Are High Wage Jobs Hazardous to Your Health? The Myth That Attracting Higher Paying Extractive Industry Jobs Is a Desirable Community Economic Development Strategy

Community/Rural/Urban Development,

Dioxin and immune regulation: Emerging role of aryl hydrocarbon receptor in the generation of regulatory T cells

The immune toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to as dioxin, has been studied for over 35 years but only recently has the profound immune suppression induced by TCDD exposure been linked to induction of regulatory T cells (Tregs). The effects of TCDD are mediated through its binding to the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. The subsequent AHR-dependent effects on immune responses are determined by the cell types involved, their activation status, and the type of antigenic stimulus. Collectively, studies indicate that TCDD inhibits CD4⁺ T cell differentiation into T helper (Th)1, Th2, and Th17 effector cells, while inducing Foxp3-negative and/or preserving Foxp3⁺ Tregs. Although it is not yet clear how activation of AHR by TCDD induces Tregs, there is a potential therapeutic role for alternative AHR ligands in the treatment of immune-mediated disorders.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The article is copyrighted by the New York Academy of Sciences and published by John Wiley & Sons Ltd. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291749-6632.Keywords: Aryl hydrocarbon receptor, Regulatory T cells, Foxp3, 2\, 3\, 7\, 8 tetrachlorodibenzo-p-dioxin, NF-κB, Dendritic cells, Indoleamine 2\, 3-dioxygenas

How host organizations prepare for and learn from expatriate assignments

© 2019 Wiley Periodicals, Inc. This article reveals what goes on inside host organizations prior to and during expatriate assignments. On the basis of analyzing organizational documents and conducting 43 interviews with host country nationals (HCNs) and expatriates in 30 Vietnamese organizations that host external foreign assignments, we provide a detailed account of HCNs' experiences and unearth sophisticated preparation and management activities designed to maximize these organizations' learning. We depict what we call “a host organization lifecycle” and extract five lessons: (a) host organizations prepare carefully in advance to learn as much as possible from expatriates; (b) HCNs experience quite dramatic adjustments and burdens during expatriates' placements; (c) mutual trust between expatriates and HCNs is a prerequisite for HCNs' learning; (d) most of HCNs' learning occurs informally via interactions with expatriates or observing how they work; (e) host organization managers actively manage HCN–expatriate relationships. Our findings outline a “wish list” of practices that expatriate-using organizations could consider deploying for expatriate assignments that focus on the benefit of the host organization' development

The Prospects for Payment for Ecosystem Services (PES) in Vietnam: A Look at Three Payment Schemes

Global conservation discourses and practices increasingly rely on market-based solutions to fulfill the dual objective of forest conservation and economic development. Although varied, these interventions are premised on the assumption that natural resources are most effectively managed and preserved while benefiting livelihoods if the market-incentives of a liberalised economy are correctly in place. By examining three nationally supported payment for ecosystem service (PES) schemes in Vietnam we show how insecure land tenure, high transaction costs and high opportunity costs can undermine the long-term benefits of PES programmes for local households and, hence, potentially threaten their livelihood viability. In many cases, the income from PES programmes does not reach the poor because of political and economic constraints. Local elite capture of PES benefits through the monopolization of access to forestland and existing state forestry management are identified as key problems. We argue that as PES schemes create a market for ecosystem services, such markets must be understood not simply as bald economic exchanges between ‘rational actors’ but rather as exchanges embedded in particular socio-political and historical contexts to support the sustainable use of forest resources and local livelihoods in Vietnam

Assessment of the quality of recommendations from 161 clinical practice guidelines using the Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX) instrument shows there is room for improvement

To assess the quality of recommendations from 161 clinical practice guidelines (CPGs) using AGREE-REX-D (Appraisal of Guidelines REsearch and Evaluation-Recommendations Excellence Draft). International CPG community. Three hundred twenty-two international CPG developers, users, and researchers. Participants were assigned to appraise one of 161 CPGs selected for the study using the AGREE-REX-D tool Main outcome measures: AGREE-REX-D scores of 161 CPGs (7-point scale, maximum 7). Recommendations from 161 CPGs were appraised by 322 participants using the AGREE-REX-D. CPGs were developed by 67 different organizations. The total overall average score of the CPG recommendations was 4.23 (standard deviation (SD) = 1.14). AGREE-REX-D items that scored the highest were (mean; SD): evidence (5.51; 1.14), clinical relevance (5.95; SD 0.8), and patients/population relevance (4.87; SD 1.33), while the lowest scores were observed for the policy values (3.44; SD 1.53), local applicability (3,56; SD 1.47), and resources, tools, and capacity (3.49; SD 1.44) items. CPGs developed by government-supported organizations and developed in the UK and Canada had significantly higher recommendation quality scores with the AGREE-REX-D tool (p < 0.05) than their comparators. We found that there is significant room for improvement of some CPGs such as the considerations of patient/population values, policy values, local applicability and resources, tools, and capacity. These findings may be considered a baseline upon which to measure future improvements in the quality of CPGs

Development and Validation of a Tool to Assess the Quality of Clinical Practice Guideline Recommendations

Clinical practice guidelines (CPGs) may lack rigor and suitability to the setting in which they are to be applied. Methods to yield clinical practice guideline recommendations that are credible and implementable remain to be determined. To describe the development of AGREE-REX (Appraisal of Guidelines Research and Evaluation-Recommendations Excellence), a tool designed to evaluate the quality of clinical practice guideline recommendations. A cross-sectional study of 322 international stakeholders representing CPG developers, users, and researchers was conducted between December 2015 and March 2019. Advertisements to participate were distributed through professional organizations as well as through the AGREE Enterprise social media accounts and their registered users. Between 2015 and 2017, participants appraised 1 of 161 CPGs using the Draft AGREE-REX tool and completed the AGREE-REX Usability Survey. Usability and measurement properties of the tool were assessed with 7-point scales (1 indicating strong disagreement and 7 indicating strong agreement). Internal consistency of items was assessed with the Cronbach, and the Spearman-Brown reliability adjustment was used to calculate reliability for 2 to 5 raters. A total of 322 participants (202 female participants [62.7%]; 83 aged 40-49 years [25.8%]) rated the survey items (on a 7-point scale). All 11 items were rated as easy to understand (with a mean [SD] ranging from 5.2 [1.38] for the alignment of values item to 6.3 [0.87] for the evidence item) and easy to apply (with a mean [SD] ranging from 4.8 [1.49] for the alignment of values item to 6.1 [1.07] for the evidence item). Participants provided favorable feedback on the tool's instructions, which were considered clear (mean [SD], 5.8 [1.06]), helpful (mean [SD], 5.9 [1.00]), and complete (mean [SD], 5.8 [1.11]). Participants considered the tool easy to use (mean [SD], 5.4 [1.32]) and thought that it added value to the guideline enterprise (mean [SD], 5.9 [1.13]). Internal consistency of the items was high (Cronbach = 0.94). Positive correlations were found between the overall AGREE-REX score and the implementability score (r = 0.81) and the clinical credibility score (r = 0.76). This cross-sectional study found that the AGREE-REX tool can be useful in evaluating CPG recommendations, differentiating among them, and identifying those that are clinically credible and implementable for practicing health professionals and decision makers who use recommendations to inform clinical policy.

Controlling Viral Immuno-Inflammatory Lesions by Modulating Aryl Hydrocarbon Receptor Signaling

Ocular herpes simplex virus infection can cause a blinding CD4+ T cell orchestrated immuno-inflammatory lesion in the cornea called Stromal Keratitis (SK). A key to controlling the severity of SK lesions is to suppress the activity of T cells that orchestrate lesions and enhance the representation of regulatory cells that inhibit effector cell function. In this report we show that a single administration of TCDD (2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin), a non-physiological ligand for the AhR receptor, was an effective means of reducing the severity of SK lesions. It acted by causing apoptosis of Foxp3- CD4+ T cells but had no effect on Foxp3+ CD4+ Tregs. TCDD also decreased the proliferation of Foxp3- CD4+ T cells. The consequence was an increase in the ratio of Tregs to T effectors which likely accounted for the reduced inflammatory responses. In addition, in vitro studies revealed that TCDD addition to anti-CD3/CD28 stimulated naïve CD4+ T cells caused a significant induction of Tregs, but inhibited the differentiation of Th1 and Th17 cells. Since a single TCDD administration given after the disease process had been initiated generated long lasting anti-inflammatory effects, the approach holds promise as a therapeutic means of controlling virus induced inflammatory lesions

Who Laughs at a Rape Joke? Illiberal Responsiveness in Rodrigo Duterte\u27s Philippines

When a presidential contender makes a joke about lusting over a dead Australian missionary, calls the Pope the son of a whore, and confesses to killing criminals during his tenure as city mayor, one could expect that this candidate would not go very far. But not in the year 2016. Dubbed as ‘the year of voting dangerously,’ the Philippines rode the tide of global discontent and gave landslide victory to the controversial Rodrigo Duterte. This chapter examines the discursive underpinnings of Duterte’s rise to power by focusing on the process in which his supporters made ethical calculations from listening to his official speeches, live performance on television debates, and broader discussions in news and social media during the campaign period. We argue that Duterte’s ‘crass politics’ is a push back to the dominant moral politics perpetuated by institutions associated to the Philippines\u27 liberal democratic elite. While we condemn the Duterte regime’s disregard for human rights and due process, especially in the context of his bloody war on drugs, we also advocate a closer look at the ethics of Duterte’s responsiveness to deep-seated injuries endured by his constituencies both among marginalised and middle-class communities. Through a careful yet critical unpacking of his ‘crass politics of responsiveness’ from ethnographic research with Duterte supporters and media analysis of Duterte’s public performances, we hope to put forward a precise understanding of the emerging moral politics that underpins this unorthodox regime

Activation of Aryl Hydrocarbon Receptor (AhR) Leads to Reciprocal Epigenetic Regulation of FoxP3 and IL-17 Expression and Amelioration of Experimental Colitis

Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+) Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis.Dextran sodium sulphate (DSS) administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+) T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight) was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP) and mesenteric lymph nodes (MLN), during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+) but not AhR (-/-) mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment.These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation

Immune cell counts and risks of respiratory infections among infants exposed pre- and postnatally to organochlorine compounds: a prospective study

<p>Abstract</p> <p>Background</p> <p>Early-life chemical exposure may influence immune system development, subsequently affecting child health. We investigated immunomodulatory potentials of polychlorinated biphenyls (PCBs) and <it>p,p'</it>-DDE in infants.</p> <p>Methods</p> <p>Prenatal exposure to PCBs and <it>p,p'</it>-DDE was estimated from maternal serum concentrations during pregnancy. Postnatal exposure was calculated from concentrations of the compounds in mother's milk, total number of nursing days, and percentage of full nursing each week during the 3 month nursing period. Number and types of infections among infants were registered by the mothers (N = 190). White blood cell counts (N = 86) and lymphocyte subsets (N = 52) were analyzed in a subgroup of infants at 3 months of age.</p> <p>Results</p> <p>Infants with the highest prenatal exposure to PCB congeners CB-28, CB-52 and CB-101 had an increased risk of respiratory infection during the study period. In contrast, the infection odds ratios (ORs) were highest among infants with the lowest prenatal mono-<it>ortho </it>PCB (CB-105, CB-118, CB-156, CB-167) and di-<it>ortho </it>PCB (CB-138, CB-153, CB-180) exposure, and postnatal mono- and di-<it>ortho </it>PCB, and <it>p,p'</it>-DDE exposure. Similar results were found for pre- and postnatal CB-153 exposure, a good marker for total PCB exposure. Altogether, a negative relationship was indicated between infections and total organochlorine compound exposure during the whole pre- and postnatal period. Prenatal exposure to CB-28, CB-52 and CB-101 was positively associated with numbers of lymphocytes and monocytes in infants 3 months after delivery. Prenatal exposure to <it>p,p'</it>-DDE was negatively associated with the percentage of eosinophils. No significant associations were found between PCB and <it>p,p'</it>-DDE exposure and numbers/percentages of lymphocyte subsets, after adjustment for potential confounders.</p> <p>Conclusion</p> <p>This hypothesis generating study suggests that background exposure to PCBs and <it>p,p'</it>-DDE early in life modulate immune system development. Strong correlations between mono- and di-<it>ortho </it>PCBs, and <it>p,p'</it>-DDE exposures make it difficult to identify the most important contributor to the suggested immunomodulation, and to separate effects due to pre- and postnatal exposure. The suggested PCB and <it>p,p'</it>-DDE modulation of infection risks may have consequences for the health development during childhood, since respiratory infections early in life may be risk factors for asthma and middle ear infections.</p