Global governance approaches to addressing illegal logging: Uptake and lessons learned

One of the most challenging tasks facing development agencies, trade ministries, environmental groups, social activists and forest-focused business interests seeking to ameliorate illegal logging and related timber trade is to identify and nurture promising global governance interventions capable of helping improve compliance to governmental policies and laws at national, subnational and local levels. This question is especially acute for developing countries constrained by capacity challenges and “weak states” (Risse, 2011). This chapter seeks to shed light on this task by asking four related questions: How do we understand the emergence of illegal logging as a matter of global interest? What are the types of global interventions designed to improve domestic legal compliance? How have individual states responded to these global efforts? What are the prospects for future impacts and evolution? We proceed in the following steps. Following this introduction, step two reviews how the problem of “illegal logging” emerged on the international agenda. Step three reviews leading policy interventions that resulted from this policy framing. Step four reviews developments in selected countries/regions around the world according to their place on the global forest products supply chain: consumers (United States, Europe and Australia); middle of supply chain manufacturers (China and South Korea) and producers (Russia; Indonesia; Brazil and Peru; Ghana, Cameroon and the Republic of Congo). We conclude by reflecting on key trends that emerge from this review relevant for understanding the conditions through which legality might make a difference in addressing critical challenges

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Does a complex intervention targeting communities, health facilities and district health managers increase the utilisation of community-based child health services? A before and after study in intervention and comparison areas of Ethiopia.

INTRODUCTION: Ethiopia successfully reduced mortality in children below 5 years of age during the past few decades, but the utilisation of child health services was still low. Optimising the Health Extension Programme was a 2-year intervention in 26 districts, focusing on community engagement, capacity strengthening of primary care workers and reinforcement of district accountability of child health services. We report the intervention's effectiveness on care utilisation for common childhood illnesses. METHODS: We included a representative sample of 5773 households with 2874 under-five children at baseline (December 2016 to February 2017) and 10 788 households and 5639 under-five children at endline surveys (December 2018 to February 2019) in intervention and comparison areas. Health facilities were also included. We assessed the effect of the intervention using difference-in-differences analyses. RESULTS: There were 31 intervention activities; many were one-off and implemented late. In eight districts, activities were interrupted for 4 months. Care-seeking for any illness in the 2 weeks before the survey for children aged 2-59 months at baseline was 58% (95% CI 47 to 68) in intervention and 49% (95% CI 39 to 60) in comparison areas. At end-line it was 39% (95% CI 32 to 45) in intervention and 34% (95% CI 27 to 41) in comparison areas (difference-in-differences -4 percentage points, adjusted OR 0.49, 95% CI 0.12 to 1.95). The intervention neither had an effect on care-seeking among sick neonates, nor on household participation in community engagement forums, supportive supervision of primary care workers, nor on indicators of district accountability for child health services. CONCLUSION: We found no evidence to suggest that the intervention increased the utilisation of care for sick children. The lack of effect could partly be attributed to the short implementation period of a complex intervention and implementation interruption. Future funding schemes should take into consideration that complex interventions that include behaviour change may need an extended implementation period. TRIAL REGISTRATION NUMBER: ISRCTN12040912

Capacity of health facilities for diagnosis and treatment of HIV/AIDS in Ethiopia

Background: There are dearth of literature on the capacity of the health system to diagnose and treat HIV/AIDS in Ethiopia. In this study we evaluated the capacity of health facilities for HIV/AIDS care, its spatial distribution and variations by regions and zones in Ethiopia. Methods: We analyzed the Service Provision Assessment plus (SPA+) survey data that were collected in 2014 in all regions of Ethiopia. We assessed structural, process and overall capacity of the health system based on the Donabedian quality of care model. We included 5 structural and 8 process indicators and overall capacity score was constructed by taking the average of all indicators. Multiple linear regression was done using STATA 14 to assess the association of the location and types of health facilities with overall capacity score. Maps displaying the average capacity score at Zonal level were produced using ArcGIS Desktop v10.3 (Environmental Systems Research Institute Inc., Redlands CA, USA). Results: A total of 873 health facilities were included in the analysis. Less than 5% of the private facilities provided antiretroviral therapy (ART); had national ART guideline, baseline CD4 count or viral load and tuberculosis screening mechanisms. Nearly one-third of the health centers (34.9%) provided ART. Public hospitals have better capacity score (77.1%) than health centers (45.9%) and private health facilities (24.8%). The overall capacity score for urban facilities (57.1%) was higher than that of the rural (38.2%) health facilities (β = 15.4, 95% CI: 11.7, 19.2). Health centers (β = − 21.4, 95% CI: -25.4, − 17.4) and private health facilities (β = − 50.9, 95% CI: -54.8, − 47.1) had lower overall capacity score than hospitals. Facilities in Somali (β = − 13.8, 95% CI: -20.6, − 7.0) and SNNPR (β = − 5.0, 95% CI: -9.8, − 0.1) regions had lower overall capacity score than facilities in the Oromia region. Zones located in emerging regions such as Gambella and Benishangul Gumz and in remote areas of Oromia and SNNPR had lower capacity score in terms of process indicators. Conclusions: There is a significant geographical heterogeneity on the capacity of health facilities for HIV/AIDS care and treatment in Ethiopia. Targeted capacity improvement initiatives are recommended with focus on health centers and private health facilities, and emerging Regions and the rural and remote areas

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Onchocerciasis: The Pre-control Association between Prevalence of Palpable Nodules and Skin Microfilariae

*Background*: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of

Multiple evolutionary origins of Trypanosoma evansi in Kenya

Trypanosoma evansi is the parasite causing surra, a form of trypanosomiasis in camels and other livestock, and a serious economic burden in Kenya and many other parts of the world. Trypanosoma evansi transmission can be sustained mechanically by tabanid and Stomoxys biting flies, whereas the closely related African trypanosomes T. brucei brucei and T. b. rhodesiense require cyclical development in tsetse flies (genus Glossina) for transmission. In this study, we investigated the evolutionary origins of T. evansi. We used 15 polymorphic microsatellites to quantify levels and patterns of genetic diversity among 41 T. evansi isolates and 66 isolates of T. b. brucei (n = 51) and T. b. rhodesiense (n = 15), including many from Kenya, a region where T. evansi may have evolved from T. brucei. We found that T. evansi strains belong to at least two distinct T. brucei genetic units and contain genetic diversity that is similar to that in T. brucei strains. Results indicated that the 41 T. evansi isolates originated from multiple T. brucei strains from different genetic backgrounds, implying independent origins of T. evansi from T. brucei strains. This surprising finding further suggested that the acquisition of the ability of T. evansi to be transmitted mechanically, and thus the ability to escape the obligate link with the African tsetse fly vector, has occurred repeatedly. These findings, if confirmed, have epidemiological implications, as T. brucei strains from different genetic backgrounds can become either causative agents of a dangerous, cosmopolitan livestock disease or of a lethal human disease, like for T. b. rhodesiense

Electric Field Exposure Triggers and Guides Formation of Pseudopod-Like Blebs in U937 Monocytes

We describe a new phenomenon of anodotropic pseudopod-like blebbing in U937 cells stimulated by nanosecond pulsed electric field (nsPEF). In contrast to regular, round-shaped blebs, which are often seen in response to cell damage, pseudopod-like blebs (PLBs) formed as longitudinal membrane protrusions toward anode. PLB length could exceed the cell diameter in 2 min of exposure to 60-ns, 10-kV/cm pulses delivered at 10-20 Hz. Both PLBs and round-shaped nsPEF-induced blebs could be efficiently inhibited by partial isosmotic replacement of bath NaCl for a larger solute (sucrose), thereby pointing to the colloid-osmotic water uptake as the principal driving force for bleb formation. In contrast to round-shaped blebs, PLBs retracted within several minutes after exposure. Cells treated with 1 nM of the actin polymerization blocker cytochalasin D were unable to form PLBs and instead produced stationary, spherical blebs with no elongation or retraction capacity. Live cell fluorescent actin tagging showed that during elongation actin promptly entered the PLB interior, forming bleb cortex and scaffold, which was not seen in stationary blebs. Overall, PLB formation was governed by both passive (physicochemical) effects of membrane permeabilization and active cytoskeleton assembly in the living cell. To a certain extent, PLB mimics the membrane extension in the process of cell migration and can be employed as a nonchemical model for studies of cytomechanics, membrane-cytoskeleton interaction and cell motility

Molecular pathways involved in the synergistic interaction of the PKCβ inhibitor enzastaurin with the antifolate pemetrexed in non-small cell lung cancer cells

Conventional regimens have limited impact against non-small cell lung cancer (NSCLC). Current research is focusing on multiple pathways as potential targets, and this study investigated molecular mechanisms underlying the combination of the PKCβ inhibitor enzastaurin with the multitargeted antifolate pemetrexed in the NSCLC cells SW1573 and A549. Pharmacologic interaction was studied using the combination-index method, while cell cycle, apoptosis induction, VEGF secretion and ERK1/2 and Akt phosphorylation were studied by flow cytometry and ELISAs. Reverse transcription–PCR, western blot and activity assays were performed to assess whether enzastaurin influenced thymidylate synthase (TS) and the expression of multiple targets involved in cancer signaling and cell cycle distribution. Enzastaurin-pemetrexed combination was highly synergistic and significantly increased apoptosis. Enzastaurin reduced both phosphoCdc25C, resulting in G2/M checkpoint abrogation and apoptosis induction in pemetrexed-damaged cells, and GSK3β and Akt phosphorylation, which was additionally reduced by drug combination (−58% in A549). Enzastaurin also significantly reduced pemetrexed-induced upregulation of TS expression, possibly through E2F-1 reduction, whereas the combination decreased TS in situ activity (>50% in both cell lines) and VEGF secretion. The effects of enzastaurin on signaling pathways involved in cell cycle control, apoptosis and angiogenesis, as well as on the expression of genes involved in pemetrexed activity provide a strong experimental basis to their evaluation as pharmacodynamic markers in clinical trials of enzastaurin-pemetrexed combination in NSCLC patients

Nanoelectropulse-driven membrane perturbation and small molecule permeabilization

BACKGROUND: Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization. RESULTS: In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to unipolar pulses, which perturb membrane phospholipid order, tracked with FM1-43 fluorescence, only at the anode side of the cell, bipolar pulses redistribute phospholipids at both the anode and cathode poles, consistent with migration of the anionic PS head group in the transmembrane field. In addition, we demonstrate that, as predicted by the membrane charging hypothesis, a train of shorter pulses requires higher fields to produce phospholipid scrambling comparable to that produced by a time-equivalent train of longer pulses (for a given applied field, 30, 4 ns pulses produce a weaker response than 4, 30 ns pulses). Finally, we show that influx of YO-PRO-1, a fluorescent dye used to detect early apoptosis and activation of the purinergic P2X(7 )receptor channels, is observed after exposure of Jurkat T lymphoblasts to sufficiently large numbers of pulses, suggesting that membrane poration occurs even with nanosecond pulses when the electric field is high enough. Propidium iodide entry, a traditional indicator of electroporation, occurs with even higher pulse counts. CONCLUSION: Megavolt-per-meter electric pulses as short as 3 ns alter the structure of the plasma membrane and permeabilize the cell to small molecules. The dose responses of cells to unipolar and bipolar pulses ranging from 3 ns to 30 ns duration support the hypothesis that a field-driven charging of the membrane dielectric causes the formation of pores on a nanosecond time scale, and that the anionic phospholipid PS migrates electrophoretically along the wall of these pores to the external face of the membrane