environmental change as driver for sustainable business behaviour

Business is often viewed as a main culprit for environmental deterioration and thus as a major cause for environmental change, due to pollution impacts or the over-abstraction and exploitation of environmental resources in response to short-termed profit-maximizing interests. At the same time, business is increasingly affected by environmental change as well and thus faced with the need to develop strategies to cope and adapt. A much quoted example in this regard is the increasing scarcity of production-relevant resources, such as water in case of the food and beverage industries. This not only highlights the dependence of economic viability and stability on sound and resilient ecosystems, but also gives rise to the question of how the potentially growing awareness of business’ vulnerability to environmental change can be used in order to change corporate motivational patterns, leading to more responsible and sustainable business practices. This question is of particular interest in countries with weak regulatory capacities, as government might not be in a position to provide sufficient regulatory incentives. Evidence from South African business sectors indicates that firms’ self motivation to engage in sustainable practices can be leveraged and modulated by governmental as well as other actors through engaging governance modes to yield sustainable outcomes. The results however also convey necessary conditions in terms of government will and capacity, particularly with regards to skills required for engaging a broad range of societal actors. The degree to which business behaviour can be transformed crucially depends on these factors particularly at the local governance level.Draft versio

translating international discourse to local realities

The international discourse on sustainable development has matured over the past 20 years and taken on myopia of different forms and interpretations. A core requirement of the Rio Agenda is the development of national strategies for sustainable development. While industrialised countries have in many cases undertaken the effort of designing comprehensive strategies to guide sustainable development at the national level, middle-income countries and particularly developing nations struggle even with the process requirements of designing such strategies. This paper aims to shed light on several aspects of the uptake of the sustainable development discourse in middle-income and developing countries. Comparing the situation in South Africa and Kenya, challenges, stumbling blocks as well as favouring conditions for the acceptance of international sustainability discourses into national policy frameworks are identified. Specifically, the analysis assesses the impact of international norms on national policies in the areas of environmental and social protection. Since not only governmental but also non-governmental actors are receptive to the international sustainability discourse, the analysis is augmented by taking into account the contribution and transformative power of other societal actors. The findings demonstrate that non-governmental in fact support transformative processes towards adopting sustainability policies. Similarly conducive are international capacity- building and facilitation efforts. The eventual adoption however depends on the willingness and capacity of national government actors.Draft versio

What Makes Cross-Sector Partnerships Successful? A Comparative Case Study Analysis of Diverse Partnership Types in an Emerging Economy Context

This paper seeks to identify leadership success factors of cross-sector partnerships. We start with an overview of relevant scholarly and practice-oriented work, and motivate our research with reference to the need to add nuance to existing constructs, to explicitly consider the implications of different partnership types, and to assess the role of socio-economic and other contextual factors in an emerging economy. Our methodology focuses on ten comparative case studies, premised on two intermediate steps to develop a typology and evaluative criteria for partnerships

the case of South Africa

Das Engagement und somit auch der Einfluss multinationaler Firmen in Entwicklungs- und Schwellenländern sind oftmals umstritten. In Hinblick auf umweltschädliche Auswirkungen gibt es vielfältige Belege dafür, dass Firmen schwache staatliche Regulierung im Umweltbereich ausnutzen; häufig mit verheerenden Folgen. Im Rahmen von freiwilligen CSR-Standards sind in letzter Zeit zunehmend Anstrengungen unternommen worden, um solchen Entwicklungen entgegenzuwirken. In unserer Recherche untersuchen wir das Wechselspiel freiwilliger CSRNormen mit öffentlicher Regulierung in Ländern begrenzter Staatlichkeit. Wir gehen dabei von folgender Frage aus: Fördern multinationale Unternehmen, die sich zu internationalen CSR-Normen verpflichtet haben, diese Standards auch aktiv in den Ländern, in denen sie operieren? Anhand der Situation im Bereich Umweltpolitik in Südafrika und beispielhaft anhand der Bergbau-, und Lebensmittelindustrie sollen zwei Fragen beantwortet werden: Erstens, bringen sich Firmen, die freiwillige Umweltstandards unterzeichnet haben, aktiv in die Förderung kollektiver Umweltregulierung ein und unter welchen Bedingungen? Und zweitens, falls sie dies tun, welche Modelle setzen sich durch: engagieren sich Firmen durch Einflussnahme auf den Staat, durch private Selbstregulierung oder in Formen öffentlich-privater Koregulierung

Skin TLR7 triggering promotes accumulation of respiratory dendritic cells and natural killer cells.

The TLR7 agonist imiquimod has been used successfully as adjuvant for skin treatment of virus-associated warts and basal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo-controlled experimental animal study we have used multicolour flow cytometry to systematically analyze the modulation of respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimod significantly increased respiratory dendritic cells (DC) and natural killer cells, whereas total respiratory leukocyte, alveolar macrophages, classical CD4+ T helper and CD8+ T killer cell numbers were not or only moderately affected. DC subpopulation analyses revealed that elevation of respiratory DC was caused by an increase of respiratory monocytic DC and CD11b(hi) DC subsets. Lymphocyte subpopulation analyses indicated a marked elevation of respiratory natural killer cells and a significant reduction of B lymphocytes. Analysis of cytokine responses of respiratory leukocytes after stimulation with Klebsiella pneumonia indicated reduced IFN-γ and TNF-α expression and increased IL-10 and IL-12p70 production after 7 day low dose skin TLR7 triggering. Additionally, respiratory NK cytotoxic activity was increased after 7d skin TLR7 triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stimulation modulated respiratory leukocyte composition without inducing overt pulmonary inflammation. These data suggest the possibility to modulate respiratory leukocyte composition and respiratory cytokine responses against pathogens like Klebsiella pneumonia through skin administration of a clinically approved TLR7 ligand. Skin administration of synthetic TLR7 ligands may represent a novel, noninvasive means to modulate respiratory immunity

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses

Invading Basement Membrane Matrix Is Sufficient for MDA-MB-231 Breast Cancer Cells to Develop a Stable In Vivo Metastatic Phenotype

1 - ArticleIntroduction: The poor efficacy of various anti-cancer treatments against metastatic cells has focused attention on the role of tumor microenvironment in cancer progression. To understand the contribution of the extracellular matrix (ECM) environment to this phenomenon, we isolated ECM surrogate invading cell populations from MDA-MB-231 breast cancer cells and studied their genotype and malignant phenotype. Methods: We isolated invasive subpopulations (INV) from non invasive populations (REF) using a 2D-Matrigel assay, a surrogate of basal membrane passage. INV and REF populations were investigated by microarray assay and for their capacities to adhere, invade and transmigrate in vitro, and to form metastases in nude mice. Results: REF and INV subpopulations were stable in culture and present different transcriptome profiles. INV cells were characterized by reduced expression of cell adhesion and cell-cell junction genes (44% of down regulated genes) and by a gain in expression of anti-apoptotic and pro-angiogenic gene sets. In line with this observation, in vitro INV cells showed reduced adhesion and increased motility through endothelial monolayers and fibronectin. When injected into the circulation, INV cells induced metastases formation, and reduced injected mice survival by up to 80% as compared to REF cells. In nude mice, INV xenografts grew rapidly inducing vessel formation and displaying resistance to apoptosis. Conclusion: Our findings reveal that the in vitro ECM microenvironment per se was sufficient to select for tumor cells with a stable metastatic phenotype in vivo characterized by loss of adhesion molecules expression and induction of proangiogenic and survival factors

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Effects of a Shortened Depreciation Schedule on the Investment Costs for Combined Heat and Power Systems, Working Paper

Abstract We investigate and compare several generic depreciation methods to assess the effectiveness of possible policy measures with respect to the depreciation schedules for investments in combined heat and power plants in the United States. We assess the different depreciation methods for CHP projects of various sizes (ranging from 1 MW to 100 MW). We evaluate the impact of different depreciation schedules on the tax shield, and the resulting tax savings to potential investors. We show that a shorter depreciation cycle could have a substantial impact on the cost of producing power, making cogeneration more attractive. The savings amount to approximately 6-7% of capital and fixed operation and maintenance costs, when changing from the current system to a 7 year depreciation scheme with switchover from declining balance to straight line depreciation. Suggestions for further research to improve the analysis are given. 3