A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress

Cisplatin and its platinum analogs, carboplatin and oxaliplatin, are some of the most widely used cancer chemotherapeutics. Although cisplatin and carboplatin are used primarily in germ cell, breast and lung malignancies, oxaliplatin is instead used almost exclusively to treat colorectal and other gastrointestinal cancers. Here we utilize a unique, multi-platform genetic approach to study the mechanism of action of these clinically established platinum anti-cancer agents, as well as more recently developed cisplatin analogs. We show that oxaliplatin, unlike cisplatin and carboplatin, does not kill cells through the DNA-damage response. Rather, oxaliplatin kills cells by inducing ribosome biogenesis stress. This difference in drug mechanism explains the distinct clinical implementation of oxaliplatin relative to cisplatin, and it might enable mechanistically informed selection of distinct platinum drugs for distinct malignancies. These data highlight the functional diversity of core components of front-line cancer therapy and the potential benefits of applying a mechanism-based rationale to the use of our current arsenal of anti-cancer drugs

Understanding staff perspectives of quality in practice in healthcare

BACKGROUND: Extensive work has been focussed on developing and analysing different performance and quality measures in health services. However less has been published on how practitioners understand and assess performance and the quality of care in routine practice. This paper explores how health service staff understand and assess their own performance and quality of their day to day work. Asking staff how they knew they were doing a good job, it explored the values, motivations and behaviours of staff in relation to healthcare performance. The paper illustrates how staff perceptions of quality and performance are often based on different logics to the dominant notions of performance and quality embedded in current policy. METHODS: Using grounded theory and qualitative, in-depth interviews this research studied how primary care staff understood and assessed their own performance and quality in everyday practice. 21 people were interviewed, comprising of health visitors, occupational therapists, managers, human resources staff and administrators. Analytic themes were developed using open and axial coding. RESULTS: Diverse aspects of quality and performance in healthcare are rooted in differing organisational logics. Staff values and personal and professional standards are an essential element in understanding how quality is co-produced in everyday service interactions. Tensions can exist between patient centred, relational care and the pressures of efficiency and rationalisation. CONCLUSIONS: Understanding the perspectives of staff in relation to how quality in practice develops helps us to reflect on different mechanisms to manage quality. Quality in everyday practice relies upon staff values, motivations and behaviours and how staff interact with patients, putting both explicit and tacit knowledge into specific action. However organisational systems that manage quality often operate on the basis of rational measurement. These do not always incorporate the intangible, relational and tacit dimensions of care. Management models need to account for these relational and experiential aspects of care quality to support the prioritisation of patients’ needs. Services management, knowledge management and ethics of care literature can provide stronger theoretical building blocks to understand how to manage quality in practice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12913-015-0788-1) contains supplementary material, which is available to authorized users

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions

People, place, and system: organizations and the renewal of urban social theory

This article offers a theoretical framework for thinking about how organizations matter for the production, reproduction, and amelioration of urban poverty. We draw on the classical concept of integration, in both its social and systemic versions, as an important tool for advancing urban social theory. A key challenge for urban organizational analysts is to keep within view the processes of both social and systemic integration, while empirically investigating how they are connected (or not). Too many urban researchers focus on one or the other, with little conceptualization of the importance of linking the two. We argue that urban organizations of all kinds provide a strategic site for observing processes of both social and systemic integration, and that urban organizational research should examine many of them to better understand the multiple urban transformations currently in process