Induction of HIV-1 Gag-specific memory T cells in Chacma baboons by MVA prime and VLP boost vaccine regimen

We previously reported induction of HIV-specific responses in Chacma baboons following immunization with SAAVI MVA-C (MVA) and HIV-1 Pr55 Gag virus-like particles (VLPs) in a prime-boost vaccination strategy. In the current study, we characterised the vaccine specific memory T cells by flow cytometry

A pantothenate suxotroph of BCG rxpressing Gag confers enhanced HIV-specific immunogenicity compared to wildtype and perfingolysin expressing strains

In tuberculosis vaccine studies, perfingolysin expressing strains (pfo) of recombinant Mycobacterium bovis (rBCG) have been shown to enhance immunogenicity as compared to wildtype strains whilst pantothenate auxotrophic strains (ΔpanCD) have been shown to be safer and more immunogenic. Our group has recently shown that rBCGΔpanCD expressing HIV-1 Gag is more immunogenic than the wildtype Pasteur strain of BCG in the murine model. In this study, a wild type strain, a ΔpanCDstrain, a pfo strain and a ΔpanCD strain expressing perfringolysin (ΔpanCDpfo) of Danish BCG were used as vectors to express HIV-1 subtype C Gag. Gag specific immune responses induced by a prime with each rBCG-Gag vaccine and boost with modified vaccinia Ankara (MVA) were compared

Zonotopes and four-dimensional superconformal field theories

The a-maximization technique proposed by Intriligator and Wecht allows us to determine the exact R-charges and scaling dimensions of the chiral operators of four-dimensional superconformal field theories. The problem of existence and uniqueness of the solution, however, has not been addressed in general setting. In this paper, it is shown that the a-function has always a unique critical point which is also a global maximum for a large class of quiver gauge theories specified by toric diagrams. Our proof is based on the observation that the a-function is given by the volume of a three dimensional polytope called "zonotope", and the uniqueness essentially follows from Brunn-Minkowski inequality for the volume of convex bodies. We also show a universal upper bound for the exact R-charges, and the monotonicity of a-function in the sense that a-function decreases whenever the toric diagram shrinks. The relationship between a-maximization and volume-minimization is also discussed.Comment: 29 pages, 15 figures, reference added, typos corrected, version published in JHE

Exploring Cancer Outcomes of People With and Without Pre-existing Anxiety and/or Depression Following Symptomatic Presentation to Healthcare: A Scoping Review

What are the cancer outcomes in people with pre-existing anxiety and/or depression? A secondary aim is to explore the extent of evidence on possible reasons underlying differences in cancer outcomes between people with and without anxiety and/or depressionObjective: The objective of this scoping review is to collate the literature on cancer outcomes and highlight where any disparities occur for people with anxiety and/or depression, enabling exploration of the reasons behind those factors. Introduction: Around 375,000 people in the UK are diagnosed with cancer annually. Individuals with mental health disorders have a 30% higher case fatality rate from cancer compared to individuals without. Each year, 5-7% of urgent suspected-cancer hospital appointments are missed, with anxiety and depression possible causes, and survival is worse following emergency diagnoses. Inclusion criteria: Studies that report differences/disparities in cancer diagnostic processes/outcomes between people with/without pre-existing anxiety and/or depression will be included. Methods: The databases MEDLINE, PsycINFO, EMBASE and CINAHL will be searched for articles between 2015 and 2024. Additional articles will be sourced using forward and backward citations. Two researchers will screen the articles for eligibility against the inclusion criteria. Qualifying articles will be quality appraised. The search results will be presented using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR). The final articles will be presented in a narrative synthesis supplemented with thematic analysis if appropriate.National Institute for Health and Care Research (NIHR

An Overview of Antithrombotics in Ischemic Stroke

The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke

Autonomic dysregulation and self‐injurious thoughts and behaviours in children and young people: A systematic review and meta‐analysis

Background: self-injurious thoughts and behaviours (SITBs) have been associated with dysfunction of the Autonomic Nervous System (ANS) in children and young people, suggesting that objective ANS measures may aid assessment of suicide risk, but a systematic synthesis of this literature is currently lacking.Methods: following a pre-registered protocol (PROSPERO CRD42022327605), we conducted a systematic search of PubMed, Medline, Embase, PsycINFO, and Web of Science, for empirical studies published until 10th May 2022 that compared indices of ANS functioning in individuals aged 0–25 years with versus without SITBs, or reported continuous associations between ANS measures and SITBs. Study quality was assessed with the Newcastle-Ottawa Scales. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models.Results: twenty studies (1979 participants) were included in our systematic review, with 16 included in meta-analyses. Results suggested that SITBs were associated with altered cardiac indices of arousal (g = −0.328, p < 0.001), which was driven by lower heart rate variability in individuals with SITBs (g = −0.375, p = 0.025). Overall results for electrodermal activity were not significant (g = 0.026, p = 0.857), but subgroup analyses showed increased activity in studies of individuals who engaged specifically in non-suicidal self-harm (g = 0.249, p = 0.014) but decreased activity in the remaining studies (g = −0.567, p = 0.004).Conclusions: our systematic review and meta-analysis found evidence of reduced parasympathetic regulation as well as more tentative evidence of altered electrodermal activity in children and young people displaying SITBs. Future longitudinal studies should test the clinical utility of these markers for detecting and monitoring suicide risk

Intra-abdominal cancer risk with abdominal pain: a prospective cohort primary-care study

This is the author accepted manuscript. The final version is available from the Royal College of General Practitioners via the DOI in this record Background: Quantifying cancer risk in primary-care patients reporting abdominal pain would inform diagnostic strategies. Aim: To quantify oesophagogastric, colorectal, liver, pancreatic, ovarian, uterine, kidney and bladder cancer risks associated with newly reported abdominal pain with or without other symptoms, signs or abnormal blood tests (i.e. features) indicative of possible cancer. Design and setting: Observational prospective cohort study using Clinical Practice Research Datalink records with English cancer registry linkage. Methods: Participants (N=125,793) aged ≥40 years had newly reported abdominal pain in primary care during 01/01/2009-31/12/2013. The outcomes were 1-year cumulative incidence of cancer, and the composite 1-year cumulative incidence of cancers with shared additional features, stratified by age and sex. Results: With abdominal pain, overall risk was greater in men and increased with age, reaching 3.4% (95%CI 3.0–3.7%; predominantly colorectal cancer 1.9%, 1.6–2.1%) in men ≥70 years, compared with their expected incidence of 0.88% (0.87%–0.89%). Additional features increased cancer risk; for example, colorectal or pancreatic cancer risk with abdominal pain plus diarrhoea at 60–69 and ≥70, respectively, was 3.1% (1.9–4.9%) and 4.9% (3.7–6.4%), predominantly colorectal cancer (2.2%, 2–3.8% and 3.3%, 2.0–4.9%). Conclusions: Abdominal pain increases intra-abdominal cancer risk nearly fourfold in men aged ≥70, exceeding the 3% threshold warranting investigation. This threshold is surpassed for the over-60s only with additional features. These results help direct appropriate referral and testing strategies for patients based on their demographic profile and reporting features. We suggest non-invasive strategies first, such as faecal immunochemical testing, with safety-netting in a shared decision-making framework.National Institute for Health ResearchDepartment of Health and Social CareDennis and Mirelle Gillings Foundatio

Regular Incidence Complexes, Polytopes, and C-Groups

Regular incidence complexes are combinatorial incidence structures generalizing regular convex polytopes, regular complex polytopes, various types of incidence geometries, and many other highly symmetric objects. The special case of abstract regular polytopes has been well-studied. The paper describes the combinatorial structure of a regular incidence complex in terms of a system of distinguished generating subgroups of its automorphism group or a flag-transitive subgroup. Then the groups admitting a flag-transitive action on an incidence complex are characterized as generalized string C-groups. Further, extensions of regular incidence complexes are studied, and certain incidence complexes particularly close to abstract polytopes, called abstract polytope complexes, are investigated.Comment: 24 pages; to appear in "Discrete Geometry and Symmetry", M. Conder, A. Deza, and A. Ivic Weiss (eds), Springe

Symptom lead times in lung and colorectal cancers: What are the benefits of symptom-based approaches to early diagnosis?

This is the final version of the article. Available from Cancer Research UK via the DOI in this record.Background: Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood. Methods: We re-analysed a UK-based case-control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer. Results: Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27-48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12-32% with undiagnosed colorectal cancer are not caused by the cancer. Conclusions: In most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis.This work was supported by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme, RP-PG-0608-10045