Transgendering Viewers of Television

In response to the growing number of transgender characters on television, I explored how witnessing transgender representation on television is associated with an increase in viewers’ knowledge about the trans community, their empathy and understanding for the trans community, and their likelihood to advocate for the trans community. I hypothesized that witnessing trans representation on television is associated with greater understanding and empathy for the trans community, knowledge about trans experiences, and motivation to advocate for the trans community. The trans community specifically is becoming more visible thanks to television shows like Fox’s Pose. Gender and gender identity frameworks are nuanced but necessary for understanding and discussing the implications for representation of transgender people. In my research, I investigated in a multi-part survey questionnaire with 64 participants, completing various extents of it. The survey explored how viewing media with transgender representation was associated with participants’ self-reported takeaways from watching. From the responses, I gained insight as to how watching this representation was associated with participants’ responses to questions, which I designed to investigate the variables of interest to my hypothesis. I found there was significant positive associations between viewers’ amounts of trans representation watched overall and their reported greater levels of education and understanding about the trans community from watching. These greater levels of education and understanding from watching were significantly, positively associated with greater levels of willingness to advocate for the trans community and act in support of it with pronoun usage from watching. The results of this study have reaching implications about the associations between watching transgender representation on television viewer takeaways and greater levels of understanding for this community. From this we can understand how the increase in transgender representation in television may impact and continue to impact audience members

DOP28 Understanding the molecular mechanisms of anti-TNF treatment failure in patients with Crohn’s disease: A pilot serum proteomic analysis of the PANTS cohort

Background Proteomic biomarkers have been linked to anti-TNF treatment failure, but previous studies have been insufficiently powered to stratify associations by drug level. The Personalised Anti-TNF Therapy in Crohn’s disease (PANTS) is a prospective UK-wide study investigating treatment failure in 1610 anti-TNF naïve patients. We aimed to identify proteomic markers of treatment failure. Methods We sampled patients with primary non-response (PNR) (n = 223) and remission (n = 219) who had a baseline CRP ≥4 mg/l and/or calprotectin >100 µg/g. PNR was defined at week 14 as ongoing steroids, or both of HBI failed to fall by ≥3 points or to ≤4 and CRP failed to fall by ≥50% or to ≤3 mg/l. Non-remission at week 54 was defined as HBI >4 and CRP >3 mg/l and no steroids. Targeted serum proteomic analysis of 180 proteins using Olink Inflammation and Immune Response panels were performed. Mann–Whitney U tests were used to identify baseline proteins that predicted PNR and non-remission. Sub-group analyses stratified by drug level were undertaken. Pharmacokinetic (PK) failure was defined as PNR with low drug level (infliximab level <2 mg/l, adalimumab level <6 mg/l) and pharmacodynamic (PD) failure as PNR despite adequate drug level. Significant proteins were entered into multivariable logistic regression models and Bayesian information criterion (BIC) with backward stepwise selection were used to build predictive models of treatment failure. We applied 10-fold cross-validation to test the models. P-values of < 0.05 were considered significant. Results Elevated fibroblast growth factor 21 (FGF21) (OR 1.3, CI 1.1–1.4, p = 3.4 × 10–5) and interleukin-10 receptor subunit α (IL10RA) (OR 1.6, CI 1.2–2.1, p = 6.3 × 10–4) predicted PNR (Figure 1). At week 14, FGF21 (OR 1.5, CI 1.3–1.9, p = 1.8 × 10–6) and IL10RA (OR 1.8, CI 1.3–2.3, p = 5.8 × 10–5) levels were also associated with PNR. graphic Sub-group analyses showed baseline FGF21 (OR 1.4, CI 1.2–1.7, p = 2.0 × 10–4) predicted PK failure and that IL10-RA (OR 1.6, CI 1.1–2.2, p = 6.7 × 10–3) predicted PD failure (Figure 2). graphic In separate models, non-remission at week 54 was predicted by baseline (FGF21; OR 1.3, CI 1.1–1.4, p = 1.4 × 10–4, IL10-RA; OR 1.5, CI 1.1–2.0, p = 3.6 × 10–3) and week 14 (FGF21; OR 1.4, CI 1.2–1.7, p = 3.6 × 10–4, IL10-RA; OR 1.7, CI 1.3–2.4, p = 1.7 × 10–4) FGF21 and IL10-RA levels. Model validation of baseline FGF21 and IL10-RA showed an area under the curve of 0.61 (CI 0.57–0.64) for PNR and 0.60 (CI 0.56–0.64) for non-remission at week 54. Conclusion Our study identified FGF-21 and IL10-RA as proteins of interest associated with PK and PD treatment failure, respectively. Functional studies to determine the molecular mechanism driving dysregulation of these proteins are required.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

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-

How does virtual simulation impact on nursing students’ knowledge and self-efficacy for recognising and responding to deteriorating patients? A mixed methods study.

Background: Preparing undergraduate nursing students effectively for safe clinical practice continues to present significant challenges due to the impact of the Covid-19 pandemic, global nursing shortages, greater competition for quality clinical placements, and no guarantee that nursing students will have exposure to a deteriorating patient during their clinical placements. This is a concern because early warning signs of clinical deterioration are often not detected by nurses in a timely manner, and recognition and response to deteriorating patients is recognised globally as a major safety challenge (Haddeland et al., 2018). Aim: To explore the impact of using interactive virtual simulation case studies with facilitated debriefing (Eppich and Cheng, 2015) on nursing students’ knowledge and self-efficacy for recognising and responding to early signs of clinical deterioration in patients. Design & Methods: Mixed methods study with quasi-experimental pre/post design and focus groups. A convenience sample (n=88) final year undergraduate nursing students with half the sample at each sites randomly allocated to a treatment or control group. The treatment group received a virtual simulation intervention, debriefing, and participated in a focus group. Results: The treatment group had statistically significant higher levels of clinical self-efficacy from pre to post survey scores (65.34 and 80.12) compared to the control group (62.59 and 70.73) and significantly increased levels of knowledge in recognizing and responding to the deteriorating patient scores from pre to post survey (11.30 to 13.1) in comparison to the control group (10.33 and 9.92). Conclusions: study findings demonstrated the positive impact of a the virtual simulation intervention on knowledge and confidence of undergraduate nursing students from geographically diverse areas

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

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

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

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study.

BACKGROUND: We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. METHODS: Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. FINDINGS: Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1-46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7-43·7), 34·4% (29·9-39·0), and 34·7% (29·8-39·5), and for adalimumab 35·9% (95% CI 31·2-40·5), 32·9% (26·8-39·2), and 28·9% (21·9-36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1-10·0 mg/L for infliximab and 10·1-12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4-38·2), 54·5% (49·4-59·0), and 60·0% (54·1-65·2), and for adalimumab 32·1% (26·7-37·1), 47·2% (40·2-53·4), and 68·4% (50·9-79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30-0·67], adalimumab: 0·39 [0·22-0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11-1·95]), obesity (vs not obese 1·62 [1·08-2·42]), baseline white cell count (1·06 [1·02-1·11) per 1 × 109 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17-3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1-49·4) among patients treated with infliximab and 20·3% (13·8-26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31-0·52], adalimumab 0·42 [95% CI 0·24-0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13-1·88]) but not for adalimumab (HR 1·60 [0·92-2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20-3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11-2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. INTERPRETATION: Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs. FUNDING: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare