Occupational risks, health needs and victim identification of trafficked fishermen in the Greater Mekong Subregion (GMS)

Background: Commercial fishing at sea is among the world’s most dangerous occupations. With 24- hour cycles of physically demanding work, adequate rest and recovery are often elusive in deep-sea commercial fishing. Human trafficking in the fishing industry has been identified as a problem in the Greater Mekong Subregion (GMS), with reports documenting 18-24 hour work days and severe violence. As a largely unregulated sector with activities conducted in international waters far from shore and outside of national jurisdiction, the commercial fishing industry poses unique risks to workers health, safety and well-being. Yet, research on the health needs of trafficked fishermen is sparse. Moreover, extraordinarily little research exists on policy responses to this problem. This thesis aims to investigate the health needs of trafficked fishermen, and understand how victim identification and assistance are being conducted in Thailand, a key transit and destination country for fishing trafficking. Methods: The thesis comprises four studies: i) a systematic review of the literature on occupational health among GMS migrant and trafficked fishermen and other seafarers; ii) a quantitative exploration of factors associated with work-related injuries and violence among labour-trafficked men that used post-trafficking services in the GMS; iii) a mixed methods study examining the health needs of trafficked fishermen and health service provision; and iv) a qualitative study examining how potentially trafficked fishermen are identified and assisted by frontline responders to trafficking in Thailand. Results: The systematic review found limited research on occupational hazards faced by migrant and trafficked fishermen and seafarers. Findings from quantitative analysis of a cohort of labour-trafficked males from different sectors indicated that work-related injuries were associated with severe violence and being trafficked for fishing. Ever having experienced violence was associated with being in the fishing sector and fluency in the language of the destination country. Having documents did not appear to be protective against injuries or violence. The mixed methods study found that dizzy spells and exhaustion were common among trafficked fishermen. There were strong associations between physical health symptoms and severe violence, injuries, or detention by immigration authorities. Trafficked fishermen are perceived by boat captains to be disposable when injured or sick. While health can be a means to reach trafficked men, health and welfare providers faced challenges including language barriers and negotiating payment for services for uninsured fishermen and accident compensation with employers. The qualitative study found that frontline responders perceived trafficking to take place outside of Thai waters and that migrant brokers caused employers to inadvertently traffick men. Confusion about whether debt bondage or withholding of documents counted as trafficking indicators may be linked to ambiguous inclusion of these indicators in policy documents. Institutional constraints included limited staff with increased remits and interpreter shortages. Conclusion: There is evidence that trafficked fishermen face more extreme occupational hazards and abuse compared to men trafficked into other sectors, with a high burden of physical and mental ill-health experienced. Promising strategies employed by health and welfare providers to reach men highlight the importance of targeted outreach. Beliefs about the locus of the problem and institutional constraints among frontline responders indicate that further training on trafficking indicators, as well as institutional change, is needed to improve victim identification and assistance

Challenges to pre-migration interventions to prevent human trafficking: Results from a before-and-after learning assessment of training for prospective female migrants in Odisha, India

Background: Awareness-raising and pre-migration training are popular strategies to prevent human trafficking. Programmatic theories assume that when prospective migrants are equipped with information about risks, they will make more-informed choices, ultimately resulting in safe migration. In 2016, India was estimated to have 8 million people in modern slavery, including those who migrate internally for work. Work in Freedom (WiF) was a community-based trafficking prevention intervention. This study evaluated WiF’s pre-migration knowledge-building activities for female migrants in Odisha to prevent future labour-related exploitation. / Methods: Pre- and post- training questionnaires were administered to women (N = 347) who participated in a two-day pre-migration training session. Descriptive analysis and unadjusted analyses (paired t-tests, McNemar’s tests, Wilcoxon signed ranks tests) examined differences in women’s knowledge scores before and after training. Adjusted analyses used mixed effects models to explore whether receiving information on workers’ rights or working away from home prior to the training was associated with changes in scores. Additionally, we used data from a household survey (N = 4,671) and survey of female migrants (N = 112) from a population sample in the same district to evaluate the intervention’s rationale and implementation strategy. / Results: Female participants were on average 37.3 years-old (SD 11) and most (67.9%) had no formal education. Only 11 participants (3.2%) had previous migration experience. Most participants (90.5%) had previously received information or advice on workers’ rights or working away from home. Compared to female migrants in the population, training participants were different in age, caste and religion. Awareness about migration risks, rights and collective bargaining was very low initially and remained low post-training, e.g. of 13 possible migration risks, before the training, participants named an average of 1.2 risks, which increased only slightly to 2.1 risks after the training (T(346) = -11.64, p<0.001). Changes were modest for attitudes about safe and risky migration practices, earnings and savings. Before the training, only 34 women (10.4%) considered migrating, which reduced to 25 women (7.7%) post-training (X2 = 1.88, p = 0.169)—consistent with the low prevalence (7% of households) of female migration locally. Women’s attitudes remained relatively fixed about the shame associated with paid domestic work. Survey data indicated focusing on domestic work did not correspond to regional migration trends, where women migrate primarily for construction or agriculture work. / Conclusion: The apparent low effectiveness of the WiF short-duration migration training may be linked to the assumption that individual changes in knowledge will lead to shifts in social norms. The narrow focus on such individual-level interventions may overestimate an individual’s agency. Findings indicate the importance of intervention development research to ensure activities are conducted in the right locations, target the right populations, and have relevant content. Absent intervention development research, this intervention suffered from operating in a site that had very few migrant women and a very small proportion migrating for domestic work—the focus of the training. To promote better development investments, interventions should be informed by local evidence and subjected to rigorous theory-based evaluation to ensure interventions achieve the most robust design to foster safe labour migration for women

Amyloid precursor protein processing in human neurons with an allelic series of the PSEN1 intron 4 deletion mutation and total presenilin-1 knockout

Mutations in presenilin-1 (PSEN1), encoding the catalytic subunit of the amyloid precursor protein-processing enzyme γ-secretase, cause familial Alzheimer’s disease. However, the mechanism of disease is yet to be fully understood and it remains contentious whether mutations exert their effects predominantly through gain or loss of function. To address this question, we generated an isogenic allelic series for the PSEN1 mutation intron 4 deletion; represented by control, heterozygous and homozygous mutant induced pluripotent stem cells in addition to a presenilin-1 knockout line. Induced pluripotent stem cell-derived cortical neurons reveal reduced, yet detectable amyloid-beta levels in the presenilin-1 knockout line, and a mutant gene dosage-dependent defect in amyloid precursor protein processing in PSEN1 intron 4 deletion lines, consistent with reduced processivity of γ-secretase. The different effects of presenilin-1 knockout and the PSEN1 intron 4 deletion mutation on amyloid precursor protein-C99 fragment accumulation, nicastrin maturation and amyloid-beta peptide generation support distinct consequences of familial Alzheimer’s disease-associated mutations and knockout of presenilin-1 on the function of γ-secretase

P2Y12 platelet inhibition in clinical practice

Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines

Pre-referral rectal artesunate in severe malaria: flawed trial

<p>Abstract</p> <p>Background</p> <p>Immediate injectable treatment is essential for severe malaria. Otherwise, the afflicted risk lifelong impairment or death. In rural areas of Africa and Asia, appropriate care is often miles away. In 2009, Melba Gomes and her colleagues published the findings of a randomized, placebo-controlled trial of rectal artesunate for suspected severe malaria in such remote areas. Enrolling nearly 18,000 cases, the aim was to evaluate whether, as patients were in transit to a health facility, a pre-referral artesunate suppository blocked disease progression sufficiently to reduce these risks. The affirmative findings of this, the only trial on the issue thus far, have led the WHO to endorse rectal artesunate as a pre-referral treatment for severe malaria. In the light of its public health importance and because its scientific quality has not been assessed for a systematic review, our paper provides a detailed evaluation of the design, conduct, analysis, reporting, and practical features of this trial.</p> <p>Results</p> <p>We performed a checklist-based and an in-depth evaluation of the trial. The evaluation criteria were based on the CONSORT statement for reporting clinical trials, the clinical trial methodology literature, and practice in malaria research. Our main findings are: The inclusion and exclusion criteria and the sample size justification are not stated. Many clearly ineligible subjects were enrolled. The training of the recruiters does not appear to have been satisfactory. There was excessive between center heterogeneity in design and conduct. Outcome evaluation schedule was not defined, and in practice, became too wide. Large gaps in the collection of key data were evident. Primary endpoints were inconsistently utilized and reported; an overall analysis of the outcomes was not done; analyses of time to event data had major flaws; the stated intent-to-treat analysis excluded a third of the randomized subjects; the design-indicated stratified or multi-variate analysis was not done; many improper subgroups were analyzed in a post-hoc fashion; the analysis and reporting metric was deficient. There are concerns relating to patient welfare at some centers. Exclusion of many cases from data analysis compromised external validity. A bias-controlled reanalysis of available data does not lend support to the conclusions drawn by the authors.</p> <p>Conclusions</p> <p>This trial has numerous serious deficiencies in design, implementation, and methods of data analysis. Interpretation and manner of reporting are wanting, and the applicability of the findings is unclear. The trial conduct could have been improved to better protect patient welfare. The totality of these problems make it a flawed study whose conclusions remain subject to appreciable doubt.</p

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Globalization and Health: developing the journal to advance the field

Founded in 2005, Globalization and Health was the first open access global health journal. The journal has since expanded the field, and its influence, with the number of downloaded papers rising 17-fold, to over 4 million. Its ground-breaking papers, leading authors -including a Nobel Prize winner- and an impact factor of 2.25 place it among the top global health journals in the world. To mark the ten years since the journal’s founding, we, members of the current editorial board, undertook a review of the journal’s progress over the last decade. Through the application of an inductive thematic analysis, we systematically identified themes of research published in the journal from 2005 to 2014. We identify key areas the journal has promoted and consider these in the context of an existing framework, identify current gaps in global health research and highlight areas we, as a journal, would like to see strengthened