identified three synergistic priority areas for investment: changes in institutional structures and culture to reduce working in silos; building community demand and ownership; and increased policymaker engagement on underlying socioeconomic and environmental causes of STH. Although challenging to implement, the shift in responsibility from external agencies to domestic stakeholders may lead to emergence of new strategic directions. Highlights • Sustainability was not conceptualised as self-sufficiency to continue a programme. • Mass drug administration criticised for neglecting root causes of worm infestation. • Kenyan stakeholders linked sustainability to building community demand for health. • Community demand was seen as a precursor to increased political attention. • As Kenyan stakeholders lead on NTD control, investment strategies may change. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes (GDM) affects up to 7-18% of pregnant women and is associated with several maternal and perinatal morbidities. International organizations suggest several different recommendations regarding how to screen and to manage hyperglycemia in pregnancy (HIP).Objective: We aimed to analyze the most important and employed guidelines about screening and management of HIP and we investigated existing related literature.Results: We found several different criteria for screening for HIP, with the main difference being between non-USA-based IADPSG (One-step) approach, and the USA-based (Two-step) approach. The use of IADPSG approach (One-step) is associated with an increase in the incidence of GDM, improvement of several maternal and perinatal outcomes, and cost-effectiveness, compared to the USA-based Two-step criteria.Conclusions: As the One-Step approach endorsed by IADPSG, WHO, and FIGO is associated with maternal and perinatal benefits, it should be preferred to the Two-Step approach currently endorsed by the USA-based societies such as ACOG and SMFM. The hope is to approve universal screening guidelines based on the One-step approach to improve health care and reduce costs and adverse outcomes for women with GDM. [ABSTRACT FROM AUTHOR]

Climate targets set by international organizations require the implementation of innovative technologies that ensure the decarbonization of energy sector. It may be partially achieved through a large penetration of Renewable Energy Sources. Massive energy storage is essential to handle excess electricity associated to RES and Power-to-Gas represents a promising option to chemically convert electricity surplus into energy carriers that may attend demands substituting fossil fuels. Aiming to avoid the influence of policies and market implications, this study approaches the decarbonization of Spanish system through the analysis of technical potential of RES. Several scenarios with different shares of RES are defined to cover a number of levels of energy demand. First, required wind and photovoltaic power has been estimated together with the required sizes of PtG to completely decarbonize electrical generation and industrial CHP. These scenarios may be reached by installing RES capacities below the technical potential coupled with PtG capacities between 80 and 90 GW. The stored energy amounts to 17% of total primary energy consumption. Secondly, scenarios are modified to consider denuclearization of electrical system. Required installed RES power still does not surpass the technical potential but become extremely high and the economic feasibility should be further analysed. [ABSTRACT FROM AUTHOR]

Objectives To situate the current status of accreditation in four key international societies, ASPASP, FEPSAC, AASP, and ISSP, in a historical backdrop and then to draw on these approaches to propose future directions and developments relating to practical standards. Design A review of the origins and current status of accreditation in four international sport psychology societies is utilized to situate the recent prominence of professional standards and the importance of these in our global professional community. This review is written temporally from past, to present, to future prospects. Method A presentation of societal accreditation foci is situated temporally using the following structure: (a) emergence and historical backdrop from each society, (b) emergence and reasoning for accreditation, (c) current societal standards/status of accreditation, (d) future developments in the society's accreditation system, and (e) reflections and recommendations for global standards, with suggestions of how this might be accomplished. Results The presentation of scholarship is intended to serve as a form of advocacy for improved accreditation standards within the global professional community. The societal perspectives call for a balance between localized cultural infusion and proposed global guidelines upon which professionals might meet a converged reasonable practice threshold. Conclusions Sport psychology accreditation is increasingly important as the applied realm of this profession spans community physical activity/recreation, and developmental and elite/professional sport. Accredited practices must integrate universal and local approaches. [ABSTRACT FROM AUTHOR]

In Dakar and other urban centres in Senegal, young boys begging in the streets are commonly assumed to be talibés, or students of the Qur'an. This study intends to explore the boundaries of the discursive construction of talibés (who beg) in Senegal. 72 participants including Qur'anic teachers, staff and volunteers of international, national and local NGOs and associations, and representatives of state structures and international institutions, in Dakar, Rufisque and Saint Louis, Senegal. This qualitative study is based on doctoral field research conducted during the period of October 2017–July 2018. The main method of enquiry was semi-structured interviews and group discussions (n = 62), supplemented with observation and document review. The findings demonstrate the following themes: firstly, the category of talibé is often assumed to refer to those who beg, despite recognition that many children studying the Qur'an do not beg. Secondly, children who are assumed not to be learning the Qur'an are frequently still labelled as talibés. Thirdly, talibés who beg are differentiated from other boys who beg on the basis of assumptions of criminality (of others) and control (over talibés). Although talibé is understood to mean student of the Qur'an, those who beg all day and purportedly do not learn the Qur'an at all have come to be the dominant representation of a talibé used in development discourse. This has implications for the collection of data about these children as well as the interventions designed in response to this problematisation. [ABSTRACT FROM AUTHOR]

• Child protection system building in the Middle-East and North Africa is under-researched. • Lebanon's child protection system has undergone significant reform since 2015, moving towards a more integrated, procedural, and standardised model. • Unifying state, non-governmental, and religious stakeholders under one framework however remains challenging. • This paper recommends greater inclusion of community-based protection mechanisms and reengagement with religious family courts. Lebanon's fledgling child protection (CP) system has been criticised for being fragmented and overly crisis-driven to the detriment of the children served. This article conceptualises Lebanon's 'pluralistic' model and is the first to examine the contentious government reforms which have taken place since 2014. Drawing on 54 semi-structured stakeholder interviews, we examine how the state has wrested power from religious authorities, introduced national CP practice standards, and increased supervision of non-governmental services. This paper argues that these reforms have moved Lebanon further towards an integrated, legalistic and procedural CP approach. However, unresolved challenges remain to reconcile the competing roles, interests and capabilities of the state, the non-governmental sector, and religious authorities under one cohesive framework. This paper recommends strengthening support for the non-governmental sector, improving inclusion of community-based protection mechanisms, and reengagement with religious family courts to better meet the needs of children. The study not only has important implications for the development of Lebanon's protection system but also for the theories and practice debates surrounding system building in low and middle-income countries and the Middle-East and North African region. [ABSTRACT FROM AUTHOR]

International development assistance for health generates an emergent social network in which policy makers in recipient countries are connected to numerous bilateral and multilateral aid agencies and to other aid recipients. Ties in this global network are channels for the transmission of knowledge, norms and influence in addition to material resources, and policy makers in centrally situated governments receive information faster and are exposed to a more diverse range of sources and perspectives. Since diversity of perspectives improves problem-solving capacity, the structural position of aid-receiving governments in the health aid network can affect the health outcomes that those governments are able to attain. We apply a recently developed Social Network Analysis measure to health aid data for 1990–2010 to investigate the relationship between country centrality in the health aid network and improvements in child health. A generalized method of moments (GMM) analysis indicates that, controlling for the volume of health aid and other factors, higher centrality in the health aid network is associated with better child survival rates in a sample of 110 low and middle income countries. [ABSTRACT FROM AUTHOR]

Objective To explore the main sexual and reproductive health (SRH) issues for separated young migrants. Study design We conducted a rapid review. Methods The search for articles published between 2000 and June 2017 including peer-reviewed and 'grey' published literature from a range of databases including MEDLINE, AMED, Embase, ASSIA, Scopus, Web of Science and websites of international organisations (Missing Children Alliance, United Nations Population Fund (UNFPA), World Health Organization (WHO), United Nations Human Rights Council (UNHRC), Human Rights Watch, United Nations Children's Fund (UNICEF) and FBX Centre for Health and Human Rights) took place over 4 months. Themes emerging from the included studies and articles were synthesised. Results We found 44 articles from a range of countries of which 64% were peer-reviewed and 36% were from 'grey' literature. Structural violence and marginalisation were the key analytical themes that emerged and included young people's vulnerability to violence, unmet knowledge and service needs, barriers and stigma and poor SRH outcomes. Conclusions This is the first known review to summarise the key SRH issues for separated young migrants. As Europe hosts the greatest number of separated young people in recent history, their unique SRH concerns risk being overlooked. Public health practitioners and policy makers are encouraged to challenge the gaps that exist in their services. [ABSTRACT FROM AUTHOR]

Objectives interRAI launched this study to introduce a set of standardized self-report measures through which residents of long-term care facilities (LTCFs) could describe their quality of life and services. This article reports on the international development effort, describing measures relative to privacy, food, security, comfort, autonomy, respect, staff responsiveness, relationships with staff, friendships, and activities. First, we evaluated these items individually and then combined them in summary scales. Second, we examined how the summary scales related to whether the residents did or did not say that the LTCFs in which they lived felt like home. Design Cross-sectional self-report surveys by residents of LTCFs regarding their quality of life and services. Setting/Participants Resident self-report data came from 16,017 individuals who resided in 355 LTCFs. Of this total, 7113 were from the Flanders region of Belgium, 5143 residents were from Canada, and 3358 residents were from the eastern and mid-western United States. Smaller data sets were collected from facilities in Australia (20), the Czech Republic (72), Estonia (103), Poland (118), and South Africa (87). Measurements The interRAI Self-Report Quality of Life Survey for LTCFs was used to assess residents' quality of life and services. It includes 49 items. Each area of inquiry (eg, autonomy) is represented by multiple items; the item sets have been designed to elicit resident responses that could range from highly positive to highly negative. Each item has a 5-item response set that ranges from “never” to “always.” Results Typically, we scored individual items scored based on the 2 most positive categories: “sometimes” and “always.” When these 2 categories were aggregated, among the more positive items were: being alone when wished (83%); decide what clothes to wear (85%); get needed services (87%); and treated with dignity by staff (88%). Areas with a less positive response included: staff knows resident's life story (30%); resident has enjoyable things to do on weekends (32%); resident has people to do things with (33%); and resident has friendly conversation with staff (45%). We identified 5 reliable scales; these scales were positively associated with the resident statement that the LTCF felt like home. Finally, international score standards were established for the items and scales. Conclusions This study establishes a set of standardized, self-report items and scales with which to assess the quality of life and services for residents in LTCFs. The study also demonstrates that these scales are significantly related to resident perception of the home-like quality of the facilities. [ABSTRACT FROM AUTHOR]

Public care of abused and neglected children is one important element of statutory intervention which aims to address the major global challenge of protecting children from abuse and neglect. Where a child is part of a sibling group, this introduces particular challenges with regard to meeting the needs of all those affected. This paper presents findings from one of the first studies examining birth order effects on statutory intervention patterns for looked-after siblings. The experiences and outcomes of children were compared depending on maternal birth order at the time of data collection. We found strong evidence that the length of time from first referral of a child deemed at risk to first statutory intervention is greater for first-born than for last-born children and first-born children are significantly older than last-born children when they are first placed on statutory measures. The study concludes that first-born siblings may be particularly vulnerable to delayed statutory intervention and the cumulative effects of harm and certain routes to permanence may be less available to them. We argue for increased focus within international child welfare policy and practice on timely and intensive assessment of first-born children, where risk of maltreatment is identified, in order to address potential inequalities of access to protection. A focus on risk introduced by systemic factors within legal and welfare systems in addition to risk introduced by perpetrators of abuse is needed. We also argue for greater research attention to, and more precise measurement of, birth order as a variable in studies of the looked-after population. [ABSTRACT FROM AUTHOR]

Summary Foreign aid agencies represent and champion global development priorities within a donor nation. Increasingly however, these agencies sit within donor governments that are strongly committed to upholding the national interest through their development commitments. This paper is concerned with how bilateral aid agencies manage this tension and how they might continue to serve the altruistic aims of development. The main research question asks if autonomy—or a combination of autonomies—can improve a development agency’s ability to defend the humanitarian imperative of development against normative pressures privileging the national interest? By drawing on theories of autonomy within public management literatures, it is possible to identify points of leverage for development agencies where spaces for autonomous preferences and actions remain, as well as sources of limitation where such opportunities are considerably reduced. Six types of autonomy are examined across three nations widely perceived as strong performers as donors—Norway, the UK, and Sweden. The paper suggests that while structural autonomy is critical for preserving humanitarian motivations, there are also unexplored opportunities within other autonomous spheres. A multi-dimensional examination of autonomy highlights the varying capacity that development agencies have to resist pressures to strongly nationalize the global development project. [ABSTRACT FROM AUTHOR]

This essay offers a critical perspective on the prevailing language of 'learning crisis' and on the solutions widely promoted by international organisations (IOs) active in lower- and middle-income countries. Focusing specifically on pedagogical interventions, it sets out three cases: foundational learning; information technology; and systematic observation of teachers' classroom practice. Five questions frame the subsequent discussion: 1. What are the potential unintended effects of the language of crisis? 2. Do the understandings of pedagogy embedded in these measures reflect how teaching and learning function in different contexts? 3. In the quest for evidence, what evidence is being overlooked? 4. What are the risks of focusing interventions on literacy and numeracy, and their measurement? 5. What legitimacy do international actors have in defining and measuring quality pedagogy and prescribing interventions? [ABSTRACT FROM AUTHOR]

One of the major challenges in halting biodiversity loss is finding ways to address the issue in places where it would matter most; in the economic sectors of society that exert the strongest pressures on biodiversity such as agriculture, forestry and fisheries. Governments have acknowledged the need for this so termed mainstreaming under the Convention on Biological Diversity, but in practice have made little progress and struggle to find ways forward. In this paper we argue that the concept of mainstreaming was originally developed for situations where governments or intergovernmental organizations with explicit public mandates took the lead, but it is increasingly extended into various governance contexts where multiple types of actors at different levels (could) engage in conserving biodiversity. This paper aims to enable the identification of innovative repertoires of mainstreaming opportunities that optimally and realistically benefits from the broader governance context. Therefore it presents a framework, consisting of institutional, motivational and means dimensions for identifying key barriers and levers for mainstreaming biodiversity into economic sectors. By applying the framework on the forestry sector we show that it does not only help to identify new mainstreaming opportunities but it also shows directions for improving existing schemes as well. [ABSTRACT FROM AUTHOR]

Drawing on empirical ethnographic research conducted in three resettled areas in Nouakchott (Mauritania), our paper aims to enrich the debate on land formalization, attempting to understand the effects of slum upgrading programs and the titling process. In a context of securing land tenure as upheld by international institutions, the paper questions the implementation of these titling programs, which aim to deliver secure tenure and, more broadly, achieve economic development. It appeals for an analysis of how poor people react to titling policies in a context of highly complex relationships between formal and informal land status. Our case studies show that formal deeds do not necessarily lead to secure tenure. For the impoverished households who have withstood resettlements, these titling practices can be seen as a way to improve their livelihoods or, on the contrary, as breeding grounds for new forms of vulnerability. Moreover, these elements can also be perceived as triggers for encroachments between the State and the law and, at times, a reason to claim new rights. [ABSTRACT FROM AUTHOR]

This article reports the findings of a survey on end-of-life (EOL) care in nursing homes of 18 long-term care experts across 15 countries. The experts were chosen as a convenience-based sample of known experts in each country. The survey was administered in 2016 and included both open-ended responses for defining hospice care, palliative care, and “end of life,” and a series of questions related to the following areas—attitudes toward EOL care, current practice and EOL interventions, structure of care, and routine barriers. Overall experts strongly agreed that hospice and palliative care should be available in long-term care facilities and that both are defined by holistic, interdisciplinary approaches using measures of comfort across domains. However, it appears the experts felt that in most countries the reality fell short of what they believed would be ideal care. As a result, experts call for increased training, communication, and access to specialized EOL services within the nursing home. [ABSTRACT FROM AUTHOR]

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.Methods: In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m2 on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01852292, and is ongoing but no longer enrolling patients.Findings: Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5-5·3) in the buparlisib group and 3·5 months (2·2-3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45-0·95], nominal one-sided p=0·011). Grade 3-4 adverse events were reported in 62 (82%) of 76 patients in the buparlisib group and 56 (72%) of 78 patients in the placebo group. The most common grade 3-4 adverse events (occurring in ≥10% of patients in the buparlisib group vs the placebo group) were hyperglycaemia (17 [22%] of 76 vs two [3%] of 78), anaemia (14 [18%] vs nine [12%]), neutropenia (13 [17%] vs four [5%]), and fatigue (six [8%] vs eight [10%]). Serious adverse events (regardless of relation to study treatment) were reported for 43 (57%) of 76 patients in the buparlisib group and 37 (47%) of 78 in the placebo group. On-treatment deaths occurred in 15 (20%) of 76 patients in the buparlisib group and 17 (22%) of 78 patients in the placebo group; most were caused by disease progression and none were judged to be related to study treatment.Interpretation: On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding.Funding: Novartis Pharmaceuticals Corporation. [ABSTRACT FROM AUTHOR]

Background: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial. Here, we report the results of the secondary endpoint, health-related quality of life (HRQoL), of this trial.Methods: EORTC 18071 was a multinational, double-blind, randomised, phase 3 trial in patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) in 19 countries worldwide. Participants were randomly assigned (1:1) centrally by an interactive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region. HRQoL was assessed with the EORTC QLQ-C30 quality-of-life instrument at baseline, weeks 4, 7, 10, and 24, and every 12 weeks thereafter up to 2 years, irrespective of disease progression. Results were summarised by timepoint and in a longitudinal manner in the intention-to-treat population. Two summary scores were calculated for each HRQoL scale: the average score reported during induction (ipilimumab or placebo at a dose of 10 mg/kg, administered as one single dose at the start of days 1, 22, 43, and 64-ie, four doses in 3 weeks), and the average score reported after induction. A predefined threshold of a 10 point difference between arms was considered clinically relevant. The primary HRQoL endpoint was the global health scale, with the predefined hypothesis of no clinically relevant differences after induction between groups. This trial is registered with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168.Findings: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to treatment: 475 in the ipilimumab group and 476 in the placebo group. Compliance with completing the HRQoL questionnaire was 893 (94%) of 951 patients at baseline, 693 (75%) of 924 at week 24, and 354 (51%) of 697 at week 108. Patient mean global health scores during (77·32 [SD 17·36] vs 72·96 [17·82]; p=0·00011) and after induction (76·48 [17·52] vs 72·32 [18·60]; p=0·00067) were statistically significantly different between groups but were not clinically relevant. Mean global health scores differed most between the groups at week 7 (77 [SD 19] in the placebo group vs 72 [22] in the ipilimumab group) and week 10 (77 [20] vs 70 [23]). Mean HRQoL scores differed by more than 10 points at week 10 between treatment groups for diarrhoea (7·67 [SD 17·05] for placebo vs 18·17 [28·35] for ipilimumab) and insomnia (15·17 [22·53] vs 25·60 [29·19]).Interpretation: Despite increased toxicity, which led to treatment discontinuation for most patients during the induction phase of ipilimumab administration, overall HRQoL, as measured by the EORTC QLQ-C30, was similar between groups, as no clinically relevant differences (10 points or more) in global health status scores were observed during or after induction. Clinically relevant deterioration for some symptoms was observed at week 10, but after induction, no clinically relevant differences remained. Together with the primary analysis, results from this trial show that treatment with ipilimumab results in longer recurrence-free survival compared with that for treatment with placebo, with little impairment in HRQoL despite grade 3-4 investigator-reported adverse events.Funding: Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

The past several years have been a landmark moment for violence prevention, with renewed attention on the part of many international agencies, but especially the United Nations, with its adoption of the 2030 Agenda for Sustainable Development . The latter invites the world community to collaborate in an inclusive, long-ranging vision for the future, highlighting our interdependence and collective responsibility for humanity's future. A growing awareness that preventing violence does not just reduce death and disability but promotes creativity, economic growth, and general well-being is at the heart of this “movement”. An integration not only of the major disciplines but of various practical approaches is timely, and for this to occur, we require a broader overview of our existing societal structures. In this context, this fifteen article series modeled after a Global Health Studies course entitled, “Violence: Causes and Cures,” reviews the mechanisms that society has used in an attempt to stem violence. Following the article on public health, which has established that violence is preventable, this paper examines the approaches of global medicine, which begins with the local and human aspects of medical care. A model of compassion, altruism, respect, and encouragement is proposed for a person-centered, humanistic approach. Taking into account human suffering, principles of caregiving, cultural and religious sensitivity, and fostering of resilience and creativity is urgently needed in an increasingly globalizing world. [ABSTRACT FROM AUTHOR]

The importance of quality assurance in radiation therapy, as well as its positive consequences on patient treatment outcome, is well known to radiation therapy professionals. In low- and middle-income countries, the implementation of quality assurance in radiation therapy is especially challenging, due to a lack of staff training, a lack of national guidelines, a lack of quality assurance equipment and high patient daily throughput. According to the International Atomic Energy Agency (IAEA) Directory of Radiotherapy Centres, the proportion of linear accelerators compared with Co-60 machines has increased significantly in recent years in low- and middle-income countries. However, this increase in the proportion of relatively more demanding technology is not always accompanied with the necessary investment in staff training and quality assurance. The IAEA provides supports to low- and middle-income countries to develop and strengthen quality assurance programmes at institutional and national level. It also provides guidance, through its publications, on quality assurance and supports implementation of comprehensive clinical audits to identify gaps and makes recommendations for quality improvement in radiation therapy. The new AAPM TG100 report suggests a new approach to quality management in radiation therapy. If implemented, it will lead to improved cost-effectiveness of radiation therapy in all income settings. Low- and middle-income countries could greatly benefit from this new approach as it will help direct their scarce resources to areas where they can produce the optimum impact on patient care, without compromising patient safety. [ABSTRACT FROM AUTHOR]