3D tomography of cells in micro-channels

We combine confocal imaging, microfluidics and image analysis to record 3D-images of cells in flow. This enables us to recover the full 3D representation of several hundred living cells per minute. Whereas 3D confocal imaging has thus far been limited to steady specimen, we overcome this restriction and present a method to access the 3D shape of moving objects. The key of our principle is a tilted arrangement of the micro-channel with respect to the focal plane of the microscope. This forces cells to traverse the focal plane in an inclined manner. As a consequence, individual layers of passing cells are recorded which can then be assembled to obtain the volumetric representation. The full 3D information allows for a detailed comparisons with theoretical and numerical predictions unfeasible with e.g.\ 2D imaging. Our technique is exemplified by studying flowing red blood cells in a micro-channel reflecting the conditions prevailing in the microvasculature. We observe two very different types of shapes: `croissants' and `slippers'. Additionally, we perform 3D numerical simulations of our experiment to confirm the observations. Since 3D confocal imaging of cells in flow has not yet been realized, we see high potential in the field of flow cytometry where cell classification thus far mostly relies on 1D scattering and fluorescence signals

Determination of the Boltzmann constant k from the speed of sound in helium gas at the triple point of water

partially_open6The Boltzmann constant k has been determined from a measurement of the speed of sound in helium gas in a quasi-spherical resonator (volume 0.5 l) maintained at a temperature close to the triple point of water (273.16 K). The acoustic velocity c is deduced from measured acoustic resonance frequencies and the dimensions of the quasi-sphere, the latter being obtained via simultaneous microwave resonance. Values of c are extrapolated to the zero pressure limit of ideal gas behaviour. We find J⋅K−1, a result consistent with previous measurements in our group and elsewhere. The value for k, which has a relative standard uncertainty of 1.02 ppm, lies 0.02 ppm below that of the CODATA 2010 adjustment.mixedPitre, L; Risegari, L; Sparasci, F; Plimmer, M D; Himbert, M E; Giuliano Albo, P APitre, L; Risegari, L; Sparasci, F; Plimmer, M D; Himbert, M E; Giuliano Albo, P

C-Reactive Protein Levels in the Brugada Syndrome

Background. Inflammation in the Brugada syndrome (BrS) and its clinical implication have been little studied. Aims. To assess the level of inflammation in BrS patients. Methods. All studied BrS patients underwent blood samples drawn for C-reactive protein (CRP) levels at admission, prior to any invasive intervention. Patients with a previous ICD placement were controlled to exclude those with a recent (<14 days) shock. We divided subjects into symptomatic (syncope or aborted sudden death) and asymptomatic groups. In a multivariable analysis, we adjusted for significant variables (age, CRP ≥ 2 mg/L). Results. Fifty-four subjects were studied (mean age 45 ± 13 years, 49 (91%) male). Twenty (37%) were symptomatic. Baseline characteristics were similar in both groups. Mean CRP level was 1,4 ± 0,9 mg/L in asymptomatic and 2,4 ± 1,4 mg/L in symptomatic groups (P = .003). In the multivariate model, CRP concentrations ≥ 2 mg/L remained an independent marker for being symptomatic (P = .018; 95% CI: 1.3 to 19.3). Conclusion. Inflammation seems to be more active in symptomatic BrS. C-reactive protein concentrations ≥ 2 mg/L might be associated with the previous symptoms in BrS. The value of inflammation as a risk factor of arrhythmic events in BrS needs to be studied

Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever

Quantum dynamics of molecules in 4He nano-droplets: Microscopic Superfluidity

High resolution spectroscopy of doped molecules in 4He nano-droplets and clusters gives a signature of superfluidity in microscopic system, termed as microscopic superfluidity. Ro-vibrational spectrum of 4HeN-M clusters is studied with the help of some important observations, revealed from experiments (viz., localised and orderly arrangement of 4He atoms, although, being free to move in the order of their locations; individual 4He atoms can not be tagged as normal/ superfluid, etc.) and other factors (e.g., consideration that the 4He atoms which happen to fall in the plane of rotation of a molecule, render a equipotential ring and thus, do not take part in rotation; etc.) which effect the rotational and vibrational spectrum of the system. This helps us in successfully explaining the experimental findings which state that the rotational spectrum of clusters have sharp peaks (indicating that the molecule rotates like a free rotor) and moment of inertia and vibrational frequency shift have a non-trivial dependence on N

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (&gt;21 and &lt;25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis

The "smoker's paradox" in patients with acute coronary syndrome: a systematic review

<p>Abstract</p> <p>Background</p> <p>Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival benefit for smokers; that is, the "smoker's paradox". The aim of this study was, therefore, to perform a systematic review of the literature and evidence surrounding the existence of the "smoker's paradox".</p> <p>Methods</p> <p>Relevant studies published by September 2010 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1963) and the Cochrane Central Register of Controlled Trials, with a combination of text words and subject headings used. English-language original articles were included if they presented data on hospitalised patients with defined acute coronary syndrome, reported at least in-hospital mortality, had a clear definition of smoking status (including ex-smokers), presented crude and adjusted mortality data with effect estimates, and had a study sample of > 100 smokers and > 100 non-smokers. Two investigators independently reviewed all titles and abstracts in order to identify potentially relevant articles, with any discrepancies resolved by repeated review and discussion.</p> <p>Results</p> <p>A total of 978 citations were identified, with 18 citations from 17 studies included thereafter. Six studies (one observational study, three registries and two randomised controlled trials on thrombolytic treatment) observed a "smoker's paradox". Between the 1980s and 1990s these studies enrolled patients with acute myocardial infarction (AMI) according to criteria similar to the World Health Organisation criteria from 1979. Among the remaining 11 studies not supporting the existence of the paradox, five studies represented patients undergoing contemporary management.</p> <p>Conclusion</p> <p>The "smoker's paradox" was observed in some studies of AMI patients in the pre-thrombolytic and thrombolytic era, whereas no studies of a contemporary population with acute coronary syndrome have found evidence for such a paradox.</p

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes