A Kir6.2 mutation causing severe functional effects in vitro produces neonatal diabetes without the expected neurological complications

AIMS/HYPOTHESIS: Heterozygous activating mutations in the pancreatic ATP-sensitive K+ channel cause permanent neonatal diabetes mellitus (PNDM). This results from a decrease in the ability of ATP to close the channel, which thereby suppresses insulin secretion. PNDM mutations that cause a severe reduction in ATP inhibition may produce additional symptoms such as developmental delay and epilepsy. We identified a heterozygous mutation (L164P) in the pore-forming (Kir6.2) subunit of the channel in three unrelated patients and examined its functional effects. METHODS: The patients (currently aged 2, 8 and 20 years) developed diabetes shortly after birth. The two younger patients attempted transfer to sulfonylurea therapy but were unsuccessful (up to 1.1 mg kg(-1) day(-1)). They remain insulin dependent. None of the patients displayed neurological symptoms. Functional properties of wild-type and mutant channels were examined by electrophysiology in Xenopus oocytes. RESULTS: Heterozygous (het) and homozygous L164P K(ATP) channels showed a marked reduction in channel inhibition by ATP. Consistent with its predicted location within the pore, L164P enhanced the channel open state, which explains the reduction in ATP sensitivity. HetL164P currents exhibited greatly increased whole-cell currents that were unaffected by sulfonylureas. This explains the inability of sulfonylureas to ameliorate the diabetes of affected patients. CONCLUSIONS/INTERPRETATION: Our results provide the first demonstration that mutations such as L164P, which produce a severe reduction in ATP sensitivity, do not inevitably cause developmental delay or neurological problems. However, the neonatal diabetes of these patients is unresponsive to sulfonylurea therapy. Functional analysis of PNDM mutations can predict the sulfonylurea response

The economic case for prioritizing governance over financial incentives in REDD+

This article contributes to the ongoing debate on the role of public policies and financial incentives in Reducing Emissions from Deforestation and forest Degradation (REDD+). It argues that the subordination of policies to results-based payments for emission reductions causes severe economic inefficiencies affecting the opportunity cost, transaction cost and economic rent of the programme. Such problems can be addressed by establishing sound procedural, land and financial governance at the national level, before REDD+ economic incentives are delivered at scale. Consideration is given to each governance dimension, the entry points for policy intervention and the impact on costs. International support must consider the financial and political cost of governance reforms, and use a pay-for-results ethos based on output and outcome indicators. This can be done in the readiness process but only if the latter’s legal force, scope, magnitude and time horizon are adequately reconsidered. In sum, the paper provides ammunition for the institutionalist argument that UNFCCC Parties must prioritise governance reform between now and the entry into force of the new climate agreement in 2020, and specific recommendations about how this can be done: only by doing so will they create the basis for the programme’s financial sustainability

Towards the Development of an Empirical Model for Islamic Corporate Social Responsibility: Evidence from the Middle East

Academic research suggests that variances in contextual dynamics, and more specifically religion, may lead to disparate perceptions and practices of corporate social responsibility (CSR). Driven by the increased geopolitical and economic importance of the Middle East and identified gaps in knowledge, the study aims to examine if indeed there is a divergent form of CSR exercised in the region. The study identifies unique CSR dimensions and constructs presented through an empirical framework in order to outline the practice and perception of CSR in a context with strong Islamic beliefs. The framework goes beyond the platform of mere Islamic philanthropy and is based on CSR-stakeholder management practices. Following an exploratory research design and collecting interview data from representatives of 63 organisations from Saudi Arabia, the United Arab Emirates and Oman, the study offers a snapshot of the CSR reality from the perspective of those living the phenomenon. The results suggest that the practice and perception of CSR in the examined context are largely grounded in the areas of social and altruistic actions but they cannot be examined in isolation from the religious context of CSR operation. This focus is mainly attributed to the dominant role of Islam in the examined sample, which leads to forms of non-structured or semi-structured approaches to CSR. Apart from the theoretical advancements offered to the CSR literature, the study also provides contributions for practitioners and policy makers.</p

Multinationals’ Accountability on Sustainability: The Evolution of Third-party Assurance of Sustainability Reports

In this article we explore how multinational corporations (MNCs) adopt assurance practices to develop and sustain organizational accountability for sustainability. Using a panel of Fortune Global 250 firms over a period of 10 years, we document the diffusion patterns of third-party assurance of sustainability reports. We specifically investigate how evolving auditing practices, namely diversity of assurance standards and type of assurance providers, shape the quality of sustainability assurance statements. The results illustrate great variability in the adoption of assurance practices in the formative stages of this novel market. Our descriptive analysis indicates the relevance of external institutional pressures as well as internal resources and capabilities as underlying factors driving the adoption of assurance. Our evidence also suggests that several MNCs project a decoupled or symbolic image of accountability through assurance, thereby undermining the credibility of these verification practices. The paper contributes to the emerging literature on international accountability standards and emphasizes the need to enhance theory-based, cross-disciplinary knowledge related to auditing and accountability processes for sustainability

On the Role of Faith in Sustainability Management: A Conceptual Model and Research Agenda

International audienceThe objective of this article is to develop a faith development perspective on corporate sustainability. A firm’s management of sustainability is arguably determined by the way decision-makers relate to the other and the natural environment, and this relationship is fundamentally shaped by faith. This study advances theoretical understanding of the approach managers take on sustainability issues by explaining how four distinct phases of faith development—improvidence, obedience, irreverence and providence—determine a manager’s disposition towards sustainability. Combining insights from intentional and relational faith development theories, the analysis reveals that a manager’s faith disposition can be measured according to four interrelated process criteria: (1) connectivity as a measure of a manager’s actual engagement and activities aimed at relating to sustainability; (2) inclusivity as a measure of who and what is included or excluded in a manager’s moral consideration; (3) emotional affinity as a measure of a manager’s sensitivity and affection towards the well-being of others and ecological welfare; and (4) reciprocity as a measure of the degree to which a manager is rewarded for responding to the needs and concerns of ‘Others’, mainly in the form of a positive emotional (and relational) stimulus. The conceptual model consolidates earlier scholarly works on the psychological drivers of sustainability management by illuminating our search for a process of faith development that connects with an increasingly complex understanding of the role of business in society