Regulation of Adipocyte Transcription by PPARgamma Ligands

Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for PPARgamma, the adipocyte-predominant nuclear receptor (NR). The classic model of NR action, involving binding of ligand to the NR on DNA, explains positive regulation of gene expression, but both ligand-dependent transcriptional repression and indirect regulation are not well understood. We have addressed these issues by studying the direct effects of rosiglitazone on gene transcription, using global run-on sequencing (GRO-seq). Rosi-induced changes in gene body transcription were pronounced after 10 minutes and correlated with steady-state mRNA levels as well as with transcription at nearby enhancers (eRNAs). Up-regulated eRNAs occurred almost exclusively at PPARg binding sites, to which rosi treatment recruited coactivators including MED1, p300, and CBP, without changes in binding of the corepressor NCoR. By contrast, down-regulated eRNAs fell in sites devoid of PPARg but enriched for a variety of other TFs in the C/EBP and AP-1 families. These enhancers lost coactivator binding upon rosi treatment, suggesting that rosi treatment causes redistribution of coactivators to PPARg sites and away from enhancers containing other TFs, leading to transcriptional repression at these eRNAs and their target genes. We also investigated the function of MRL-24, a compound that has been shown to lack PPARg transactivation activity and regulate a distinct subset of PPARg target genes while functioning as an equally effective insulin sensitizer as rosi. Though our goal was to identify whether MRL-24 regulates the same functional enhancers marked by eRNAs as rosi, we instead found that MRL-24 does not control a distinct subset of target genes, but rather acts as a partial agonist for PPARg. Together, these studies further our understanding of transcriptional regulation by modulation of PPARg activity, including insights into determining functional enhancers and mechanisms of transcriptional repression by activation of a NR

Dynamic Quality of Service in Software-Defined Networks

Quality of service is a necessary function of today’s networks. A proper quality of service ensures that packets are delivered effectively and fast. In traditional networks, quality of service has to be manually configured on each piece of hardware in the network. This manual procedure makes the process of implementing a quality of service in a network costly. Not to mention, if part of the configuration is incorrect, or a mistake is made during the configuration, everything must be corrected on each piece of affected hardware. In this paper, I will be exploring the effect of using a software-defined network controller and a quality of service to handle certain flows of traffic in a network. The main tool used is the OpenFlow defined queue. Queues and flow rules will allow a switch to control individual flows and the network resources that each flow consumes. Factors that will be explored are the bandwidth usage of a flow and the time taken by the network to implement new flow rules. While bandwidth usage is taken into account in traditional networks, changing a quality of service is a new dynamic

A safer place for patients: learning to improve patient safety

1 Every day over one million people are treated successfully by National Health Service (NHS) acute, ambulance and mental health trusts. However, healthcare relies on a range of complex interactions of people, skills, technologies and drugs, and sometimes things do go wrong. For most countries, patient safety is now the key issue in healthcare quality and risk management. The Department of Health (the Department) estimates that one in ten patients admitted to NHS hospitals will be unintentionally harmed, a rate similar to other developed countries. Around 50 per cent of these patient safety incidentsa could have been avoided, if only lessons from previous incidents had been learned. 2 There are numerous stakeholders with a role in keeping patients safe in the NHS, many of whom require trusts to report details of patient safety incidents and near misses to them (Figure 2). However, a number of previous National Audit Office reports have highlighted concerns that the NHS has limited information on the extent and impact of clinical and non-clinical incidents and trusts need to learn from these incidents and share good practice across the NHS more effectively (Appendix 1). 3 In 2000, the Chief Medical Officer’s report An organisation with a memory 1 , identified that the key barriers to reducing the number of patient safety incidents were an organisational culture that inhibited reporting and the lack of a cohesive national system for identifying and sharing lessons learnt. 4 In response, the Department published Building a safer NHS for patients3 detailing plans and a timetable for promoting patient safety. The goal was to encourage improvements in reporting and learning through the development of a new mandatory national reporting scheme for patient safety incidents and near misses. Central to the plan was establishing the National Patient Safety Agency to improve patient safety by reducing the risk of harm through error. The National Patient Safety Agency was expected to: collect and analyse information; assimilate other safety-related information from a variety of existing reporting systems; learn lessons and produce solutions. 5 We therefore examined whether the NHS has been successful in improving the patient safety culture, encouraging reporting and learning from patient safety incidents. Key parts of our approach were a census of 267 NHS acute, ambulance and mental health trusts in Autumn 2004, followed by a re-survey in August 2005 and an omnibus survey of patients (Appendix 2). We also reviewed practices in other industries (Appendix 3) and international healthcare systems (Appendix 4), and the National Patient Safety Agency’s progress in developing its National Reporting and Learning System (Appendix 5) and other related activities (Appendix 6). 6 An organisation with a memory1 was an important milestone in the NHS’s patient safety agenda and marked the drive to improve reporting and learning. At the local level the vast majority of trusts have developed a predominantly open and fair reporting culture but with pockets of blame and scope to improve their strategies for sharing good practice. Indeed in our re-survey we found that local performance had continued to improve with more trusts reporting having an open and fair reporting culture, more trusts with open reporting systems and improvements in perceptions of the levels of under-reporting. At the national level, progress on developing the national reporting system for learning has been slower than set out in the Department’s strategy of 2001 3 and there is a need to improve evaluation and sharing of lessons and solutions by all organisations with a stake in patient safety. There is also no clear system for monitoring that lessons are learned at the local level. Specifically: a The safety culture within trusts is improving, driven largely by the Department’s clinical governance initiative 4 and the development of more effective risk management systems in response to incentives under initiatives such as the NHS Litigation Authority’s Clinical Negligence Scheme for Trusts (Appendix 7). However, trusts are still predominantly reactive in their response to patient safety issues and parts of some organisations still operate a blame culture. b All trusts have established effective reporting systems at the local level, although under-reporting remains a problem within some groups of staff, types of incidents and near misses. The National Patient Safety Agency did not develop and roll out the National Reporting and Learning System by December 2002 as originally envisaged. All trusts were linked to the system by 31 December 2004. By August 2005, at least 35 trusts still had not submitted any data to the National Reporting and Learning System. c Most trusts pointed to specific improvements derived from lessons learnt from their local incident reporting systems, but these are still not widely promulgated, either within or between trusts. The National Patient Safety Agency has provided only limited feedback to trusts of evidence-based solutions or actions derived from the national reporting system. It published its first feedback report from the Patient Safety Observatory in July 2005

Second consultation on developing standards for identifying evidence-based practices in reproductive health

The STEP UP consortium and the High Impact Practices initiative, together with other partners, supported three consultation meetings to inform the use of appropriate standards of evidence for recommending best practices in reproductive health (RH). The second consultation, reported here, brought together researchers and funders to review the research designs and methodologies that can be used to generate evidence on the impact of FP/RH interventions and on their implementation; the mechanisms and structures through which such evidence is reviewed and translated into recommendations; and the implications for organizing and funding evidence generation to maximize its quality and utility. Drawing from the presentations, three plenary discussions were held which reflected a diversity of views on what constitutes high-quality evidence, which type of evidence is appropriate for which type of recommendations, and which approaches should be followed to translate evidence into practice recommendations. Recommendations for consolidating standards of evidence and formulating guidelines for high-impact practices in FP/RH programming and policymaking are presented in this report

Measuring the impact of contraceptive use on unintended pregnancy and other health outcomes

This brief describes several statistical models that have been developed to estimate the number of health outcomes that will be averted because of contraceptive use. Concerns have been expressed that this range of approaches—which overlap in the impacts they estimate, but sometimes use different inputs, mathematical algorithms, and assumptions, and may produce different results—may be confusing for policymakers, managers, and donors who want to measure or evaluate these impacts. To address these concerns, the STEP UP consortium convened two expert meetings to review the estimation methods used; come to consensus on methodologies and assumptions, where possible; and provide guidance to those wanting to measure such impacts. As a result of this consensus-building process, decisionmakers and managers using the different models can more clearly understand the assumptions behind each model so as to make informed choices between them

Village of Cuba St. Francis of Assisi Park Improvement Plan Community Input Report

At the request of the Village of Cuba Council, Healthy Kids, Healthy Cuba and Step into Cuba have gathered additional community input regarding the proposed improvements to the Village of Cuba St Francis of Assisi Park. Previously, we had obtained community input through a series of meetings held in Cuba. Chance Munns, a landscape architect working with the University of New Mexico Prevention Research Center, developed the community ideas into three maps with descriptions of the proposed improvements. At the request of the Village Council last fall, we obtained additional input from the Cuba community on the Park improvement plan via a mobile display placed throughout Cuba in the Spring and Summer of 2012

Leveraging Health Behavior and Communication Theories to Support Adolescent and Young Adults: Conceptualizing Social Media Wellness in Relation to Disordered Eating

Social media platforms like Instagram serve as an important mechanism for transmitting social information and influence. However, the nature and use of these platforms are known to perpetuate eating disorders (EDs) or further disorder eating symptoms. This concept paper proposes merging health behavior and communication theory to create a comprehensive and applicable framework for remediating pro-eating disorder social media content among people who have eating disorders. To this end, the Social Media Wellness Model, which is adapted from the Health Belief Model, the Uses and Gratifications approach, the MAIN model of media affordances, and media literacy training, is proposed. This paper shows how theoretical model components can be mapped back to behaviors typified by individuals with EDs, or those predisposed to developing EDs. Subsequently, we propose a training intervention to highlight salient literacy cues, and outline next steps for testing and developing this model with the ongoing support of a community advisory board (CAB). Creating a CAB with individuals who have lived experience of an ED or disordered eating, and who use social media, will be vital to testing the applicability of this conceptual Social Media Wellness Model for ED recovery

The consumer perspective: A consultation with senior health officials from developing countries on standards of evidence for reproductive and maternal health care

The Population Council (through the STEP UP consortium and the Evidence Project) and the High Impact Practices (HIP) Collaboration, together with other partners, held a series of three consultative meetings around the topic of standards of evidence in reproductive and maternal health. This report details the third and final meeting held in Bellagio, Italy in February 2016. The meeting brought together developing-country decisionmakers to vet, from the research “consumer” perspective, the recommendations that emerged from the second consultation and to elicit further recommendations on how to better generate and package evidence to meet the needs of decisionmakers. Also in attendance were donors, multilateral organizations, and researchers from the second consultation, so that they could better understand the decisionmakers’ perspectives and forge connections between “producers” and “consumers” of evidence