Usefulness of regional right ventricular and right atrial strain for prediction of early and late right ventricular failure following a left ventricular assist device implant: A machine learning approach

Background: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. Methods: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute–right ventricular failure (N = 8, 11%) or chronic–right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an “all-subsets” approach. Results: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular–free wall were the most significant predictors of acute–right ventricular failure (maximum receiver operating characteristic–area under the curve = 0.95, 95% confidence interval = 0.91–1.00, by the naïve Bayes), while the right ventricular–free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic–area under the curve = 0.97, 95% confidence interval = 0.91–1.00, according to naïve Bayes). Conclusion: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute–right ventricular failure and chronic–right ventricular failure, respectively

Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.Wellcome Trust MR

Patterns of ascending aortic dilatation and predictors of surgical replacement of the aorta: A comparison of bicuspid and tricuspid aortic valve patients over eight years of follow-up

Background: Predictors of thoracic aorta growth and early cardiac surgery in patients with bicuspid aortic valve are undefined. Our aim was to identify predictors of ascending aorta dilatation and cardiac surgery in patients with bicuspid aortic valve (BAV). Methods: Forty-one patients with BAV were compared with 165 patients with tricuspid aortic valve (TAV). All patients had LV EF > 50%, normal LV dimensions, and similar degree of aortic root or ascending aorta dilatation at enrollment. Patients with more than mild aortic stenosis or regurgitation were excluded. A CT-scan was available on 76% of the population, and an echocardiogram was repeated every year for a median time of 4 years (range: 2 to 8 years). Patterns of aortic expansion in BAV and TAV groups were analyzed by a mixed-effects longitudinal linear model. In the time-to-event analysis, the primary end point was elective or emergent surgery for aorta replacement. Results: BAV patients were younger, while the TAV group had greater LV wall thickness, arterial hypertension, and dyslipidemia than BAV patients. Growth rate was 0.46 ± 0.04 mm/year, similar in BAV and TAV groups (p = 0.70). Predictors of cardiac surgery were aorta dimensions at baseline (HR 1.23, p = 0.01), severe aortic regurgitation developed during follow-up (HR 3.49, p 0.04), family history of aortic aneurysm (HR 4.16, p 1.73), and history of STEMI (HR 3.64, p < 0.001). Conclusions: Classic baseline risk factors were more commonly observed in TAV aortopathy compared with BAV aortopathy. However, it is reassuring that, though diagnosed with aneurysm on average 10 years earlier and in the absence of arterial hypertension, BAV patients had a relatively low growth rate, similar to patients with a tricuspid valve. Irrespective of aortic valve morphology, patients with a family history of aortic aneurysm, history of coronary artery disease, and those who developed severe aortic regurgitation at follow-up, had the highest chances of being referred for surgery

Seizures as the first manifestation of chromosome 22q11.2 deletion syndrome in a 40-year old man: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Quantum Theory of MIMO Markovian Feedback with Diffusive Measurements

Feedback control engineers have been interested in MIMO (multiple-input multiple-output) extensions of SISO (single-input single-output) results of various kinds due to its rich mathematical structure and practical applications. An outstanding problem in quantum feedback control is the extension of the SISO theory of Markovian feedback by Wiseman and Milburn [Phys. Rev. Lett. {\bf 70}, 548 (1993)] to multiple inputs and multiple outputs. Here we generalize the SISO homodyne-mediated feedback theory to allow for multiple inputs, multiple outputs, and \emph{arbitrary} diffusive quantum measurements. We thus obtain a MIMO framework which resembles the SISO theory and whose additional mathematical structure is highlighted by the extensive use of vector-operator algebra.Comment: 17 pages, 2 figure

Evaluating the influence of progesterone concentration and time of exposure on in vitro endometrial decidualisation

This study aimed to evaluate the influence of progesterone (concentration and time of exposure) on endometrial decidualisation using an in vitro model cell line: Human Endometrial Stromal Cells (HESCs). HESCs exposed to progesterone (1 and 10 μM) had higher percentages of decidualised cells and higher expression of the decidual marker (Insulin Like Growth Factor Binding Protein 1 (IGFBP1)) compared with those exposed to (0.1 μM). Among those HESCs cultured with 1 μM progesterone for 11 days, the highest rate of morphological differentiation (40–50%) occurred between days 7–9 and IGFBP1 peaked on day 7. The cell-cycle pathway was significantly down-regulated in HESCs exposed to at least 1 μM progesterone regardless of the incubation period. We conclude that exposure to high progesterone concentration for 7–9 days is essential to maximise the process of decidualisation

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation

Background: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. Objectives: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. Methods: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. Results: Among 2,425 patients (age 67 \ub1 13 years; 71% male, 67% asymptomatic, ejection fraction 64 \ub1 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 \ub1 1%, 59 \ub1 3%, and 46 \ub1 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 \ub1 1%, 70 \ub1 4%, and 57 \ub1 3%, respectively; p < 0.0001). Conclusions: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery

Domesticating Fears and Fantasies of ‘the East’: integrating the Ottoman legacy within European heritage

'Europe' has no fixed geographical, historical, religious or cultural boundaries. Claims for the existence of European civilization as a discrete construct are continually made yet dissolve on close scrutiny. Here, we examine these claims at one of the grandest points of existential crisis and belonging for Europe, the relationship with the 'Other within': Turkey, the Balkans and Ottoman heritage in Europe. Through a hybrid semiotic and Foucauldian analysis of catalogues of eight high-profile exhibitions in the United Kingdom, Turkey, Belgium and Portugal we argue that an unsettled discursive struggle is at play, in which one 'Europe' articulates 'reconciliation' of profound civilizational difference while another, Ottoman, 'Europe' stakes a claim of right as an intrinsic component of what it means to be European in a contemporary context. We attempt to trace the role of museum marketing in the perennial accommodation/exclusion of the Ottoman Empire as an intrinsic component in the diversity of Europe’s cultural heritage