COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus - and R. arrhizus -induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients

Plasma physics and control studies planned in JT-60SA for ITER and DEMO operations and risk mitigation

| openaire: EC/H2020/633053/EU//EUROfusionA large superconducting machine, JT-60SA has been constructed to provide major contributions to the ITER program and DEMO design. For the success of the ITER project and fusion reactor, understanding and development of plasma controllability in ITER and DEMO relevant higher beta regimes are essential. JT-60SA has focused the program on the plasma controllability for scenario development and risk mitigation in ITER as well as on investigating DEMO relevant regimes. This paper summarizes the high research priorities and strategy for the JT-60SA project. Recent works on simulation studies to prepare the plasma physics and control experiments are presented, such as plasma breakdown and equilibrium controls, hybrid and steady-state scenario development, and risk mitigation techniques. Contributions of JT-60SA to ITER and DEMO have been clarified through those studies.Peer reviewe

Measuring communication as a core outcome in aphasia trials: Results of the ROMA-2 international core outcome set development meeting

BACKGROUND: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia-ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. AIM: To establish consensus on a communication OMI for inclusion in the ROMA COS. METHODS & PROCEDURES: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by ≥ 70% of participants. OUTCOMES & RESULTS: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living-3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. CONCLUSIONS & IMPLICATIONS: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research. WHAT THIS PAPER ADDS: What is already known on this subject International consensus has been reached on five core constructs to be routinely measured in aphasia treatment studies. International consensus has also been established for OMIs for the three constructs of language, quality of life and emotional well-being. Before this study, OMIs for the constructs of communication and patient-reported satisfaction/impact of treatment were not established. What this paper adds to existing knowledge We gained international consensus on an OMI for the construct of communication. TST is recommended for inclusion in the ROMA COS for routine use in aphasia treatment research. What are the potential or actual clinical implications of this work? The ROMA COS recommends OMIs for a minimum set of outcomes for adults with post-stroke aphasia within phases I-IV aphasia treatment research. Although not intended for clinical use, clinicians may employ the instruments of the ROMA COS, considering the quality of their measurement properties. The systematic inclusion of a measure of communication, such as TST, in clinical practice could ultimately support the implementation of research evidence and best practices

Collaborative turn-construction practices of people with primary progressive aphasia and their family conversation partners

BACKGROUND: Primary progressive aphasia describes a group of three rare language-led dementias: semantic, logopenic, and non-fluent. The small number of conversation analysis studies to date suggest that repair and turn-construction practices in primary progressive aphasia are similar to those seen in post-stroke aphasia. This study investigates the collaborative aspect of these practices between people with primary progressive aphasia and their conversation partners. METHHOD: Conversation analysis was used to investigate collaboration in repair and turn-construction practices in 10-minute video recordings of natural conversation collected from two dyads, one with logopenic and one with mixed primary progressive aphasia. RESULTS: This study demonstrates that people with primary progressive aphasia have a range of practices available to construct their turns, and that their conversation partners collaborate to co-construct talk. DISCUSSION: Findings demonstrate that collaboration can support interaction or lead to further interactional trouble. Collaborative practices are important targets for speech and language therapy interventions

Results from a randomised controlled pilot study of the Better Conversations with Primary Progressive Aphasia (BCPPA) communication partner training program for people with PPA and their communication partners

Abstract Background There has been a growing focus on functional communication interventions for primary progressive aphasia (PPA). These interventions aim to support individuals to participate in life situations. One such intervention, communication partner training (CPT) aims to change conversation behaviours in both the person with PPA and their communication partner (CP). CPT has a growing evidence base in stroke aphasia; however, these programmes are not designed to meet the needs of people with progressive communication difficulties. To address this, the authors developed a CPT program entitled Better Conversations with PPA (BCPPA) and undertook a pilot trial to establish for a future full trial; predicted recruitment rates, acceptability, an assessment of treatment fidelity and an appropriate primary outcome measure. Methodology This was a single-blind, randomised controlled pilot study comparing BCPPA to no treatment, delivered across 11 National Health Service Trusts in the UK. A random sample of eight recordings of local collaborators delivering the intervention were analysed to examine fidelity. Participants completed feedback forms reporting on acceptability. Pre- and post-intervention measures targeted conversation behaviours, communication goals and quality of life. Results Eighteen people with PPA and their CPs (9 randomised to BCPPA, 9 randomised to no treatment) completed the study. Participants in the intervention group rated BCPPA positively. Treatment fidelity was 87.2%. Twenty-nine of 30 intervention goals were achieved or over-achieved and 16 of 30 coded conversation behaviours demonstrated change in the intended direction. The Aphasia Impact Questionnaire was identified as the preferred outcome measure. Conclusion The first randomised controlled UK pilot study of a CPT program for people with PPA and their families demonstrates BCPPA is a promising intervention. The intervention was acceptable, treatment fidelity high and an appropriate measure identified. Results of this study indicate a future RCT of BCPPA is feasible. Trial registration Registered 28/02/2018 ISRCTN10148247

VOICE: A communication skills training intervention using conversation analysis and simulated interaction

This manual describes the process of developing simulation training to be used in a communication skills training course. The underpinning principle is the use of conversation analysis to enhance simulated interactions. The training uses scenarios based on video data of actual interactions along with transcripts that have been closely examined. The aim is to create authentic experiential learning opportunities for people who want to improve their communication skills

Metastatic colorectal cancer in young adults: a study from the South Australian Population-Based Registry

Abstract not availableSina Vatandoust, Timothy J. Price, Shahid Ullah, Amitesh C. Roy, Carole Beeke, Joanne P. Young, Amanda Townsend, Robert Padbury, David Roder, Christos S. Karapeti

Impact of age on choice of chemotherapy and outcome in advanced colorectal cancer

BackgroundAge is a major risk factor for development of sporadic colorectal cancer but elderly patients are underrepresented in clinical trials and are potentially offered chemotherapy less often.MethodsData were obtained from South Australian Clinical Registry for advanced colorectal cancer between 1st February 2006 and 9th September 2010. Patients who received chemotherapy were analysed to assess the impact of single versus combination chemotherapy and to assess the outcome in two age cohorts, age ResultsOut of a total of 1745 patients in the database during this time period, 951 (54.5%) received systemic chemotherapy. 286 (30%) received first line therapy (median age 74 years) with single agent fluoropyrimidine and 643 patients (68%) received first line combination chemotherapy (median age 64 years). The median overall survival of patients receiving first line combination chemotherapy was 23.9 months compared to 17.2 months for those who received single agent fluoropyrimidine (pConclusionTreatment outcomes are comparable in both the elderly and younger patients. Patients who received initial combination chemotherapy were younger and had a longer median overall survival. In our study, age appeared to influence the treatment choices but not necessarily outcome.Muhammad A. Khattak, Amanda R. Townsend, Carol Beeke, Christos S. Karapetis, Colin Luke, Rob Padbury, Guy Maddern, David Roder and Timothy J. Pric

Does the Primary Site of Colorectal Cancer Impact Outcomes for Patients With Metastatic Disease?

Presented in part at the ASCO Gastrointestinal Symposium, January 15-17, 2014, and the American Society of Clinical Oncology, May 30 to June 3, 2014.Abstract not availableTimothy J. Price, Carol Beeke, Shahid Ullah, Robert Padbury, Guy Maddern, David Roder, Amanda R. Townsend, James Moore, Amitesh Roy, Yoko Tomita and Christos Karapeti