Are Welsh primary schools Sunproofed? Results of a national survey Part 1: Scoping the landscape of sun safety policies in Wales.

BACKGROUND: Schools with formal sun safety polices generally show better sun safety practices than schools without. OBJECTIVES: Understand the extent to which Welsh primary schools have sun safety policies; identify key characteristics of policies; assess whether policy adoption varies by school characteristics; and consider what support schools need to develop sun safety policies. METHODS: An online multiple-choice survey distributed to all 1241 primary schools in Wales asking about sun safety. RESULTS: In total, 471/1241 (38.0%) schools responded. Of these, 183 (39.0%) reported having a formal sun safety policy. Welsh medium schools (p=0.036) and schools in North Wales (p=0.008) were more likely to report having a policy. Schools with a higher percentage of pupils receiving free school meals (p=0.046) and with lower attendance rates (p=0.008) were less likely to report having a sun safety policy.Primary reasons for schools not having a policy included: 'unaware of the need' (34.6%); needing assistance with policy development (30.3%) and 'not got around to it' (26.8%). CONCLUSION: With less than half of schools reporting a sun safety policy and variation in the presence/absence of a policy by school characteristics, our survey shows inconsistency in formal sun safety provision in Welsh schools. Findings also suggest that schools are unaware of the importance of sun safety and need support to develop and implement policies. This snapshot of the current situation in primary schools in Wales provides a basis upon which the comprehensiveness, effectiveness, and implementation of sun safety policies can be further evaluated.

Community-Wide Universal Human Immunodeficiency Virus (HIV) Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

Blurring cluster randomized trials and observational studies: Two-Stage TMLE for subsampling, missingness, and few independent units.

Cluster randomized trials (CRTs) often enroll large numbers of participants; yet due to resource constraints, only a subset of participants may be selected for outcome assessment, and those sampled may not be representative of all cluster members. Missing data also present a challenge: if sampled individuals with measured outcomes are dissimilar from those with missing outcomes, unadjusted estimates of arm-specific endpoints and the intervention effect may be biased. Further, CRTs often enroll and randomize few clusters, limiting statistical power and raising concerns about finite sample performance. Motivated by SEARCH-TB, a CRT aimed at reducing incident tuberculosis infection, we demonstrate interlocking methods to handle these challenges. First, we extend Two-Stage targeted minimum loss-based estimation to account for three sources of missingness: (i) subsampling; (ii) measurement of baseline status among those sampled; and (iii) measurement of final status among those in the incidence cohort (persons known to be at risk at baseline). Second, we critically evaluate the assumptions under which subunits of the cluster can be considered the conditionally independent unit, improving precision and statistical power but also causing the CRT to behave like an observational study. Our application to SEARCH-TB highlights the real-world impact of different assumptions on measurement and dependence; estimates relying on unrealistic assumptions suggested the intervention increased the incidence of TB infection by 18% (risk ratio [RR]=1.18, 95% confidence interval [CI]: 0.85-1.63), while estimates accounting for the sampling scheme, missingness, and within community dependence found the intervention decreased the incident TB by 27% (RR=0.73, 95% CI: 0.57-0.92).

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

OBJECTIVES: Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. METHODS: Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. RESULTS: Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study, and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. CONCLUSIONS: Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

A UK-wide study to describe resource consumption and waste management practices in skin surgery including Mohs micrographic surgery.

BACKGROUND: There is a lack of national guidance specifying how skin surgery, including Mohs micrographic surgery (MMS), should be conducted, leading to a degree of heterogeneity in the set-up of skin surgery services and how skin surgeries are performed. OBJECTIVES: To provide the first UK-wide cross-sectional study reporting real-world data on the set-up and waste management practices of skin surgery, including MMS. METHODS: A UK-wide service evaluation study was conducted between 1 March 2022 and 30 June 2022 using a standardized data collection pro forma. Twelve participating sites from England, Northern Ireland, Scotland and Wales provided data from 115 skin surgery lists involving 495 patients and 547 skin surgery procedures between 1 March 2022 and 30 June 2022. RESULTS: Mean total weight of nonsharps skin surgery waste was 0.52 kg per procedure (0.39 kg clinical waste, 0.05 kg general waste and 0.08 kg recycling waste). Data from a single site using disposable surgical instruments reported a mean of only 0.25 kg of sharps waste per procedure. The recycling rate ranged between 0% and 44% across the cohort with a mean recycling rate of 16%. CONCLUSIONS: We advocate that staff transition to the British Society of Dermatological Surgery 2022 sustainability guidance, which made wide-ranging recommendations to facilitate staff to transition to sustainable practices in skin surgery.

International, prospective cohort study comparing non-absorbable versus absorbable sutures for skin surgery: CANVAS service evaluation.

BACKGROUND: Absorbable or non-absorbable sutures can be used for superficial skin closure following excisional skin surgery. There is no consensus among clinicians nor high-quality evidence supporting the choice of suture. The aim of the present study was to determine current suture use and complications at 30 days after excisional skin surgery. METHODS: An international, prospective service evaluation of adults undergoing excision of skin lesions (benign and malignant) in primary and secondary care was conducted from 1 September 2020 to 15 April 2021. Routine patient data collected by UK and Australasian collaborator networks were uploaded to REDCap©. Choice of suture and risk of complications were modelled using multivariable logistic regression. RESULTS: Some 3494 patients (4066 excisions) were included; 3246 (92.9 per cent) were from the UK and Ireland. Most patients were men (1945, 55.7 per cent), Caucasian (2849, 81.5 per cent) and aged 75-84 years (965, 27.6 per cent). The most common clinical diagnosis was basal cell carcinoma (1712, 42.1 per cent). Dermatologists performed most procedures, with 1803 excisions (44.3 per cent) on 1657 patients (47.4 per cent). Most defects were closed primarily (2856, 81.9 per cent), and there was equipoise in regard to use of absorbable (2127, 57.7 per cent) or non-absorbable (1558, 42.2 per cent) sutures for superficial closure. The most common complications were surgical-site infection (103, 2.9 per cent) and delayed wound healing (77, 2.2 per cent). In multivariable analysis, use of absorbable suture type was associated with increased patient age, geographical location (UK and Ireland), and surgeon specialty (oral and maxillofacial surgery and plastic surgery), but not with complications. CONCLUSION: There was equipoise in suture use, and no association between suture type and complications. Definitive evidence from randomized trials is needed.

Enhancing Efficacy of TCR-engineered CD4 + T Cells Via Coexpression of CD8α.

Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase the depth and durability of clinical responses and broaden efficacy toward additional indications. In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector to coexpress an affinity-enhanced HLA class I-restricted TCR directed against MAGE-A4 alongside a CD8α coreceptor. We hypothesized that this approach would enhance CD4 + T-cell helper and effector functions, possibly leading to a more potent antitumor response. Activation of transduced CD4 + T cells was measured by detecting CD40 ligand expression on the surface and cytokine and chemokine secretion from CD4 + T cells and dendritic cells cultured with melanoma-associated antigen A4 + tumor cells. In addition, T-cell cytotoxic activity against 3-dimensional tumor spheroids was measured. Our data demonstrated that CD4 + T cells coexpressing the TCR and CD8α coreceptor displayed enhanced responses, including CD40 ligand expression, interferon-gamma secretion, and cytotoxic activity, along with improved dendritic cell activation. Therefore, our study supports the addition of the CD8α coreceptor to HLA class I-restricted TCR-engineered T cells to enhance CD4 + T-cell functions, which may potentially improve the depth and durability of antitumor responses in patients.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

OCCURRENCE OF MANGE IN AMERICAN BLACK BEARS (URSUS AMERICANUS) IN NEW YORK STATE, USA.

Mange, a parasitic skin disease caused by various species of mites, is found in free-ranging wildlife populations and has been increasingly reported in American black bears (Ursus americanus) over the last decade in New York State (NYS), USA. Our goal was to describe the geographic, seasonal, and demographic factors associated with mange in this species in NYS. Our retrospective study used historic, opportunistic data from diagnostic necropsy records and visual sighting reports collected by the NYS Wildlife Health Program from 2009 to 2018. We used chi-square tests for independence and odds ratios to examine whether geographic location, year, season, sex, age, and reason for laboratory submission were associated with mange in bears. We used maps and seasonal analysis to investigate emerging patterns. We confirmed increased black bear mange reports in recent years. Necropsy data revealed more bears submitted to the laboratory because of mange, mainly caused by Sarcoptes scabiei; females were more likely than males to present with sarcoptic mange. We found that cases of mange in the Northern Zone were widely disseminated throughout the region, whereas cases in the Southern Zone were concentrated in two areas along the Pennsylvania border. Seasonally, mange cases showed peaks occurring in late spring to early summer and in fall. Our results were on the basis of available data; a comprehensive statewide surveillance program would be useful to better understand the apparent increase in mange and its potential impact on both the welfare of individual animals and the population of black bears in NYS. Additional research on the timing of transmission dynamics associated with females in winter dens may be helpful to wildlife managers to identify strategies to mitigate deleterious spread of the disease in black bears.

Clinicopathological characteristics of individuals with coexisting melanoma and chronic lymphocytic leukaemia: a multicentre cohort study.

BACKGROUND: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL. AIMS: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL. METHODS: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland. RESULTS: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group. CONCLUSIONS: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL.

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 2: feasibility data from a multicentre prospective observational cohort study to inform a future randomized controlled trial.

BACKGROUND: Compression therapy is considered beneficial for postsurgical lower leg wound healing by secondary intention; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. AIM: To determine the feasibility of recruitment and estimate recruitment rate; to understand the standard postoperative wound management pathway; to determine uptake of optional additional clinic visits for healing confirmation; and to explore patient acceptability of compression bandaging and plan a future RCT. METHODS: Participant recruitment was performed from secondary care dermatology clinics, during a period of 22 months. Inclusion criteria were age ≥ 18 years, planned excision of keratinocyte cancer on the lower leg with healing by secondary intention and an ankle-brachial pressure index of ≥ 0.8. Exclusion criteria were planned primary closure/graft or flap; inability to receive, comply with or tolerate high compression; planned compression; or suspected melanoma. Patients were followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information was collected on healthcare resource use, unplanned compression, wound healing and an optional clinic visit to confirm healing. RESULTS: This study recruited 58 patients from 9 secondary care dermatology clinics over 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n = 53) had weekly follow-up assessments. Standard care clinical contacts were: general practitioner (7 visits; 1.2%), community nurse (169; 28.5%), practice nurse visits (189; 31.8%) and dermatology clinic visits (138; 23.2%). Participants whose wounds healed (34 of 45; 75.6%) attended an optional clinic visit. CONCLUSION: Data were obtained to inform a future RCT. Recruitment rates were found to be higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.

Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 1: a multicentre prospective observational cohort study in patients without planned compression.

BACKGROUND: There is no agreed treatment pathway following excision of keratinocyte cancer (KC). Compression therapy is considered beneficial for secondary intention healing on the lower leg; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. We report a multicentre prospective observational cohort study in this patient population with the intention of informing a future trial design. AIM: To estimate the time to healing in wounds healing by secondary intention without planned postoperative compression, following excision of KC on the lower leg; to characterize the patient population, including factors affecting healing; and to assess the incidence of complications. METHODS: This was a multicentre prospective observational cohort study. Inclusion criteria were age ≥ 18 years with planned excision of KC on the lower leg and healing by secondary intention, an ankle-brachial pressure index (ABPI) of ≥ 0.8; and written informed consent. Exclusion criteria included planned excision with primary closure, skin graft or flap; compression therapy for another indication; planned compression; inability of patient to receive, comply with or tolerate high compression; or a suspected diagnosis other than KC. RESULTS: This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n = 53), mean age was 81 years (range 25-97 years), median time to healing was 81 days (95% CI 73-92) and 45 patients (84.9%) had healing of the wound at the 6-month follow-up. The healing prognostic factors were wound parameters and ABPI. Wound infections occurred in 16 participants (30.2%). Four patients (7.5%) were admitted to hospital; three because of an infection and one because of a fall. CONCLUSIONS: The collected data have informed the RCT preparation. A relatively high proportion (7.5-15%) of unhealed wounds, infection and hospital admissions demonstrate the need for clearly establishing potentially effective treatments to improve outcomes for this population.

Sunproofed study protocol: A mixed-methods scoping study of sun safety policies in primary schools in Wales.

BACKGROUND: Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. AIMS: Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. METHODS: Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. DISCUSSION: Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.

A multicentre qualitative study of patient skin surgery experience during the COVID-19 pandemic in the UK.

Understanding patient concerns regarding skin surgery during the COVID-19 pandemic is a vital way of learning from individual experiences. A shift towards using superficial absorbable sutures (AS) has been anecdotally observed. We explored patient attitudes to the use of AS, and their experiences and perceptions of attending for skin surgery during the pandemic. In total, 35 participants were interviewed (74% men, 100% white British; mean age 72.5 years, range 43-95 years). Participants reported that they were reassured by precautions taken to minimize exposure and risk from COVID-19. The majority (86%) did not feel that personal protective equipment worn by staff impaired their experience, and 29% reported that their experience of attending for skin surgery during the lockdown period was more efficient and organized than on prepandemic visits. The vast majority (94%) of participants would opt to have AS again or had no strong preference for either suture type. Based on their experiences, most participants would have no concerns about attending for further skin surgery during the pandemic and would opt to have AS.

Use of perioperative prophylactic antibiotics following excision of ulcerated skin lesions in the UK: a national, multispeciality survey of clinicians.

Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice.

Engineering Cancer Antigen-Specific T Cells to Overcome the Immunosuppressive Effects of TGF-ß.

Adoptive T cell therapy with T cells expressing affinity-enhanced TCRs has shown promising results in phase 1/2 clinical trials for solid and hematological tumors. However, depth and durability of responses to adoptive T cell therapy can suffer from an inhibitory tumor microenvironment. A common immune-suppressive agent is TGF-ß, which is secreted by tumor cells and cells recruited to the tumor. We investigated whether human T cells could be engineered to be resistant to inhibition by TGF-ß. Truncating the intracellular signaling domain from TGF-ß receptor (TGFßR) II produces a dominant-negative receptor (dnTGFßRII) that dimerizes with endogenous TGFßRI to form a receptor that can bind TGF-ß but cannot signal. We previously generated specific peptide enhanced affinity receptor TCRs recognizing the HLA-A*02-restricted peptides New York esophageal squamous cell carcinoma 1 (NY-ESO-1)157-165/l-Ag family member-1A (TCR: GSK3377794, formerly NY-ESO-1c259) and melanoma Ag gene A10254-262 (TCR: ADP-A2M10, formerly melanoma Ag gene A10c796). In this article, we show that exogenous TGF-ß inhibited in vitro proliferation and effector functions of human T cells expressing these first-generation high-affinity TCRs, whereas inhibition was reduced or abolished in the case of second-generation TCRs coexpressed with dnTGFßRII (e.g., GSK3845097). TGF-ß isoforms and a panel of TGF-ß-associated genes are overexpressed in a range of cancer indications in which NY-ESO-1 is commonly expressed, particularly in synovial sarcoma. As an example, immunohistochemistry/RNAscope identified TGF-ß-positive cells close to T cells in tumor nests and stroma, which had low frequencies of cells expressing IFN-γ in a non-small cell lung cancer setting. Coexpression of dnTGFßRII may therefore improve the efficacy of TCR-transduced T cells.

SENTINEL COYOTE PATHOGEN SURVEY TO ASSESS DECLINING BLACK-FOOTED FERRET (MUSTELA NIGRIPES) POPULATION IN SOUTH DAKOTA, USA.

As part of the national recovery effort, endangered black-footed ferrets (Mustela nigripes) were reintroduced to the Cheyenne River Sioux Reservation in South Dakota, US in 2000. Despite an encouraging start, numbers of ferrets at the site have declined. In an effort to determine possible causes of the population decline, we undertook a pathogen survey in 2012 to detect exposure to West Nile virus (WNV), canine distemper virus (CDV), plague (Yersinia pestis), tularemia (Francisella tularensis), and heartworm (Dirofilaria immitis) using coyotes (Canis latrans) as a sentinel animal. The highest seroprevalence was for WNV with 71% (20/28) of coyotes testing antibody-positive. Seroprevalence of CDV and plague were lower, 27% and 13%, respectively. No evidence of active infection with tularemia or heartworm was seen in the coyotes sampled. As this study did not sample black-footed ferrets themselves, the definitive cause for the decline of this population cannot be determined. However, the presence of coyotes seropositive for two diseases, plague and CDV, lethal to black-footed ferrets, indicated the potential for exposure and infection. The high seroprevalence of WNV in the coyotes indicated a wide exposure to the virus; therefore, exposure of black-footed ferrets to the virus is also likely. Due to the ability of WNV to cause fatal disease in other species, studies may be useful to elucidate the impact that WNV could have on the success of reintroduced black-footed ferrets as well as factors influencing the spread and incidence of the disease in a prairie ecosystem.