THU0334 LASER SPECKLE CONTRAST ANALYSIS FOR MEASUREMENT OF PERIPHERAL BLOOD PERFUSION IN SYSTEMIC SCLEROSIS PATIENTS: CAN IT PREDICT FUTURE ISCHEMIC DIGITAL TROPHIC LESIONS?

Background:Vasculopathy is a hallmark of systemic sclerosis (SSc). Laser speckle contrast analysis (LASCA) is a research tool to assess peripheral blood perfusion (PBP) (1). At this moment, its reliability has been attested in SSc patients, but its predictive value for future ischemic digital trophic lesions (DTL) is unknown (1).Objectives:To investigate in an unselected, prospective SSc cohort if baseline LASCA PBP measurements can discriminate between patients who will develop ischemic DTL (iDTL) and those who will not.Methods:Patients (fulfilling 2013 ACR/EULAR criteria and/or 2001 LeRoy and Medsger criteria) were recruited during the period of December 2017 to September 2018. LASCA was performed at baseline, in standardized conditions (1). Regions of interest (ROIs) (diameter 1 cm) were outlined at the 2nd-5thfingertip both volar and dorsal. The 'average PBP' of these ROIs was calculated (expressed in arbitrary perfusion units [PU]). A monthly telephone survey was conducted for 1 year to investigate DTL occurrence. DTL were considered 'ischemic' if not related to calcinosis. Logistic regression and ROC analysis were used to assess if average PBP is predictive of future iDTL.Results:Of the 106 patients with complete follow-up (92 women [86,8%]; 18 limited SSc [17,0%], 82 limited cutaneous SSc [77,4%], 6 diffuse cutaneous SSc [5,7%]), 29 patients (27,4%) had a DTL history. Forty-nine patients (46,2%) were on vasodilator therapy. Only 7 patients developed at least 1 iDTL during follow-up (6,6%) (Figure 1a). Performing univariate logistic regression (ULR), average PBP was not predictive for future iDTL (Table 1). Of note, analyzing only the patients not taking vasodilators, average PBP in the 'iDTL group' (n = 3) was median 46,8 PU (min. 45,6 - max. 68,8) vs. median 141,4 PU (min. 24,4 - max. 269,5) in the 'no iDTL group' (n = 54) (Figure 1b). In this subgroup, all 3 patients who developed iDTL (100%) had an average PBP ≤ 70 PU whereas only 9 of the 54 patients without iDTL development (16,7%) had such PBP values.Table 1.Results of ULRSummary statisticsULRVariableiDTL cases(n = 7)Non-iDTL cases(n = 99)ParameterOR(95% CI)pROC AUC(95% CI)Average PBP (PU) mean (+/- SD)123,0 (74,6)142,9 (61,9)Average PBP (linear)0,995(0,982-1,007)0,4180,597(0,352-0,843)Conclusion:In this pilot study with an unselected day-to-day SSc population, where patients were allowed to continue vasodilators, there was an unexpected low iDTL incidence, undermining the power of our study. Even though, the observations in the subgroup of patients not taking vasodilators deserve future investigation to assess whether low PBP values, as measured by LASCA, are associated with a higher iDTL incidence.References:[1]Cutolo M, Vanhaecke A, et al. Autoimmun Rev. 2018;17(8):775-80.Figure 1.Distribution of 'average PBP' as measured by LASCA for 'no iDTL group' and 'iDTL group'Disclosure of Interests:Claire Debusschere: None declared, Amber Vanhaecke: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Ellen Deschepper: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Spr

Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone

Background: We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrYC57) was substituted for that of A/J mice (ChrYA), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrYA strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, cardiomyocytes from the resulting A/J-chrYC57 strain were larger than in their A/J counterparts. We further used these strains to test whether: 1) the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2) post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrYC57 and chrYA. Results: The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6JchrYA resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrYA to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrYA hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1) p53 signaling, which comprises the interacting genes Ccnd1, Pten and Cdkn1a that are also potential coregulators of the androgen receptors, and 2) circadian rhythm, which comprises Arntl/Bmal1, which may in turn regulate cell growth via the control of Cdkn1a. Conclusion: Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from their C57BL/6J-chrYA counterparts, it affected gene expression in the hearts from both strains. However, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective manner, which provides possible mechanisms explaining how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice.Bastien Llamas, Ricardo A Verdugo, Gary A Churchill and Christian F Descheppe

Exploring wind direction and SO2 concentration by circular-linear density estimation

The study of environmental problems usually requires the description of variables with different nature and the assessment of relations between them. In this work, an algorithm for flexible estimation of the joint density for a circular-linear variable is proposed. The method is applied for exploring the relation between wind direction and SO2 concentration in a monitoring station close to a power plant located in Galicia (NW-Spain), in order to compare the effectiveness of precautionary measures for pollutants reduction in two different years.Comment: 17 pages, 7 figures, 2 table

Astrocyte-Derived Thrombospondin Induces Cortical Synaptogenesis in a Sex-Specific Manner

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the CNS. Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared with female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to TSP2, which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17b -estradiol (E2) production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that male and female neurons show a divergent response to TSP synaptogenic signaling, contributing to sex differences in astrocyte-mediated synaptic connectivity

Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial

Copyright @ Queen’s Printer and Controller of HMSO 2012. This work was produced by Sharples et al. under the terms of a commissioning contract issued by the Secretary of State for Health.Objective: To assess the clinical effectiveness and cost-effectiveness of endosonography (followed by surgical staging if endosonography was negative), compared with standard surgical staging alone, in patients with non-small cell lung cancer (NSCLC) who are otherwise candidates for surgery with curative intent. Design: A prospective, international, open-label, randomised controlled study, with a trialbased economic analysis. Setting: Four centres: Ghent University Hospital, Belgium; Leuven University Hospitals,Belgium; Leiden University Medical Centre, the Netherlands; and Papworth Hospital, UK. Participants: Inclusion criteria: known/suspected NSCLC, with suspected mediastinal lymph node involvement; otherwise eligible for surgery with curative intent; clinically fit for endosonography and surgery; and no evidence of metastatic disease. Exclusion criteria: previous lung cancer treatment; concurrent malignancy; uncorrected coagulopathy; and not suitable for surgical staging. Interventions: Study patients were randomised to either surgical staging alone (n = 118) or endosonography followed by surgical staging if endosonography was negative (n = 123). Endosonography diagnostic strategy used endoscopic ultrasound-guided fine-needle aspiration combined with endobronchial ultrasound-guided transbronchial needle aspiration, followed by surgical staging if these tests were negative. Patients with no evidence of mediastinal metastases or tumour invasion were referred for surgery with curative intent. If evidence of malignancy was found, patients were referred for chemoradiotherapy. Main outcome measures: The main clinical outcomes were sensitivity (positive diagnostic test/nodal involvement during any diagnostic test or thoracotomy) and negative predictive value (NPV) of each diagnostic strategy for the detection of N2/N3 metastases, unnecessary thoracotomy and complication rates. The primary economic outcome was cost–utility of the endosonography strategy compared with surgical staging alone, up to 6 months after randomisation, from a UK NHS perspective. Results: Clinical and resource-use data were available for all 241 patients, and complete utilities were available for 144. Sensitivity for detecting N2/N3 metastases was 79% [41/52; 95% confidence interval (CI) 66% to 88%] for the surgical arm compared with 94% (62/66; 95% CI 85% to 98%) for the endosonography strategy (p = 0.02). Corresponding NPVs were 86% (66/77; 95% CI 76% to 92%) and 93% (57/61; 95% CI 84% to 97%; p = 0.26). There were 21/118 (18%) unnecessary thoracotomies in the surgical arm compared with 9/123 (7%) in the endosonography arm (p = 0.02). Complications occurred in 7/118 (6%) in the surgical arm and 6/123 (5%) in the endosonography arm (p = 0.78): one pneumothorax related to endosonography and 12 complications related to surgical staging. Patients in the endosonography arm had greater EQ-5D (European Quality of Life-5 Dimensions) utility at the end of staging (0.117; 95% CI 0.042 to 0.192; p = 0.003). There were no other significant differences in utility. The main difference in resource use was the number of thoracotomies: 66% patients in the surgical arm compared with 53% in the endosonography arm. Resource use was similar between the groups in all other items. The 6-month cost of the endosonography strategy was £9713 (95% CI £7209 to £13,307) per patient versus £10,459 (£7732 to £13,890) for the surgical arm, mean difference £746 (95% CI –£756 to £2494). The mean difference in quality-adjusted life-year was 0.015 (95% CI –0.023 to 0.052) in favour of endosonography, so this strategy was cheaper and more effective. Conclusions: Endosonography (followed by surgical staging if negative) had higher sensitivity and NPVs, resulted in fewer unnecessary thoracotomies and better quality of life during staging, and was slightly more effective and less expensive than surgical staging alone. Future work could investigate the need for confirmatory mediastinoscopy following negative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the diagnostic accuracy of EUS-FNA or EBUS-TBNA separately and the delivery of both EUSFNA or EBUS-TBNA by suitably trained chest physicians.This project was funded by the NIHR Health Technology Assessment programm

Prevalence of skin pressure injury in critical care patients in the UK: results of a single-day point prevalence evaluation in adult critically ill patients.

OBJECTIVES: Hospital-acquired pressure injuries (PIs) are a source of morbidity and mortality, and many are potentially preventable. DESIGN: This study prospectively evaluated the prevalence and the associated factors of PIs in adult critical care patients admitted to intensive care units (ICU) in the UK. SETTING: This service evaluation was part of a larger, international, single-day point prevalence study of PIs in adult ICU patients. Training was provided to healthcare givers using an electronic platform to ensure standardised recognition and staging of PIs across all sites. PARTICIPANTS: The characteristics of the ICUs were recorded before the survey; deidentified patient data were collected using a case report form and uploaded onto a secure online platform. PRIMARY AND SECONDARY OUTCOME MEASURES: Factors associated with ICU-acquired PIs in the UK were analysed descriptively and using mixed multiple logistic regression analysis. RESULTS: Data from 1312 adult patients admitted to 94 UK ICUs were collected. The proportion of individuals with at least one PI was 16% (211 out of 1312 patients), of whom 8.8% (n=115/1312) acquired one or more PIs in the ICU and 7.3% (n=96/1312) prior to ICU admission. The total number of PIs was 311, of which 148 (47.6%) were acquired in the ICU. The location of majority of these PIs was the sacral area, followed by the heels. Braden score and prior length of ICU stay were associated with PI development. CONCLUSIONS: The prevalence and the stage of severity of PIs were generally low in adult critically ill patients admitted to participating UK ICUs during the study period. However, PIs are a problem in an important minority of patients. Lower Braden score and longer length of ICU stay were associated with the development of injuries; most ICUs assess risk using tools which do not account for this. TRIAL REGISTRATION NUMBER: NCT03270345

A Study of the Quasi-elastic (e,e'p) Reaction on 12^{12}C, 56^{56}Fe and 97^{97}Au

We report the results from a systematic study of the quasi-elastic (e,e'p) reaction on $^{12}$C, $^{56}$Fe and $^{197}$Au performed at Jefferson Lab. We have measured nuclear transparency and extracted spectral functions (corrected for radiation) over a Q$^2$ range of 0.64 - 3.25 (GeV/c)$^2$ for all three nuclei. In addition we have extracted separated longitudinal and transverse spectral functions at Q$^2$ of 0.64 and 1.8 (GeV/c)$^2$ for these three nuclei (except for $^{197}$Au at the higher Q$^2$). The spectral functions are compared to a number of theoretical calculations. The measured spectral functions differ in detail but not in overall shape from most of the theoretical models. In all three targets the measured spectral functions show considerable excess transverse strength at Q$^2$ = 0.64 (GeV/c)$^2$, which is much reduced at 1.8 (GeV/c)$^2$.Comment: For JLab E91013 Collaboration, 19 pages, 20 figures, 3 table

Older patients' attitudes towards and experiences of patient-physician end-of-life communication: a secondary analysis of interviews from British, Dutch and Belgian patients

<p>Abstract</p> <p>Background</p> <p>Older patients often experience sub-standard communication in the palliative phase of illness. Due to the importance of good communication in patient-centred end-of-life care, it is essential to understand the factors which influence older patients’ communication with physicians. This study examines older patients’ attitudes towards, and experiences of, patient-physician end-of-life (EoL) communication in three European countries.</p> <p>Methods</p> <p>A secondary analysis of interviews from British, Dutch and Belgian patients over the age of 60 with a progressive terminal illness was conducted. Cross-cutting themes were identified using a thematic approach.</p> <p>Results</p> <p>Themes from 30 interviews (Male n = 20, Median age 78.5) included: confidence and trust; disclosure and awareness; and participation in decision-making. Confidence and trust were reinforced by physicians’ availability, time and genuine attention and hindered by misdiagnoses and poor communication style. Most participants preferred full disclosure, though some remained deliberately ill-informed to avoid distress. Patients expressed a variety of preferences for and experiences of involvement in medical EoL decision-making and a few complained that information was only provided about the physician's preferred treatment.</p> <p>Conclusions</p> <p>A variety of experiences and attitudes regarding disclosure and participation in decision-making were reported from each country, suggesting that communication preferences are highly individual. It is important that physicians are sensitive to this diversity and avoid stereotyping. In regard to communication style, physicians are advised to provide clear explanations, avoid jargon, and continually check understanding. Both the ‘informed’ and the ‘shared’ patient-physician decision-making models assume patients make rational choices based on a clear understanding of treatment options. This idealized situation was often not reflected in patients’ experiences.</p

Average polarization of 12B in 12C(μ, ν) 12B(g.s.) reaction: Helicity of the π-decay muon and nature of the weak coupling

The helicity, h -, of μ - in π-decay has been determined as positive (h -≥+0.90) from the average polarization, P av≡〈J B·s μ〉, of 12B produced in the μ -+ 12C→ν μ+ 12B reaction. We obtain also dynamical information on μ-capture: (i) the weak magnetism form factor, μ=4.5±1.1, and (ii) the sum of the induced pseudoscalar (g p) and the 2nd class induced tensor (g T) couplings versus g A, ( g P+g T) g A=7.1±2.7. The latter result, adopting the "canonical" value of g P g A, leads to g T g A=+1±2.7 which is compatible with zero and in strong contradiction with the value {reversed tilde equals}-6 recently advocated by Kubodera, Delorme and Rho. © 1977

Euthanasia and other end-of-life decisions: a mortality follow-back study in Belgium

BACKGROUND: This study compares prevalence and types of medical end-of-life decisions between the Dutch-speaking and French-speaking communities of Belgium. This is the first nationwide study that can make these comparisons and the first measurement after implementation of the euthanasia law (2002). METHODS: We performed a mortality follow-back study in 2005-2006. Data were collected via the nationwide Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all Belgian GPs.Weekly, all GPs reported the medical end-of-life decisions among all non-sudden deaths of patients in their practice. We compared the northern Dutch-speaking (60%) and southern French-speaking communities (40%) controlling for population differences. RESULTS: We analysed 1690 non-sudden deaths. An end-of-life decision with possible life-shortening effect was made in 50% of patients in the Dutch-speaking community and 41% of patients in the French-speaking community (OR 1.4; 95%CI, 1.2 to 1.8). Continuous deep sedation until death occurred in 8% and 15% respectively (OR 0.5; 95%CI, 0.4 to 0.7). Community differences regarding the prevalence of euthanasia or physician-assisted suicide were not significant.Community differences were more present among home/care home than among hospital deaths: non-treatment decisions with explicit life-shortening intention were made more often in the Dutch-speaking than in the French-speaking community settings (OR 2.2; 95%CI, 1.2 to 3.9); while continuous deep sedation occurred less often in the Dutch-speaking community settings (OR 0.5; 95%CI, 0.3 to 0.9). CONCLUSION: Even though legal and general healthcare systems are the same for the whole country, there are considerable variations between the communities in type and prevalence of certain end-of-life decisions, even after controlling for population difference