Assessing uncertainties in scattering correction algorithms for reflective tube absorption measurements made with a WET Labs ac-9

In situ absorption measurements collected with a WET Labs ac-9 employing a reflective tube approach were scatter corrected using several possible methods and compared to reference measurements made by a PSICAM to assess performance. Overall, two correction methods performed best for the stations sampled: one using an empirical relationship between the ac-9 and PSICAM to derive the scattering error (ε) in the nearinfrared (NIR), and one where ε was independently derived from concurrent measurements of the volume scattering function (VSF). Application of the VSF-based method may be more universally applicable, although difficult to routinely apply because of the lack of commercially available VSF instrumentation. The performance of the empirical approach is encouraging as it relies only on the ac meter measurement and may be readily applied to historical data, although there are inevitably some inherent assumptions about particle composition that hinder universal applicability. For even the best performing methods, residual errors of 20% or more were commonly observed for many water types. For clear ocean waters, a conventional baseline subtraction with the assumption of negligible near-IR absorption performed as well or better than the above methods because propagated uncertainties were lower than observed with the proportional method

Cardiovascular disease in Alpha 1 antitrypsin deficiency:an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools

Background: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. Results: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. Conclusion: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD

Artificial intelligence technologies and compassion in healthcare: A systematic scoping review

BackgroundAdvances in artificial intelligence (AI) technologies, together with the availability of big data in society, creates uncertainties about how these developments will affect healthcare systems worldwide. Compassion is essential for high-quality healthcare and research shows how prosocial caring behaviors benefit human health and societies. However, the possible association between AI technologies and compassion is under conceptualized and underexplored.ObjectivesThe aim of this scoping review is to provide a comprehensive depth and a balanced perspective of the emerging topic of AI technologies and compassion, to inform future research and practice. The review questions were: How is compassion discussed in relation to AI technologies in healthcare? How are AI technologies being used to enhance compassion in healthcare? What are the gaps in current knowledge and unexplored potential? What are the key areas where AI technologies could support compassion in healthcare?Materials and methodsA systematic scoping review following five steps of Joanna Briggs Institute methodology. Presentation of the scoping review conforms with PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews). Eligibility criteria were defined according to 3 concept constructs (AI technologies, compassion, healthcare) developed from the literature and informed by medical subject headings (MeSH) and key words for the electronic searches. Sources of evidence were Web of Science and PubMed databases, articles published in English language 2011–2022. Articles were screened by title/abstract using inclusion/exclusion criteria. Data extracted (author, date of publication, type of article, aim/context of healthcare, key relevant findings, country) was charted using data tables. Thematic analysis used an inductive-deductive approach to generate code categories from the review questions and the data. A multidisciplinary team assessed themes for resonance and relevance to research and practice.ResultsSearches identified 3,124 articles. A total of 197 were included after screening. The number of articles has increased over 10 years (2011, n = 1 to 2021, n = 47 and from Jan–Aug 2022 n = 35 articles). Overarching themes related to the review questions were: (1) Developments and debates (7 themes) Concerns about AI ethics, healthcare jobs, and loss of empathy; Human-centered design of AI technologies for healthcare; Optimistic speculation AI technologies will address care gaps; Interrogation of what it means to be human and to care; Recognition of future potential for patient monitoring, virtual proximity, and access to healthcare; Calls for curricula development and healthcare professional education; Implementation of AI applications to enhance health and wellbeing of the healthcare workforce. (2) How AI technologies enhance compassion (10 themes) Empathetic awareness; Empathetic response and relational behavior; Communication skills; Health coaching; Therapeutic interventions; Moral development learning; Clinical knowledge and clinical assessment; Healthcare quality assessment; Therapeutic bond and therapeutic alliance; Providing health information and advice. (3) Gaps in knowledge (4 themes) Educational effectiveness of AI-assisted learning; Patient diversity and AI technologies; Implementation of AI technologies in education and practice settings; Safety and clinical effectiveness of AI technologies. (4) Key areas for development (3 themes) Enriching education, learning and clinical practice; Extending healing spaces; Enhancing healing relationships.ConclusionThere is an association between AI technologies and compassion in healthcare and interest in this association has grown internationally over the last decade. In a range of healthcare contexts, AI technologies are being used to enhance empathetic awareness; empathetic response and relational behavior; communication skills; health coaching; therapeutic interventions; moral development learning; clinical knowledge and clinical assessment; healthcare quality assessment; therapeutic bond and therapeutic alliance; and to provide health information and advice. The findings inform a reconceptualization of compassion as a human-AI system of intelligent caring comprising six elements: (1) Awareness of suffering (e.g., pain, distress, risk, disadvantage); (2) Understanding the suffering (significance, context, rights, responsibilities etc.); (3) Connecting with the suffering (e.g., verbal, physical, signs and symbols); (4) Making a judgment about the suffering (the need to act); (5) Responding with an intention to alleviate the suffering; (6) Attention to the effect and outcomes of the response. These elements can operate at an individual (human or machine) and collective systems level (healthcare organizations or systems) as a cyclical system to alleviate different types of suffering. New and novel approaches to human-AI intelligent caring could enrich education, learning, and clinical practice; extend healing spaces; and enhance healing relationships.ImplicationsIn a complex adaptive system such as healthcare, human-AI intelligent caring will need to be implemented, not as an ideology, but through strategic choices, incentives, regulation, professional education, and training, as well as through joined up thinking about human-AI intelligent caring. Research funders can encourage research and development into the topic of AI technologies and compassion as a system of human-AI intelligent caring. Educators, technologists, and health professionals can inform themselves about the system of human-AI intelligent caring

Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein

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.Abstract Background Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown. Results We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner. Conclusion It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.Published versio

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

BACKGROUND: Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS: In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS: From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION: In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING: National Institute for Health Research

How to tie dangerous surgical knots: easily. Can we avoid this?

ObjectiveSecure knots are essential in all areas of surgical, medical and veterinary practice. Our hypothesis was that technique of formation of each layer of a surgical knot was important to its security.DesignEqual numbers of knots were tied, by each of three groups, using three techniques, for each of four suture materials; a standard flat reef knot (FRK), knots tied under tension (TK) and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and tested by distraction with increasing force, till each material broke or the knot separated completely.SettingTemporary knot tying laboratory.MaterialsThe suture materials were, 2/0 polyglactin 910 (Vicryl), 3/0 polydioxanone, 4/0 poliglecaprone 25 (Monocryl) and 1 nylon (Ethilon).ParticipantsThree groups comprised, a senior surgeon, a resident surgeon and three medical students.Outcome measuresProportion of each knot type that slipped, degree of slippage and length of suture held in loop secured by each knot type.Results20% of FRK tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip was significantly less for FRK (mean 6.3%–, 95% CI 2.2% to 10.4%) than for TK (mean 312%, 95% CI 280.0% to 344.0%) and NHCK (mean 113.0%, –95% CI 94.3% to 131.0%).The mean length of suture in loops held within (FRK mean 25.1 mm 95% CI 24.2 to 26.0 mm) was significantly greater than mean lengths held by the other techniques (TK mean 17.0 mm, 95% CI 16.3 to 17.7 mm), (NHCK mean 16.3 mm, 95% CI 15.9 to 16.7 mm). The latter two types of knot may have tightened more than anticipated, in comparison to FRK, with potential undue tissue tension.ConclusionMeticulous technique of knot tying is essential for secure knots, appropriate tissue tension and the security of anastomoses and haemostasis effected.</jats:sec