NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma

Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is not typical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been poorly studied in patients with B-CLL/SLL. Here we report for the first time the NK cell phenotype and function in patients with B-CLL and SLL alongside their transcriptional profile. We show for the first time impaired B-CLL NK cell function in a xenograft model with reduced activating receptor expression including NKG2D, DNAM-1 and NCRs in-vitro. Importantly, we show these functional differences are associated with transcriptional downregulation of cytotoxic pathway genes, including activating receptors, adhesion molecules, cytotoxic molecules and intracellular signalling molecules, which remain intact in patients with SLL. In conclusion, NK cell function is markedly influenced by the anatomical site of the tumor in patients with B-CLL/SLL and lymphocytosis leads to marked impairment of NK cell activity. These observations have implications for treatment protocols which seek to preserve immune function by limiting the exposure of NK cells to tumor cells within the peripheral circulation

'Sifting the significance from the data' - the impact of high-throughput genomic technologies on human genetics and health care.

This report is of a round-table discussion held in Cardiff in September 2009 for Cesagen, a research centre within the Genomics Network of the UK's Economic and Social Research Council. The meeting was arranged to explore ideas as to the likely future course of human genomics. The achievements of genomics research were reviewed, and the likely constraints on the pace of future progress were explored. New knowledge is transforming biology and our understanding of evolution and human disease. The difficulties we face now concern the interpretation rather than the generation of new sequence data. Our understanding of gene-environment interaction is held back by our current primitive tools for measuring environmental factors, and in addition, there may be fundamental constraints on what can be known about these complex interactions.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Taking the steps toward sustainable livestock: our multidisciplinary global farm platform journey

International audienc

A multi-centre, randomised controlled trial of cognitive therapy to prevent harmful compliance with command hallucinations

<p>Abstract</p> <p>Background</p> <p>Command hallucinations are among the most distressing, high risk and treatment resistant symptoms for people with psychosis; however, currently, there are no evidence-based treatment options available for this group. A cognitive therapy grounded in the principles of the Social Rank Theory, is being evaluated in terms of its effectiveness in reducing harmful compliance with command hallucinations.</p> <p>Methods/Design</p> <p>This is a single blind, intention-to-treat, multi-centre, randomized controlled trial comparing Cognitive Therapy for Command Hallucinations + Treatment as Usual with Treatment as Usual alone. Eligible participants have to fulfil the following inclusion criteria: i) ≥16 years; ii) ICD-10 diagnosis of schizophrenia or related disorder; iii) command hallucinations for at least 6 months leading to risk of harm to self or others. Following the completion of baseline assessments, eligible participants will be randomly allocated to either the Cognitive Therapy for Command Hallucinations + Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at 9 and 18 months post randomization with assessors blind to treatment allocation. The primary outcome is compliance behaviour and secondary outcomes include beliefs about voices' power, distress, psychotic symptoms together with a health economic evaluation. Qualitative interviews with services users will explore the acceptability of Cognitive Therapy for Command Hallucinations.</p> <p>Discussion</p> <p>Cognitive behaviour therapy is recommended for people with psychosis; however, its focus and evaluation has primarily revolved around the reduction of psychotic symptoms. In this trial, however, the focus of the cognitive behavioural intervention is on individuals' appraisals, behaviour and affect and not necessarily symptoms; this is also reflected in the outcome measures used. If successful, the results will mark a significant breakthrough in the evidence base for service users and clinicians and will provide a treatment option for this group where none currently exist. The trial will open the way for further breakthrough work with the 'high risk' population of individuals with psychosis, which we would intend to pursue.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN62304114">ISRCTN62304114</a></p

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure : An Exploratory Proof-of-Concept Trial

Acknowledgments We would like to extend our sincerest gratitude to all the colleagues and hospital staff who worked tirelessly throughout the pandemic and without whom this work would not have been possible. Firstly, we would like to thank our colleagues in the intensive care unit (ICU), in particular the matrons, Sean Carroll and Sinead Hanton, and research nurses, Filipe Helder and Amitaa Maharajh for their support, and bedside nurses who bore the responsibility of drug administration. We would also like to extend our thanks to ICU consultants who acted as professional legal consultees on behalf of critical care patients. Equally, we would like to thank colleagues within the respiratory team. Their expertise was instrumental to our role in treating patients on 8N and 8E wards. A special mention to lead Nurse Mary Emerson; we were grateful for her knowledge, support and for facilitating the training for the nebulizer and drug administration on the wards. We would like to thank Aarti Nandani and all the staff in the Royal Free clinical trials pharmacy for their immense support throughout the whole pandemic, especially considering their ever-increasing workload at the time. Thanks also to the HSL coagulation laboratory, the Trust R&D department and all the staff working to cover during a very challenging time. We are also very grateful to the Royal Free charity for funding this study. Finally, we would like to thank all the clinical nurses, physiotherapists, research data managers and healthcare professionals within the Haemophilia department (and wider hospital) for all their many efforts in supporting this study. This trial was overseen by an independent data monitoring committee, chaired by Najib Rahman, Director of the Oxford Respiratory Trials Unit, University of Oxford and comprises the following committee members: Mike Makris, Jonathan Silversides and Henry Watson. Funding Royal Free Charity Trust Fund 35 provided funding for this study. The study drug was provided by Boehringer Ingelheim (BI). BI had no role in the design, analysis, or interpretation of the results. They were given the opportunity to review the manuscript for medical and scientific accuracy since it relates to BI substances and intellectual property considerations.Peer reviewedPublisher PD

The predictive role of symptoms in COVID-19 diagnostic models : A longitudinal insight

Acknowledgements 2019nCoV-302 Study Group Members: The NVX-CoV2373-2019nCoV-302 clinical trial was a collective group effort across multiple institutions and locations. Below is a list of sites and staff that significantly contributed to the implementation and conduct of the NVX-CoV2373-2019nCoV-302 clinical trial.Peer reviewe

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of NovavaxPeer reviewedPublisher PD

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD