Analysis of glottal source parameters in Parkinsonian speech

Diagnosis and monitoring of Parkinson\u27s disease has a number of challenges as there is no definitive biomarker despite the broad range of symptoms. Research is ongoing to produce objective measures that can either diagnose Parkinson\u27s or act as an objective decision support tool. Recent research on speech based measures have demonstrated promising results. This study aims to investigate the characteristics of the glottal source signal in Parkinsonian speech. An experiment is conducted in which a selection of glottal parameters are tested for their ability to discriminate between healthy and Parkinsonian speech. Results for each glottal parameter are presented for a database of 50 healthy speakers and a database of 16 speakers with Parkinsonian speech symptoms. Receiver operating characteristic (ROC) curves were employed to analyse the results and the area under the ROC curve (AUC) values were used to quantify the performance of each glottal parameter. The results indicate that glottal parameters can be used to discriminate between healthy and Parkinsonian speech, although results varied for each parameter tested. For the task of separating healthy and Parkinsonian speech, 2 out of the 7 glottal parameters tested produced AUC values of over 0.9

What is different about living alone with cancer in older age? A qualitative study of experiences and preferences for care

Background: Increasing numbers of older patients with advanced cancer live alone but there is little research on how well health services meet their needs. The aim of this study was to compare the experiences and future preferences for care between two groups of older people with cancer in their last year of life; those who live alone, and those who live with co-resident carers. Methods: In-depth qualitative interviews were conducted with 32 people aged between 70 and 95 years who were living with cancer. They were recruited from general practices and hospice day care, when the responsible health professional answered no to the question, of whether they would be surprised if the patient died within twelve months. Twenty participants lived alone. Interviews were recorded and transcribed and the data analysed using a Framework approach, focussing on the differences and commonalities between the two groups. Results: Many experiences were common to all participants, but had broader consequences for people who lived alone. Five themes are presented from the data: a perception that it is a disadvantage to live alone as a patient, the importance of relational continuity with health professionals, informal appraisal of care, place of care and future plans. People who lived alone perceived emotional and practical barriers to accessing care, and many shared an anxiety that they would have to move into a care home. Participants were concerned with remaining life, and all who lived alone had made plans for death but not for dying. Uncertainty of timescales and a desire to wait until they knew that death was imminent were some of the reasons given for not planning for future care needs. Conclusions: Older people who live alone with cancer have emotional and practical concerns that are overlooked by their professional carers. Discussion and planning for the future, along with continuity in primary care may hold the key to enhancing end-of-life care for this group of patients

A comparison of strategies to recruit older patients and carers to end-of-life research in primary care

Background Older adults receive most of their end-of-life care in the community, but there are few published data to guide researchers on recruitment to studies in primary care. The aim of this study was to compare recruitment of patients and bereaved carers from general practices in areas with different research network support, and identify challenges in obtaining samples representative of those in need of end-of-life care. Methods Comparative analysis of recruitment from general practices to two face-to-face interview studies concerned with 1) carers’ perceptions of transitions between settings for decedents aged over 75 years and 2) the experiences of older patients living with cancer at the end-of-life. Results 33 (15% of invitees) patients and 118 (25%) carers were interviewed. Carers from disadvantaged areas were under-represented. Recruitment was higher when researchers, rather than research network staff, were in direct contact with general practices. Most practices recruited no more than one carer, despite a seven fold difference in the number of registered patients. The proportion identified as eligible for patient interviews varied by a factor of 38 between practices. Forty-four Primary Care Trusts granted approval to interview carers; two refused. One gave no reason; a second did not believe that general practitioners would be able to identify carers. Conclusion Obtaining a representative sample of patients or carers in end-of-life research is a resource intensive challenge. Review of the regulatory and organisational barriers to end-of-life researchers in primary care is required. Research support networks provide invaluable assistance, but researchers should ensure that they are alert to the ways in which they may influence study recruitment

Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population

Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. METHODS Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes. RESULTS 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations. CONCLUSION Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma

Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population.

Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. METHODS: Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes. RESULTS: 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations. CONCLUSION: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease