Investigating the role of uncoupling of troponin I phosphorylation from changes in myofibrillar Ca(2+)-sensitivity in the pathogenesis of cardiomyopathy.

Contraction in the mammalian heart is controlled by the intracellular Ca2+ concentration as it is in all striated muscle, but the heart has an additional signalling system that comes into play to increase heart rate and cardiac output during exercise or stress. β-adrenergic stimulation of heart muscle cells leads to release of cyclic-AMP and the activation of protein kinase A which phosphorylates key proteins in the sarcolemma, sarcoplasmic reticulum and contractile apparatus. Troponin I (TnI) and Myosin Binding Protein C (MyBP-C) are the prime targets in the myofilaments. TnI phosphorylation lowers myofibrillar Ca2+-sensitivity and increases the speed of Ca2+-dissociation and relaxation (lusitropic effect).Recent studies have shown that this relationship between Ca2+-sensitivity and TnI phosphorylation may be unstable. In familial cardiomyopathies, both dilated and hypertrophic (DCM and HCM), a mutation in one of the proteins of the thin filament often results in the loss of the relationship (uncoupling) and blunting of the lusitropic response. For familial dilated cardiomyopathy in thin filament proteins it has been proposed that this uncoupling is causative of the phenotype. Uncoupling has also been found in human heart tissue from patients with hypertrophic obstructive cardiomyopathy as a secondary effect. Recently, it has been found that Ca2+-sensitizing drugs can promote uncoupling, whilst one Ca2+-desensitising drug Epigallocatechin 3-Gallate (EGCG) can reverse uncoupling.We will discuss recent findings about the role of uncoupling in the development of cardiomyopathies and the molecular mechanism of the process

Developing patient-centred care: an ethnographic study of patient perceptions and influence on quality improvement.

BACKGROUND: Understanding quality improvement from a patient perspective is important for delivering patient-centred care. Yet the ways patients define quality improvement remains unexplored with patients often excluded from improvement work. We examine how patients construct ideas of 'quality improvement' when collaborating with healthcare professionals in improvement work, and how they use these understandings when attempting to improve the quality of their local services. METHODS: We used in-depth interviews with 23 'patient participants' (patients involved in quality improvement work) and observations in several sites in London as part of a four-year ethnographic study of patient and public involvement (PPI) activities run by Collaborations for Leadership in Applied Health Research and Care for Northwest London. We took an iterative, thematic and discursive analytical approach. RESULTS: When patient participants tried to influence quality improvement or discussed different dimensions of quality improvement their accounts and actions frequently started with talk about improvement as dependent on collective action (e.g. multidisciplinary healthcare professionals and the public), but usually quickly shifted away from that towards a neoliberal discourse emphasising the role of individual patients. Neoliberal ideals about individual responsibility were taken up in their accounts moving them away from the idea of state and healthcare providers being held accountable for upholding patients' rights to quality care, and towards the idea of citizens needing to work on self-improvement. Participants portrayed themselves as governed by self-discipline and personal effort in their PPI work, and in doing so provided examples of how neoliberal appeals for self-regulation and self-determination also permeated their own identity positions. CONCLUSIONS: When including patient voices in measuring and defining 'quality', governments and public health practitioners should be aware of how neoliberal rationalities at the heart of policy and services may discourage consumers from claiming rights to quality care by contributing to public unwillingness to challenge the status quo in service provision. If the democratic potential of patient and public involvement initiatives is to be realised, it will be crucial to help citizens to engage critically with how neoliberal rationalities can undermine their abilities to demand quality care

Tackling Ultra-Poverty Through the Graduation Approach: Situating Sustainable Livelihoods in the Landscape of Social Protection and Safety Nets

BRAC was founded in Bangladesh in 1972 and now works in nine other countries with very impoverished populations: Afghanistan, Pakistan, Myanmar, Philippines, Uganda, Tanzania, South Sudan, Sierra Leone and Liberia. From its years of experience designing and implementing microfinance and other programs, BRAC gained the insight that a unique set of interventions is required to bring out of extreme poverty those who they, and now others, call the "ultra-poor": people living on half or less of a US $1.25-a-day poverty threshold. BRAC pioneered the approach in 2002 by combining social safety nets with support for income-generating, and named it the Graduation approach, or Targeting the Ultra Poor (TUP) program. Graduation programs complement small cash stipends and in-kind asset transfers with several other sequenced interventions including savings, training, social integration and health care services. Over the last decade the Consultative Group to Assist the Poor (CGAP), the Ford Foundation, and other donors have supported ten pilots across different continents which have been carefully analyzed, and in which over 75% of participants have met Graduation requirements. This paper summarizes the landscape and institutional context within which the Targeting the Ultra-poor program sits, in order to help BRAC and other organizations to expand its scale and encourage others to support and adopt this approach, thereby helping an additional one million families graduate from ultra-poverty by 2020

Seeking Shared Success: Business Model Innovation Through Mergers, Affiliations, and Alliances

Learn how alliances, affiliations, and mergers represent a path to enhanced sustainability and greater impact for community foundations. Hear perspectives from community foundation leaders, access tools for considering a new structure, and read case studies from six community foundations

Disclosure measurement in the empirical accounting literature: A review article

This is the first study to provide an extensive and critical review of different techniques used in the empirical accounting literature to measure disclosure. The purpose is to help future researchers to identify exemplars and to select suitable techniques or to develop their own techniques. It also provides in depth discussion of current measurement issues related to disclosure and identifies gaps in the current literature which future research may aim to cover