The St Andrews Institute for Clinical Research: An early Experiment in Collaboration

Sir James Mackenzie is revered by general practitioners as the father of general practice-based research.' His name is associated with the University Department of General Practice at Edinburgh and with the Chair at Aberdeen, and he is commemorated in the James Mackenzie lecture given annually at the Royal College of General Practitioners. His fame rests largely on his achievements as a solitary researcher while he worked as a GP in Burnley, a mill town in Lancashire, between 1879 and 1907. It was here that he carried out the pioneering work which contributed to the development of the "new cardiology" at the beginning of the century.2 His work in Burnley took him away from general practice and he moved to London to take up private and hospital consulting work to further the impact of his research. He regarded himself, however, as first and foremost a GP, and believed general practice was the proper place for clinical research.3 Mackenzie was so committed to this belief that he left London in 1919, an ill man at the age of sixty-six, and the GPs of St Andrews working together in collaborative research under Mackenzie's leadership. This paper will reassess Mackenzie's significance for the development of general practice-based research and for general practice as a specialty by examining this project of his later years. The Institute was an innovative venture at this time. Clinical research was still very much an individualistic activity and, as fewer GPs were doing research in the form of MD degrees, individual GPs were generally less likely to be involved in research.4 The St Andrews Institute can be seen as an attempt by Mackenzie to set up the kind of research structure for GPs that was beginning to emerge in the London teaching hospitals: specialist clinicians associated with university scientists. Mackenzie's model did not continue and there was a long gap before university departments of general practice emerged (the first professor of general practice was Richard Scott appointed in 1963 in Edinburgh).' The first section of the paper will fill in some background of Mackenzie's life and work before he came to St Andrews in order to give some understanding of his motivation and experience, and of his early fame. The second section will describe the Institute, its members, what it set out to do, and, particularly, how it was funded; and the final section will discuss why Mackenzie did not succeed in establishing the Institute on a permanent basis and assess its significance in the history of GP research

The dangerous practice of empathy

Chronic pain affects more persons than cancer and heart disease. Chronic pain increases the risk for depression and decreased coping, especially in the elderly, further increasing the cost of care. The psychological and emotional components of chronic pain are often not addressed in the treatment plan. An overview of chronic pain and literature to support the use of music to decrease the perception of pain in community-dwelling adults with chronic osteoarthritis pain and in hospitalized adults who have higher levels of acute pain after hip and knee surgery due to long periods of chronic pain preceding surgery is presented. The results of several randomized controlled trials are reviewed in depth. Results from these studies demonstrate decreased pain, improved ability to ambulate after surgery and fewer episodes of post-operative acute confusion in older adults who listened to music compared with those who did not. Music, therefore, has the ability to reduce chronic pain in older adults with osteoarthritis. Selecting appropriate music for listening should be based on patient preference. Music is a safe, non-invasive, inexpensive and easy-to-use intervention that should be added to the treatment plan for older adults with chronic pain. (PsycINFO Database Record (c) 2016 APA, all rights reserved

"I feel so stupid because I can't give a proper answer ..." How older adults describe chronic pain: a qualitative study

Background - Over 50% of older adults experience chronic pain. Poorly managed pain threatens independent functioning, limits social activities and detrimentally affects emotional wellbeing. Yet, chronic pain is not fully understood from older adults’ perspectives; subsequently, pain management in later life is not necessarily based on their priorities or needs. This paper reports a qualitative exploration of older adults’ accounts of living with chronic pain, focusing on how they describe pain, with a view to informing approaches to its assessment. Methods - Cognitively intact men and women aged over sixty-five who lived in the community opted into the study through responding to advertisements in the media and via contacts with groups and organisations in North-East Scotland. Interviews were transcribed and thematically analysed using a framework approach. Results - Qualitative individual interviews and one group interview were undertaken with 23 older adults. Following analysis, the following main themes emerged: diversity in conceptualising pain using a simple numerical score; personalising the meaning of pain by way of stories, similes and metaphors; and, contextualising pain in relation to its impact on activities. Conclusions - The importance of attending to individuals’ stories as a meaningful way of describing pain for older adults is highlighted, suggesting that a narrative approach, as recommended and researched in other areas of medicine, may usefully be applied in pain assessment for older adults. Along with the judicious use of numerical tools, this requires innovative methods to elicit verbal accounts, such as using similes and metaphors to help older adults describe and discuss their experience, and contextualising the effects of pain on activities that are important to them

Gut Feelings as a Third Track in General Practitioners’ Diagnostic Reasoning

BACKGROUND: General practitioners (GPs) are often faced with complicated, vague problems in situations of uncertainty that they have to solve at short notice. In such situations, gut feelings seem to play a substantial role in their diagnostic process. Qualitative research distinguished a sense of alarm and a sense of reassurance. However, not every GP trusted their gut feelings, since a scientific explanation is lacking. OBJECTIVE: This paper explains how gut feelings arise and function in GPs' diagnostic reasoning. APPROACH: The paper reviews literature from medical, psychological and neuroscientific perspectives. CONCLUSIONS: Gut feelings in general practice are based on the interaction between patient information and a GP's knowledge and experience. This is visualized in a knowledge-based model of GPs' diagnostic reasoning emphasizing that this complex task combines analytical and non-analytical cognitive processes. The model integrates the two well-known diagnostic reasoning tracks of medical decision-making and medical problem-solving, and adds gut feelings as a third track. Analytical and non-analytical diagnostic reasoning interacts continuously, and GPs use elements of all three tracks, depending on the task and the situation. In this dual process theory, gut feelings emerge as a consequence of non-analytical processing of the available information and knowledge, either reassuring GPs or alerting them that something is wrong and action is required. The role of affect as a heuristic within the physician's knowledge network explains how gut feelings may help GPs to navigate in a mostly efficient way in the often complex and uncertain diagnostic situations of general practice. Emotion research and neuroscientific data support the unmistakable role of affect in the process of making decisions and explain the bodily sensation of gut feelings.The implications for health care practice and medical education are discussed

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C