A single synthetic lipid antigen for improved serological diagnosis of Buruli ulcer.

SETTING: The diagnosis of Buruli ulcer (BU) is frequently made by experienced health workers in rural regions. This leads to long turnaround times to confirm the diagnosis as it requires specialised laboratory infrastructure to perform confirmatory testing. BACKGROUND: Given the lack of success with protein antigens to detect BU in human sera, the aim of this study was to evaluate a range of single synthetic lipid antigens using an enzyme-linked immunosorbent assay (ELISA). The ELISA system used was initially developed to detect TB using single synthetic lipid antigens. METHODS: Thirty polymerase chain reaction (PCR) positive BU samples and 30 PCR-negative healthy contact samples collected from Asante Akim North and Ahafo Ano North Districts, Ghana, that are endemic for BU between 2013 and 2016 were used to evaluate the synthetic lipid antigen ELISA. A Quantikine ELISA was also conducted on a randomly blinded sub-set of 30 samples. RESULTS: The synthetic lipid ELISA evaluated here outperforms all other ELISA tests using protein antigens to detect BU to date and has shown potential as a fast (2 h) test for BU which may be adapted for use at the point of care. A sensitivity of 63% and specificity of 80% was observed for 30 BU-positive and 30 BU-negative samples, with significantly reduced interleukin-8 (IL-8) levels in a subset of patients with BU. CONCLUSION: A single lipid was shown for the first time to have the ability to distinguish between PCR-positive BU and negative sera using ELISA. The low lipid antibody load detected may be a result of immune suppression caused by the presence of mycolactone in patients with BU, given that levels of IL-8 were significantly reduced in patients with BU compared to the control serum samples.

Modeling Global Carbon Costs of Plant Nitrogen and Phosphorus Acquisition.

Most Earth system models (ESMs) do not explicitly represent the carbon (C) costs of plant nutrient acquisition, which leads to uncertainty in predictions of the current and future constraints to the land C sink. We integrate a plant productivity-optimizing nitrogen (N) and phosphorus (P) acquisition model (fixation & uptake of nutrients, FUN) into the energy exascale Earth system (E3SM) land model (ELM). Global plant N and P uptake are dynamically simulated by ELM-FUN based on the C costs of nutrient acquisition from mycorrhizae, direct root uptake, retranslocation from senescing leaves, and biological N fixation. We benchmarked ELM-FUN with three classes of products: ILAMB, a remotely sensed nutrient limitation product, and CMIP6 models; we found significant improvements in C cycle variables, although the lack of more observed nutrient data prevents a comprehensive level of benchmarking. Overall, we found N and P co-limitation for 80% of land area, with the remaining 20% being either predominantly N or P limited. Globally, the new model predicts that plants invested 4.1 Pg C yr-1 to acquire 841.8 Tg N yr-1 and 48.1 Tg P yr-1 (1994-2005), leading to significant downregulation of global net primary production (NPP). Global NPP is reduced by 20% with C costs of N and 50% with C costs of NP. Modeled and observed nutrient limitation agreement increases when N and P are considered together (r 2 from 0.73 to 0.83).

FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study.

BACKGROUND: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone. METHODS: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing. DISCUSSION: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence. TRIAL REGISTRATION: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021.

Variation in blood mercury concentrations in brown skuas (Stercorarius antarcticus) is related to trophic ecology but not breeding success or adult body condition.

Mercury is a pervasive environmental contaminant that can negatively impact seabirds. Here, we measure total mercury (THg) concentrations in red blood cells (RBCs) from breeding brown skuas (Stercorarius antarcticus) (n = 49) at Esperanza/Hope Bay, Antarctic Peninsula. The aims of this study were to: (i) analyse RBCs THg concentrations in relation to sex, year and stable isotope values of carbon (δ13C) and nitrogen (δ15N); and (ii) examine correlations between THg, body condition and breeding success. RBC THg concentrations were positively correlated with δ15N, which is a proxy of trophic position, and hence likely reflects the biomagnification process. Levels of Hg contamination differed between our study years, which is likely related to changes in diet and distribution. RBC THg concentrations were not related to body condition or breeding success, suggesting that Hg contamination is currently not a major conservation concern for this population.

Varying aerobic capacity in relation to breeding stage and reproductive success in giant petrels (Macronectes spp.).

Reproduction, and parental care in particular, are among the most energy-demanding activities within the annual cycle of adult birds. Parents that cannot meet the metabolic demands and other physiological costs of raising offspring may opt to abandon chicks in favour of self-maintenance and future reproduction. Recent work examining reproductive trade-offs in birds revealed an important role of oxygen carrying capacity in mediating variation in parental effort. This study explores the aerobic factors underlying the success or failure of parental care in two closely-related petrel species during their breeding season on Bird Island, South Georgia: northern giant petrels (Macronectes halli) and southern giant petrels (M. giganteus). Failed breeders of both sexes and species had significantly lower hematocrit levels (by 5.48 ± 0.64%) than successful breeders, and reticulocyte counts also tended to be lower in failed males, consistent with the hypothesis that parental care and workload depend on aerobic capacity. We discuss these results in relation to differences in the foraging ecology of both species and sexes.

Pregnancy rates and outcomes in women with cystic fibrosis in the UK: comparisons with the general population before and after the introduction of disease-modifying treatment, 2003-17.

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment. DESIGN: A population-based longitudinal study, 2003-17. SETTING: United Kingdom. POPULATION: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. METHODS: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age. MAIN OUTCOME MEASURES: Pregnancy and live-birth rates and child gestational age. RESULTS: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age. CONCLUSIONS: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor. TWEETABLE ABSTRACT: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate.

Bad bugs: antibiotic-resistant bacteriuria in pregnancy and risk of pyelonephritis.

BACKGROUND: The introduction of antibiotics has significantly reduced morbidity and mortality from microbial infections, but the rise of antibiotic-resistant and multidrug-resistant microbes is of increasing clinical concern. Few studies have examined the prevalence and impact of antibiotic resistance in common antenatal infections. OBJECTIVE: This study aimed to determine whether pregnant women with a urine culture positive for antibiotic-resistant or multidrug-resistant gram-negative bacteria are at increased risk of developing pyelonephritis than pregnant women infected with antibiotic-susceptible organisms. STUDY DESIGN: This was a retrospective cohort study of pregnant women with asymptomatic bacteriuria or acute cystitis from a single health system from July 2013 to May 2019. Women with gram-negative antibiotic-resistant (resistance to 1-2 antibiotic classes) and multidrug-resistant (resistance to ≥3 antibiotic classes) lower urinary tract infections were compared with women with antibiotic-susceptible urinary tract infections in terms of demographic, infectious, antepartum, and intrapartum data. The primary outcome was pyelonephritis, defined as a billing code for pyelonephritis plus fever or flank pain. The secondary outcomes were length of stay in the hospital because of pyelonephritis, a composite of pyelonephritis complications (renal abscess, sepsis, and intensive care unit admission), and preterm delivery. The differences in the primary outcome were analyzed using multivariate logistic regression. RESULTS: A total of 573 women were eligible for inclusion. Of the 573 women, 334 (58%) had gram-negative bacteria on urine culture. Of the 334 cases, 173 (52%) were antibiotic susceptible, 74 (22%) were antibiotic resistant, and 87 (26%) were multidrug resistant. Women with antibiotic-resistant and multidrug-resistant infections were more likely to have hypertension (P=.004), to be Black (P=.03), to have public insurance (P=.002), and to experience more urinary infections (P=.001). Pyelonephritis was more common in women with antibiotic-resistant (adjusted odds ratio, 2.27; 95% confidence interval, 1.08-4.78) and multidrug-resistant (adjusted odds ratio, 3.06; 95% confidence interval, 1.57-5.96) infections than in women with antibiotic-susceptible urinary tract infections. Length of stay, preterm delivery, and pyelonephritis complications did not differ between antibiotic-susceptible and antibiotic-resistant and multidrug-resistant infections. CONCLUSION: In an age of increasing antibiotic resistance, more than one-half of pregnant women with bacteriuria experience at least 1 infection with an antibiotic-resistant organism. These resistance patterns have a real clinical impact as pregnant women with antibiotic-resistant gram-negative lower urinary tract infections have an estimated 2- to 3-fold increased odds of developing pyelonephritis.

Rabies is still a fatal but neglected disease: a case report.

BACKGROUND: Rabies, caused by a lyssavirus, is a viral zoonosis that affects people in many parts of the world, especially those in low income countries. Contact with domestic animals, especially dogs, is the main source of human infections. Humans may present with the disease only after a long period of exposure. Nearly half of rabies cases occur in children <15 years old. We report on a fatal case of rabies in a Ghanaian school child 5 years after the exposure incident, and the vital role of molecular tools in the confirmation of the diagnosis. CASE PRESENTATION: The patient, an 11-year-old junior high school Ghanaian student from the Obuasi Municipality in Ghana, presented with aggressive behavior, which rapidly progressed to confusion and loss of consciousness within a day of onset. Her parents reported that the patient had experienced a bite from a stray dog on her right leg 5 years prior to presentation, for which no antirabies prophylaxis was given. The patient died within minutes of arrival in hospital (within 24 hours of symptom onset). Real-time polymerase chain reaction testing of cerebrospinal fluid obtained after her death confirmed the diagnosis of rabies. Subsequent phylogenetic analysis showed the virus to belong to the Africa 2 lineage of rabies viruses, which is one of the predominant circulating lineages in Ghana. CONCLUSION: The incubation period of rabies is highly variable so patients may only present with symptoms long after the exposure incident. Appropriate molecular testing tools, when available as part of rabies control programmes, are vital in confirming cases of rabies.

Pollination by nectar-foraging pompilid wasps: a new specialized pollination strategy for the Australian flora.

The Pompilidae is a cosmopolitan and diverse group of wasps, which commonly feed on nectar. However, pollination systems specialized on pompilids have not been documented in detail outside of southern Africa. Here, we studied Caladenia drummondii (Orchidaceae) where, based on floral traits and preliminary field observations, we predicted pollination by sexual deception of male pompilid wasps. Detailed pollinator observations were undertaken using floral baiting experiments at sites spanning 375 km. Following evidence for nectar on some flowers of C. drummondii, the sugar content on the labellum was analysed by GC-MS. Floral spectral reflectance was measured and compared with Caladenia using other pollination strategies. Males of a single species of pompilid wasp (Calopompilus sp.) were the only visitors capable of pollinating C. drummondii. Attempts to feed from the surface of the labellum were frequent and were associated with removal and deposition of pollinia. GC-MS analysis revealed larger quantities of sugar on the labellum than reported in other Caladenia species. While no sexual or courtship behaviour was observed, the zig-zag and circling flight on approach to the flower is suggestive of odour-based attraction. Floral spectral reflectance was similar to sexually deceptive Caladenia. This study represents the first confirmation of a specialized pompilid pollination system outside of Africa. Although pollination occurs during nectar-foraging, long-distance sexual attraction cannot be ruled out as an explanation for the exclusive male visitation. The similarity in floral spectral reflectance to other Caladenia indicates colour may not impose a constraint on the evolution of pollination by pompilids.

A trade-off between plant and soil carbon storage under elevated CO2.

Terrestrial ecosystems remove about 30 per cent of the carbon dioxide (CO2) emitted by human activities each year1, yet the persistence of this carbon sink depends partly on how plant biomass and soil organic carbon (SOC) stocks respond to future increases in atmospheric CO2 (refs. 2,3). Although plant biomass often increases in elevated CO2 (eCO2) experiments4-6, SOC has been observed to increase, remain unchanged or even decline7. The mechanisms that drive this variation across experiments remain poorly understood, creating uncertainty in climate projections8,9. Here we synthesized data from 108 eCO2 experiments and found that the effect of eCO2 on SOC stocks is best explained by a negative relationship with plant biomass: when plant biomass is strongly stimulated by eCO2, SOC storage declines; conversely, when biomass is weakly stimulated, SOC storage increases. This trade-off appears to be related to plant nutrient acquisition, in which plants increase their biomass by mining the soil for nutrients, which decreases SOC storage. We found that, overall, SOC stocks increase with eCO2 in grasslands (8 ± 2 per cent) but not in forests (0 ± 2 per cent), even though plant biomass in grasslands increase less (9 ± 3 per cent) than in forests (23 ± 2 per cent). Ecosystem models do not reproduce this trade-off, which implies that projections of SOC may need to be revised.

Timing of the martian dynamo: New constraints for a core field 4.5 and 3.7 Ga ago.

The absence of crustal magnetic fields above the martian basins Hellas, Argyre, and Isidis is often interpreted as proof of an early, before 4.1 billion years (Ga) ago, or late, after 3.9 Ga ago, dynamo. We revisit these interpretations using new MAVEN magnetic field data. Weak fields are present over the 4.5-Ga old Borealis basin, with the transition to strong fields correlated with the basin edge. Magnetic fields, confined to a near-surface layer, are also detected above the 3.7-Ga old Lucus Planum. We conclude that a dynamo was present both before and after the formation of the basins Hellas, Utopia, Argyre, and Isidis. A long-lived, Earth-like dynamo is consistent with the absence of magnetization within large basins if the impacts excavated large portions of strongly magnetic crust and exposed deeper material with lower concentrations of magnetic minerals.

Do genetic variations in proximal tubule transporters influence tenofovir-induced renal dysfunction? An exploratory study in a Ghanaian population.

OBJECTIVES: To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters. PATIENTS AND METHODS: The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05). RESULTS: None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, ß= -0.4), higher baseline CLCR (P = 0.008, ß = 65.2) and lower CLCR after 1 year (P = 0.024, ß= -26.6). CONCLUSIONS: This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort.

A specialised pollination system using nectar-seeking thynnine wasps in Caladenia nobilis (Orchidaceae).

Caladenia is a diverse Australian genus that is exceptional among orchids in having both species pollinated by food-seeking and sexually deceived insects. Here, we investigated the pollination of Caladenia nobilis, a species predicted to be food-deceptive due to its large, cream-coloured and apparently nectarless flowers. Pollinator observations were made using experimental clumps of flowers. Measurements of floral colour were undertaken with a spectrometer, nectar was tested using GC-MS, and reproductive success was quantified for 2 years. While C. nobilis attracted nine species of insect, only males of the thynnine wasp Rhagigaster discrepans exhibited the correct size and behaviour to remove and deposit pollen. Male R. discrepans attempted to feed from the surface of the labellum, often crawling to multiple flowers, but showed no evidence of sexual attraction. Most flowers produced little or no nectar, although some may provide enough sucrose to act as a meagre reward to pollinators. Floral colouration was similar to a related Caladenia species pollinated by sexual deception, although the sexually deceptive species had a dull-red labellum. Reproductive success was generally low and highly variable between sites and years. In addition to most visitors being of inappropriate size for pollinia removal, the lack of response to the orchid by several co-occurring species of thynnine wasp suggests filtering of potential pollinators at the attraction phase. Our discovery of a pollination strategy that may be intermediate between food deception and food reward raises the question, how many putatively rewardless orchids actually produce meagre amounts of nectar?

Successful development of methodology for detection of hapten-specific contact hypersensitivity (CHS) memory in swine.

Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the "adaptive" characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system.

Providing insight into the incubation period of Mycobacterium ulcerans disease: two case reports.

BACKGROUND: Buruli ulcer caused by Mycobacterium ulcerans is endemic in parts of West Africa and is most prevalent among the 5-15 years age group; Buruli ulcer is uncommon among neonates. The mode of transmission and incubation period of Buruli ulcer are unknown. We report two cases of confirmed Buruli ulcer in human immunodeficiency virus-unexposed, vaginally delivered term neonates in Ghana. CASE PRESENTATION: Patient 1: Two weeks after hospital delivery, a baby born to natives of the Ashanti ethnic group of Ghana was noticed by her mother to have a papule with associated edema on the right anterior chest wall and neck that later ulcerated. There was no restriction of neck movements. The diagnosis of Buruli ulcer was confirmed on the basis of a swab sample that had a positive polymerase chain reaction result for the IS2404 repeat sequence of M. ulcerans. Patient 2: This patient, from the Ashanti ethnic group in Ghana, had the mother noticing a swelling in the baby's left gluteal region 4 days after birth. The lesion progressively increased in size to involve almost the entire left gluteal region. Around the same time, the mother noticed a second, smaller lesion on the forehead and left side of neck. The diagnosis of Buruli ulcer was confirmed by polymerase chain reaction when the child was aged 4 weeks. Both patients 1 and 2 were treated with oral rifampicin and clarithromycin at recommended doses for 8 weeks in addition to appropriate daily wound dressing, leading to complete healing. Our report details two cases of polymerase chain reaction-confirmed Buruli ulcer in children whose lesions appeared at ages 14 and 4 days, respectively. The mode of transmission of M. ulcerans infection is unknown, so the incubation period is difficult to estimate and is probably dependent on the infective dose and the age of exposure. In our study, lesions appeared 4 days after birth in patient 2. Unless the infection was acquired in utero, this would be the shortest incubation period ever recorded. CONCLUSIONS: Buruli ulcer should be included in the differential diagnosis of neonates who present with characteristic lesions. The incubation period of Buruli ulcer in neonates is probably shorter than is reported for adults.

Cellular Uptake and Efflux of Palbociclib In Vitro in Single Cell and Spheroid Models.

Adequate drug distribution through tumors is essential for treatment to be effective. Palbociclib is a cyclin-dependent kinase 4/6 inhibitor approved for use in patients with hormone receptor positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. It has unusual physicochemical properties, which may significantly influence its distribution in tumor tissue. We studied the penetration and distribution of palbociclib in vitro, including the use of multicellular three-dimensional models and mathematical modeling. MCF-7 and DLD-1 cell lines were grown as single cell suspensions (SCS) and spheroids; palbociclib uptake and efflux were studied using liquid chromatography-tandem mass spectrometry. Intracellular concentrations of palbociclib for MCF-7 SCS (C max 3.22 µM) and spheroids (C max 2.91 µM) were 32- and 29-fold higher and in DLD-1, 13- and 7-fold higher, respectively, than the media concentration (0.1 µM). Total palbociclib uptake was lower in DLD-1 cells than MCF-7 cells in both SCS and spheroids. Both uptake and efflux of palbociclib were slower in spheroids than SCS. These data were used to develop a mathematical model of palbociclib transport that quantifies key parameters determining drug penetration and distribution. The model reproduced qualitatively most features of the experimental data and distinguished between SCS and spheroids, providing additional support for hypotheses derived from the experimental data. Mathematical modeling has the potential for translating in vitro data into clinically relevant estimates of tumor drug concentrations. SIGNIFICANCE STATEMENT: This study explores palbociclib uptake and efflux in single cell suspension and spheroid models of cancer. Large intracellular concentrations of palbociclib are found after drug exposure. The data from this study may aid understanding of the intratumoural pharmacokinetics of palbociclib, which is useful in understanding how drug distributes within tumor tissue and optimizing drug efficacy. Biomathematical modelling has the potential to derive intratumoural drug concentrations from plasma pharmacokinetics in patients.

'Test n Treat' (TnT): a cluster randomized feasibility trial of on-site rapid Chlamydia trachomatis tests and treatment in ethnically diverse, sexually active teenagers attending technical colleges.

OBJECTIVES: We conducted a cluster-randomized feasibility trial of 90-minute Chlamydia trachomatis tests and same day on-site treatment ('Test n Treat/TnT') in six technical colleges in London, England, to assess TnT uptake rates; follow-up rates; prevalence of C. trachomatis at baseline and 7 months; time to treatment; acceptability of TnT. METHODS: Participants completed questionnaires and provided genitourinary samples at baseline and 7 months. Participants were informed that baseline samples would not be tested for 7 months and were advised to get screened independently. Colleges were randomly allocated 1:1 to intervention (TnT) or control (no TnT). One month and 4 months post recruitment, participants at intervention colleges were texted invitations for on-site free C. trachomatis tests. A purposive sample of students who did/did not attend for screening were interviewed (n = 26). RESULTS: Five hundred and nine sexually active students were recruited: median age 17.9 years, 47% male, 50% black ethnicity, 55% reporting two or more sexual partners in the previous year. TnT uptake was 13% (33/259; 95% CI 8.9-17.4%) at 1 month and 10% (26/259; 6.7-14.4%) at 4 months with overall C. trachomatis positivity 5.1% (3/59; 1.1-14.2%). Follow-up at 7 months was 62% (317/509) for questionnaires and 52% (264/509) for samples. C. trachomatis prevalence was 6.2% (31/503) at baseline and 6.1% (16/264) at 7 months. Median time from test to treatment was 15 h. Interviews suggested low test uptake was associated with not feeling at risk, perceptions of stigma, and little knowledge of sexually transmitted infections (STIs). CONCLUSIONS: Despite high C. trachomatis rates at baseline and follow-up, uptake of testing was low. Like many countries, England urgently needs better sex education, including making STI testing routine/normal. Trial registration ISRCTN58038795.

The treatment of anal fistula: second ACPGBI Position Statement - 2018.

It is over 10 years since the first ACPGBI Position Statement on the management of anal fistula was published in 2007. This second edition is the result of scrutiny of the literature published during this time; it updates the original Position Statement and reviews the published evidence surrounding treatments for anal fistula that have been developed since the original publication.