Modeling Policy and Agricultural Decisions in Afghanistan

Afghanistan is responsible for the majority of the world's supply of poppy crops, which are often used to produce illegal narcotics like heroin. This paper presents an agent-based model that simulates policy scenarios to characterize how the production of poppy can be dampened and replaced with licit crops over time. The model is initialized with spatial data, including transportation network and satellite-derived land use data. Parameters representing national subsidies, insurgent influence, and trafficking blockades are varied to represent different conditions that might encourage or discourage poppy agriculture. Our model shows that boundary-level interventions, such as targeted trafficking blockades at border locations, are critical in reducing the attractiveness of growing this illicit crop. The principle of least effort implies that interventions decrease to a minimal non-regressive point, leading to the prediction that increases in insurgency or other changes are likely to lead to worsening conditions, and improvements require substantial jumps in intervention resources.Comment: 16 pages, 5 figures; GeoJournal, 2012, 10.1007/s10708-012-9453-

Trading spaces: Afghan borderland brokers and the transformation of the margins

This chapter focuses on brokers and brokerage in the context of cross border smuggling or illicit trade. Drawing on illustrative case study material from the borderscapes of eastern and western Afghanistan, we shine a light on the lives of two brokers who act as go-betweens and gatekeepers in these complex and often conflictual transnational trading networks. One is a tribal broker in Nangarhar province on the Pakistan border, and another is an illicit trader in Nimroz province on the Iranian border. By focusing on their lives we aim to achieve two things: firstly, to present new empirical evidence on brokers, so as to better understand their lives, motivations, roles and effects – and in particular, how they adapted to border hardening and closures. Specifically, we explore the positionality of brokers in terms of their personal backgrounds, their ability to straddle lifeworlds, the ‘deal spaces’ they occupy, the resources and commodities they move, and the key pathways, corridors and choke points that channel and direct trade flows. We also examine the dynamics of brokerage, including the ways that brokers find solutions or ‘fixes’ to problems but rarely resolve them, and how brokers adapt to (or fail to adapt to) moments of rupture in fluid trading environments. Finally, we reveal the effects of brokerage in terms of how brokers cumulatively shape the ways in which states and markets function in marginal frontier and borderland environments. Though their agency is circumscribed, brokers are not merely mediators; they play a role in transforming and reconfiguring connections and relationships within political and market systems

OP21 Positivity thresholds of total infliximab and adalimumab anti-drug antibody assay: The prevalence of clearing and transient anti-drug antibodies in a national therapeutic drug monitoring service

Background Anti-drug antibodies can affect biopharmaceutical pharmacokinetics by increasing or decreasing drug clearance. Drug-tolerant (total), unlike drug-sensitive (free), antibody assays permit antibodies to be measured in the presence of a drug. We sought to confirm the positivity threshold of our total anti-tumour necrosis factor (TNF) antibody ELISA assays in a sample of healthy volunteers and to use this threshold to report the prevalence of clearing and transient antibodies in patients treated with infliximab and adalimumab. Methods Serum was obtained from a random sample of 498 anti-TNF-naïve healthy adults recruited to the Exeter Ten Thousand study and tested for total anti-drug antibodies to infliximab and adalimumab. Using recommendations for confirmatory anti-drug antibody validation, we used bootstrapping to calculate the 80% one-sided lower confidence interval [CI] of the 99th centile to define assay thresholds. We used paired drug and anti-drug antibody levels derived from our national therapeutic drug monitoring service to report the distribution of clearing (antibody positive, drug negative) vs. non-clearing (antibody positive, drug positive) antibodies. In patients with at least two test results, antibodies were classified as transient (single positive test with subsequent negative test) or persistent (at least two positive tests). Results The 80% one-sided lower CI of the 99th centile titre for total anti-drug antibody to infliximab and adalimumab were 8.7 AU/ml and 5.9 AU/ml, respectively. Using the manufacturer’s recommended threshold of 10 AU/ml for both total anti-TNF antibody assays, in healthy individuals, the prevalence of positive antibodies to infliximab and adalimumab was 1% (5/498) and 0.2% (1/498), respectively. Using the manufacturer’s threshold, at the time of last testing, of 7447 and 4054 patients treated with infliximab and adalimumab; 20.9% (n = 1,554) and 8.0% (n = 326) had clearing antibodies and 26.5% (n = 1973) and 12.1% (n = 490) had non-clearing antibodies, respectively (Figure 1). Using our newly defined threshold in the same cohorts; 21.1% (n = 1573) and 8.4% (n = 339) had clearing antibodies and 28.0% (n = 2083) and 20.0% (n = 812) had non-clearing antibodies, to infliximab and adalimumab, respectively. Amongst patients with at least two tests, most developed persistent antibodies (Figure 2). Irrespective of anti-TNF drug, or threshold used, less than 10% patients developed transient antibodies. graphic graphic Conclusion We report lower positivity thresholds for the IDKmonitor® total anti-TNF antibody ELISA assays than the manufacturer, in particular, for adalimumab. Transient antibody formation is uncommon: most patients develop persistent anti-drug antibodies that lead to drug clearance.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo), submitted versio

Census politics in deeply divided societies

Population censuses in societies that are deeply divided along ethnic, religious or linguistic lines can be sensitive affairs – particularly where political settlements seek to maintain peace through the proportional sharing of power between groups. This brief sets out some key findings from a research project investigating the relationship between census politics and the design of political institutions in Bosnia and Herzegovina, Kenya, Lebanon and Northern Ireland

Actually existing Silk Roads

This article explores the relevance of the concept of Silk Road for understandings patterns of trade and exchange between China, Eurasia and the Middle East. It is based on ethnographic fieldwork in the city of Yiwu, in China’s Zhejiang Province. Yiwu is a node in the global distribution of Chinese ‘small commodities’ and home to merchants and traders from across Asia and beyond. The article explores the role played by traders from Afghanistan in connecting the city of Yiwu to markets and trading posts in the world beyond. It seeks to bring attention to the diverse types of networks involved in such forms of trade, as well as their emergence and development over the past thirty years

Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian-randomization study

Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD. Methods: We used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). We tested observational and MR-based associations between GORD and four adiposity measures [body mass index (BMI), waist-hip ratio (WHR), a metabolically favourable higher body-fat percentage and waist circumference], smoking status, smoking frequency and caffeine consumption. Results: Observationally, all adiposity measures were associated with higher odds of GORD. Ever and current smoking were associated with higher odds of GORD. Coffee consumption was associated with lower odds of GORD but, among coffee drinkers, more caffeinated-coffee consumption was associated with higher odds of GORD. Using MR, we provide strong evidence that higher WHR and higher WHR adjusted for BMI lead to GORD. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded. This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference. Conclusions: These results provide strong evidence that a higher waist-hip ratio leads to GORD. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.S.E.J. is funded by the Medical Research Council (grant: MR/M005070/1). A.R.W., T.M.F and H.Y. are supported by the European Research Council grants: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC and 323195. H.Y. is also funded by the Diabetes UK RD Lawrence fellowship (grant: 17/0005594). R.N.B. is funded by the Wellcome Trust and Royal Society, grant 104150/Z/14/Z. J.T. is supported by an Academy of Medical Sciences (AMS) Springboard award, which is supported by the AMS, the Wellcome Trust, GCRF, the Government Department of Business, Energy and Industrial strategy, the British Heart Foundation and Diabetes UK (SBF004\1079). N.A.K. declares personal fees from Falk, Takeda and Pharmacosmos; other fees from Janssen; and non-financial support from Janssen, AbbVie and Celltrion outside the submitted work. J.R.G. received honoraria from Falk, AbbVie and Shield therapeutics, outside the submitted work for unrelated topics. T.A. reports grants from AbbVie, MSD, Napp Pharmaceuticals, Celltrion, Pfizer, Janssen and Celgene during this study; personal fees and non-financial support from Immunodiagnostik; personal fees and non-financial support from Napp Pharmaceuticals, AbbVie and MSD; personal fees from Celltrion and Pfizer; grants and personal fees from Takeda; and grants and non-financial support from Tillotts, outside the submitted work.published version, accepted version (12 month embargo), submitted versio

International federation of genomic medicine databases using GA4GH standards

We promote a shared vision and guide for how and when to federate genomic and health-related data sharing, enabling connections and insights across independent, secure databases. The GA4GH encourages a federated approach wherein data providers have the mandate and resources to share, but where data cannot move for legal or technical reasons. We recommend a federated approach to connect national genomics initiatives into a global network and precision medicine resource

Validating the positivity thresholds of drug-tolerant anti-infliximab and anti-adalimumab antibody assays

Background: When used proactively, drug-tolerant anti-tumour necrosis factor (TNF) antibody assays provide early opportunity to suppress immunogenicity. Aim: To validate positivity thresholds of IDKmonitor drug-tolerant anti-infliximab and -adalimumab antibody assays. Methods: We applied positivity thresholds, defined by testing sera from 498 anti-TNF naive healthy adults, from the Exeter Ten Thousand study to data from our therapeutic drug monitoring (TDM) service and Personalised Anti-TNF Therapy in Crohn's disease (PANTS) cohort to explore associations with drug level and treatment outcomes. Results: The 80% one-sided lower confidence interval of the 99th centile concentration for anti-infliximab and -adalimumab antibodies were lower than the manufacturers threshold of 10 arbitrary units (AU)/mL; 9 and 6 AU/mL, respectively. Using these new thresholds in the TDM cohort, more adalimumab- than infliximab- (11.2% [814/7272] vs 3.1% [390/12 683] P < 0.0001) treated patients were reclassified as antibody-positive. Adalimumab drug concentrations in this reclassified group (median 8.1, interquartile range [IQR] 5.5-11.0 mg/L) were lower than those below the new threshold (<5AU/mL) (median 9.9, IQR 7.1-13.0 mg/L; P < 0.0001), but higher than at the manufacturer's threshold (10-29 AU/mL) (median 5.9 mg/L, IQR 3.5-8.7; P < 0.0001). No difference in infliximab drug concentration was observed using the new or manufacturer's positivity threshold (P = 0.11). In the PANTS cohort, patients with anti-adalimumab antibody concentrations at or above the new threshold were more likely to be in primary non-response (25/68 [37%] vs. 64/332 [19%], P = 0.0035), and non-remission at week 54 (51/62 [82%] vs. 168/279 [60%], P = 0.0011), than patients with anti-drug antibody concentrations in the group below the new threshold (0-5 AU/mL); this was not seen for anti-infliximab antibodies. Conclusion: Laboratories should derive antibody positivity thresholds for assays they use. For adalimumab, low-concentration anti-drug antibodies were associated with lower drug levels and treatment failure.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo), submitted versio

A qualitative exploration of mental health professionals' experience of working with survivors of trauma in Sri Lanka

This study explored the struggles and rewards of trauma work and the notion that individuals are changed in some way by the work they do with survivors of traumatic events. Interpretative phenomenological analysis of interviews with twelve mental health professionals working in Sri Lanka has shown these changes to have both an accumulated negative emotional impact but also to simultaneously contain positive, growth-promoting and personally satisfying aspects. There is a bias prevalent in the trauma literature towards focusing on the many negative aspects of the impact of working with survivors of trauma or surveying the moderating factors for managing secondary trauma. The present research, instead, uses the paradigm of adversarial growth to demonstrate that when mental health professionals rebuild their assumptive world in light of their experiences of working with survivors of trauma there are valuable opportunities for personal, and by implication, professional growth. This study is of a qualitative nature and explores phenomenologically grounded knowledge seeking to gain an understanding of the lived experiences reported by mental health professionals working with survivors of trauma, and the subjective and collective meanings that shape these experiences