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ObjectiveTo examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.DesignRetrospective cohort study.SettingRoutinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.ParticipantsAll adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.Primary outcomePoint prevalence of HIV.ResultsThere were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).ConclusionsThe prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.

The natural product lupeol (1) was isolated from Bombax ceiba leaves, which were used as starting material in the semisynthetic approach. Three new derivatives (2a, 2b, and 3) were synthesized using oxidation and aldolization. Their chemical structures were elucidated by spectroscopic analyses (HRESIMS and NMR). Compounds 3 showed significant α-glucosidase inhibition with an IC50 value of 202 µM, whereas 2a and 2b were inactive.

BackgroundHuman papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase.MethodsTotal numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination.ResultsOverall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC.ConclusionsHPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.

IntroductionMSM are at high risk for HPV infection and associated disease (genital warts and anal, oropharyngeal, and penile cancers). Additionally, MSM will receive little or no herd protection from the existing national vaccination programme for females. Following Joint Committee on Vaccination and Immunisation (JCVI) advice, a targeted HPV MSM vaccination pilot was introduced in GUM and HIV clinics across England from June 2016. We present plans for monitoring vaccination uptake and surveillance of infection and early disease outcomes.MethodsUptake (of three doses over a two year period) will be monitored via two existing surveillance and reporting systems: the Genitourinary medicine clinic activity dataset (GUMCADv2) and the HIV and AIDS reporting system (HARS). A seroprevalence study conducted in selected clinics for validation of these data will be considered in due course.Early impact of targeted HPV vaccination of MSM on the epidemiology of HPV infection will be detected by HPV DNA testing of rectal swabs (residual specimens following chlamydia testing) from MSM attending selected GUM clinics, starting with largely baseline collection in 2017.Expected early effects on genital warts diagnoses will be monitored (via GUMCADv2). A decline in HPV-associated cancers is not expected to be seen for some years.DiscussionA comprehensive surveillance strategy has been established to evaluate targeted HPV vaccination of MSM at GUM/HIV clinics. During the pilot, uptake will be the main outcome measure available, and surveillance systems will be established and baseline data collected to evaluate the outcomes of national implementation on infection and disease.

BACKGROUNDLittle is known about retention in human immunodeficiency virus (HIV) care in HIV-positive women after pregnancy in the United Kingdom. We explored the association between loss to follow-up (LTFU) in the year after pregnancy, maternal place of birth and duration of UK residence, in HIV-positive women in England, Wales, and Northern Ireland. METHODSWe analyzed combined data from 2 national data setsthe National Study of HIV in Pregnancy and Childhood; and the Survey of Prevalent HIV Infections Diagnosed, including pregnancies in 2000 to 2009 in women with diagnosed HIV. Logistic regression models were fitted with robust standard errors to estimate adjusted odds ratios (AOR). RESULTSOverall, 902 of 7211 (12.5%) women did not access HIV care in the year after pregnancy. Factors associated with LTFU included younger age, last CD4 in pregnancy of 350 cells/μL or greater and detectable HIV viral load at the end of pregnancy (all P < 0.001). On multivariable analysis, LTFU was more likely in sub-Saharan Africa-born (SSA-born) women than white UK-born women (AOR, 2.17; 95% confidence interval, 1.50–3.14; P < 0.001). The SSA-born women who had migrated to the UK during pregnancy were 3 times more likely than white UK-born women to be lost to follow-up (AOR, 3.19; 95% confidence interval, 1.94–3.23; P < 0.001). CONCLUSIONSOne in 8 HIV-positive women in England, Wales, and Northern Ireland did not return for HIV care in the year after pregnancy, with SSA-born women, especially those who migrated to the United Kingdom during pregnancy, at increased risk. Although emigration is a possible explanatory factor, disengagement from care may also play a role.

The self-timed (or asynchronous) approach to circuit design has demonstrated benefits in a number of different areas for its low energy consumption, high operating speed, composability, and modularity. Nonetheless, the asynchronous paradigm exposes challenges that are not found in the synchronous (or clock-driven) paradigm. For the verification task, a challenge emerges from the large number of potential operational interleavings exhibited in the asynchronous paradigm. Simply exploring all interleavings is, in general, intractable because the number of interleavings can grow exponentially.This dissertation focuses on developing scalable methods that are capable of reasoning effectively about the interleaving problem exhibited in self-timed systems. We specify and verify finite-state-machine representations of self-timed circuit designs using the DE system, a formal hardware description language defined using the ACL2 theorem-proving system. We apply a link-joint paradigm to model self-timed circuits as networks of channels that communicate with each other locally via handshake protocols. This link-joint model has been shown to be a universal model for various self-timed circuit families. In addition, this model has a clean formalization in the ACL2 logic and provides a protocol level that abstracts away timing constraints at the circuit level.Unlike many efforts for validating timing and communication properties of self-timed systems, we are interested in verifying functional properties. Specifically, we verify the functional correctness of self-timed systems in terms of relationships between their input and output sequences. To mitigate the consideration of all interleavings simultaneously, we address the verification problem hierarchically and avoid exploring the internal structures of verified submodules as well as their operational interleavings. The input-output relationship of a verified submodule is determined based on the communication signals at the submodule's input and output ports, while abstracting away all execution paths internal to that submodule.

This volume contains a selection of papers presented at the 17th International Workshop on the ACL2 Theorem Prover and its Applications (ACL2 2022). The workshops are the premier technical forum for presenting research and experiences related to ACL2.

We formalize some basic properties of Fourier series in the logic of ACL2(r), which is a variant of ACL2 that supports reasoning about the real and complex numbers by way of non-standard analysis. More specifically, we extend a framework for formally evaluating definite integrals of real-valued, continuous functions using the Second Fundamental Theorem of Calculus. Our extended framework is also applied to functions containing free arguments. Using this framework, we are able to prove the orthogonality relationships between trigonometric functions, which are the essential properties in Fourier series analysis. The sum rule for definite integrals of indexed sums is also formalized by applying the extended framework along with the First Fundamental Theorem of Calculus and the sum rule for differentiation. The Fourier coefficient formulas of periodic functions are then formalized from the orthogonality relations and the sum rule for integration. Consequently, the uniqueness of Fourier sums is a straightforward corollary. We also present our formalization of the sum rule for definite integrals of infinite series in ACL2(r). Part of this task is to prove the Dini Uniform Convergence Theorem and the continuity of a limit function under certain conditions. A key technique in our proofs of these theorems is to apply the overspill principle from non-standard analysis.

Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases.