Position statement and considerations for remotely delivered pulmonary rehabilitation services.

Statement and methods of development The challenge of access to pulmonary rehabilitation (PR) and meeting associated service demand is certainly not new. However, the COVID-19 pandemic set an unprecedented challenge evoking rapid adaptation of services. An inherent spotlight has been placed on remotely delivered services. As we look beyond the height of this pandemic, it is important to reflect and consider what has been learnt, and emerging perspectives on the future of PR service delivery. This document updates the ‘ACPRC statement and considerations for the remote delivery of pulmonary rehabilitation services during the COVID-19 pandemic’ (1) and seeks to provide pragmatic practical guidance for remotely delivered models of PR for healthcare professionals that should be used alongside local guidance. The recommendations provided are for guidance only, and may be updated in response to further national guidelines and new evidence. An online survey of PR healthcare professionals (ACPRC pulmonary rehabilitation provision during COVID-19 and beyond!) was conducted in the development of this document to scope current practice in PR services across the U.K. Informed by queries received by the ACPRC, the survey was first conducted in 2020 and repeated in July 2021 with the aim of capturing a snapshot of practice, one-year post onset of the COVID-19 pandemic. The survey was publicised and disseminated via Twitter using the @theACPRC handle, with request that one team member completed on behalf of their service. A summary of the 21 responses can be found in Appendix 1 which served to inform the content of this document. A literature review was undertaken to identify and integrate relevant published trials since the 2021 Cochrane review of telerehabilitation for people with chronic respiratory disease (2). Details of the search strategy can be found in Appendix 2 and summary of study characteristics and outcomes in Appendix 3. Anonymous feedback from four PR services was collated and analysed to identify common themes in experiences of remotely delivered PR services. A summary of this process and collated feedback can be found in Appendix 4. Key terms Remotely delivered models – the delivery of pulmonary rehabilitation services at a distance; the interaction between healthcare professional and participant using communication and information technologies, that may take place in real-time (synchronously) or asynchronously (1). It may be delivered by a virtual platform, an online web application or programme, or referred to as telerehabilitation (note: this terminology is used where studies have reported it). Field walking tests are commonly employed to evaluate exercise capacity, prescribe exercise, and evaluate treatment response in chronic respiratory diseases (3). The most valid, reliable and responsive ones are the six-minute walk test (6MWT), incremental (ISWT) and endurance walk test (ESWT). NACAP – the National Asthma and COPD Audit Programme is commissioned by the Healthcare Quality Improvement Partnership (HQIP), as part of the National Clinical Audit and Patient Outcomes Programme (NCAPOP), and currently covers England and Wales. The programme is led by the Royal College of Physicians (RCP) and includes a pulmonary rehabilitation workstream. PRSAS – the Pulmonary Rehabilitation Services Accreditation Scheme was launched in April 2018, and is run by the Royal College of Physicians (RCP)

University for the Creative Arts staff research 2011

This publication brings together a selection of the University’s current research. The contributions foreground areas of research strength including still and moving image research, applied arts and crafts, as well as emerging fields of investigations such as design and architecture. It also maps thematic concerns across disciplinary areas that focus on models and processes of creative practice, value formations and processes of identification through art and artefacts as well as cross-cultural connectivity. Dr. Seymour Roworth-Stoke

SCOPE New Photographic Practices

The photographic practices brought together for this exhibition and publication provide a broad scope of how photographic and lens based media may be used in order to have a visceral and conceptual impact. The methods on show demonstrate the way that artists might pick and choose from the approaches, processes and debates that have arisen through the medium’s history. This collection of work features film, video and photography that demand a renegotiation of the relationship between camera, subject and viewer. Visual Art Centre Gallery, Tsinghua University, Beijing, Chin

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses

Ajuts: R01/R56 NIH Grant AI-52779 (GDT), NIH F31 Fellowship (1F31AI106519-01)(TLP), Center for AIDS Research (P30 AI 64518) i Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, grant number UM1-AI100645-01 (AM)Abstract.Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called "beneficial" regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control

Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called “beneficial” regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control

Individual Health Trainers to support health and wellbeing for people under community supervision in the criminal justice system: the STRENGTHEN pilot RCT

No embargo require

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations