Two Years Later: Journals Are Not Yet Enforcing the ARRIVE Guidelines on Reporting Standards for Pre-Clinical Animal Studies

There is growing concern that poor experimental design and lack of transparent reporting contribute to the frequent failure of pre-clinical animal studies to translate into treatments for human disease. In 2010, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were introduced to help improve reporting standards. They were published in PLOS Biology and endorsed by funding agencies and publishers and their journals, including PLOS, Nature research journals, and other top-tier journals. Yet our analysis of papers published in PLOS and Nature journals indicates that there has been very little improvement in reporting standards since then. This suggests that authors, referees, and editors generally are ignoring guidelines, and the editorial endorsement is yet to be effectively implemented

A national audit of the management pathways for new HIV diagnoses

The British HIV Association recommends that new diagnoses be reviewed by an HIV specialist within two weeks. NHS England outcome measures include the proportion of new diagnoses commencing antiretroviral therapy (ART) within 91 days. We aimed to review the extent to which these recommendations were followed, to explore the topics discussed with new diagnoses, and to identify reasons behind delayed ART initiation. UK specialist HIV services were invited to retrospectively review the notes of their last 40 new diagnoses over a 15-month period. One-hundred and thirty-two services provided data for 2281 eligible individuals. Most new diagnoses were reviewed by a specialist within two weeks (67.7%) and were commenced on ART within 91 days (83%), however, there were some concerning delays in those tested at home and in general practice. Partner notification and treatment benefits were discussed with most individuals, unlike the availability of community support and U = U (“undetectable equals untransmittable”). Lengthy delays in ART initiation were mostly due to individuals initially declining ART or missing appointments. Our findings suggest a need for more streamlined pathways into HIV care, review of new diagnoses who have not commenced ART within 8 weeks, and protocol development to ensure discussion of relevant topics

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/μL) and lowest in medical admissions/A&E (94 cells/μL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/μL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis.

Psoriatic arthritis (PsA) is a debilitating immune-mediated inflammatory arthritis of unknown pathogenesis commonly affecting patients with skin psoriasis. Here we use complementary single-cell approaches to study leukocytes from PsA joints. Mass cytometry demonstrates a 3-fold expansion of memory CD8 T cells in the joints of PsA patients compared to peripheral blood. Meanwhile, droplet-based and plate-based single-cell RNA sequencing of paired T cell receptor alpha and beta chain sequences show pronounced CD8 T cell clonal expansions within the joints. Transcriptome analyses find these expanded synovial CD8 T cells to express cycling, activation, tissue-homing and tissue residency markers. T cell receptor sequence comparison between patients identifies clonal convergence. Finally, chemokine receptor CXCR3 is upregulated in the expanded synovial CD8 T cells, while two CXCR3 ligands, CXCL9 and CXCL10, are elevated in PsA synovial fluid. Our data thus provide a quantitative molecular insight into the cellular immune landscape of psoriatic arthritis

EBI2 is highly expressed in multiple sclerosis lesions and promotes early CNS migration of encephalitogenic CD4 T cells

Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. EBI2 and its ligand, 7{alpha},25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7{alpha},25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23) and interleukin-1 beta (IL-1{beta}), maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhanced early migration of encephalitogenic T cells into the CNS in a transfer EAE model. Nonetheless, EBI2 was dispensable in active EAE. Human Th17 cells do also express EBI2, and EBI2 expressing cells are abundant within multiple sclerosis (MS) white matter lesions. These findings implicate EBI2 as a mediator of CNS autoimmunity and describe mechanistically its contribution to the migration of autoreactive T cells into inflamed organs