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Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations that compromise the function of cohesin, a major regulator of 3D genome organization. Cognitive impairment is a universal and as yet unexplained feature of CdLS. We characterized the transcriptional profile of cortical neurons from CdLS patients and found deregulation of hundreds of genes enriched for neuronal functions related to synaptic transmission, signalling processes, learning and behaviour. Inducible proteolytic cleavage of cohesin disrupted 3-D genome organization and transcriptional control in post-mitotic cortical mouse neurons. The genes affected belonged to similar gene ontology classes and showed significant numerical overlap with those deregulated in CdLS. Interestingly, gene expression was largely rescued by subsequent reconstitution of cohesin function. These experiments show that cohesin is continuously required for neuronal gene expression and provide a tractable approach for addressing mechanisms of neuronal dysfunction in CdLS.

Study objective: The Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) is a validated clinical decision tool that characterizes risk of mortality in emergency department (ED) acute heart failure patients. The objective of this study is to compare the distribution of risk categories between hospitalized and discharged ED patients with acute heart failure. Methods: We included consecutive acute heart failure patients from 34 Spanish EDs. Patients were retrospectively classified according to MEESSI-AHF risk categories. We calculated the odds of hospitalization (versus direct discharge from the ED) across MEESSI-AHF risk categories. Next, we assessed the following 30-day postdischarge outcomes: ED revisit, hospitalization, death, and their combination. We used Cox hazards models to determine the adjusted association between ED disposition decision and the outcomes among patients who were stratified into low-and increased-risk categories. Results: We included 7,930 patients (80.5 years [SD 10.1 years]; women 54.7%; hospitalized 75.3%). Compared with that for low-risk MEESSI-AHF patients, odds ratios for hospitalization of patients in intermediate-, high-, and very-high-risk categories were 1.83 (95% confidence interval [CI] 1.64 to 2.05), 3.05 (95% CI 2.48 to 3.76), and 3.98 (95% CI 3.13 to 5.05), respectively. However, almost half (47.6%) of all discharged patients were categorized as being at increased risk by MEESSI-AHF, and 19.0% of all the increased-risk patients were discharged from the ED. Among the low-risk MEESSI-AHF patients, the 30-day postdischarge mortality did not differ by ED disposition (hazard ratio [HR] for discharged patients with respect to hospitalized ones 0.65; 95% CI 0.70 to 1.11), nor did it differ in the increased-risk group (HR 0.88; 95% CI 0.63 to 1.23). The discharged low-risk MEESSI-AHF patients had higher risks of 30-day ED revisit and hospitalization (HR 1.86, 95% CI 1.57 to 2.20; and HR 1.92, 95% CI 1.54 to 2.40, respectively) compared with the admitted patients, as did the discharged patients in the increased-risk group (HR 1.62, 95% CI 1.39 to 1.89; and HR 1.40, 95% CI 1.16 to 1.68, respectively), with similar results for the combined endpoint. Conclusion: The disposition decisions made in current clinical practice for ED acute heart failure patients calibrate with MEESSI-AHF risk categories, but nearly half of the patients currently discharged from the ED fall into increased-risk MEESSI-AHF categories.

Study objective: We assess the value of the Barthel Index (BI) in predicting 30-day mortality risk among patients with acute heart failure who are attending the emergency department (ED). Methods: We selected 9,098 acute heart failure patients from the Acute Heart Failure in Emergency Departments registry who had BI score available both at baseline and the ED visit. Patients' data were collected from 41 Spanish hospitals during four 1- to 2-month periods between 2009 and 2016. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and BI score. c Statistics were used to estimate their prognostic value. Results: The mean baseline BI score was 79.4 (SD 24.6) and the mean ED BI score was 65.3 (SD 29.1). Acute functional decline (>= 5-point decrease between baseline BI and ED BI score) was observed in 5,771 patients (53.4%). Within 30 days of the ED visit, 905 patients (9.9%) died. There was a steep inverse gradient in 30-day mortality risk for baseline BI and ED BI score. For instance, compared with BI score=100, a BI score of 50 to 55 doubled the mortality risk both at baseline and the ED visit. At the ED visit, a BI score of 0 to 5 carried a 5-fold increase in risk after adjustment for other risk predictors. In comparison with baseline BI score, ED BI score consistently provided greater discrimination. Neither baseline BI score nor the change in BI score from baseline to the ED visit added further prognostic value to the ED BI score. Conclusion: Functional status assessed by the BI score at the ED visit is a strong predictor of 30-day mortality in acute heart failure patients, with higher predictive value than baseline BI score and acute functional decline. Routine recording of BI score at the ED visit may help in decisionmaking and health care planning.

Objective. To determine the rate of adverse events in patients with acute heart failure (AHF) who were discharged from the emergency department (ED) after classification as low risk according to MEESSI score (multiple risk estimate based on the Spanish ED scale), to analyze the ability of the score to predict events, and to explore variables associated with adverse events. Methods. Patients in the EAHFE registry (Epidemiology of Acute Heart Failure in EDs) were stratified according to risk indicated by MEESSI score in order to identify those considered at low risk on discharge. All-cause 30-day mortality and revisits related to AHF within 7 days and 30 days were recorded. The area under the receiver operating characteristic curve (AUC) was calculated for the MEESSI score's ability to predict these events. Associations between 42 variables and 7-day and 30-day revisits to the ED were analyzed by multivariable logistic regression. Results. A total of 1028 patients were included. The 30-day mortality rate was 1.6% (95% CI, 0.9%-2.5%). The 7-day and 30-day revisit rates were 8.0% (95% CI, 6.4%-9.8%) and 24.7% (95% CI, 22.1%-25.7%), respectively. The AUCs for MEESSI score discrimination between patients with and without these outcomes were as follows: 30-day mortality, 0.69 (95% CI, 0.58-0.80); 7-day revisiting, 0.56 (95% CI, 0.49-0.63); and 30-day revisiting, 0.54 (95% CI, 0.50-0.59). Variables associated with 7-day revisits were long-term diuretic treatment (odds ratio [OR], 2.45; 95% CI, 1.01-5.98), hemoglobin concentration less than 110 g/L (OR, 1.68; 95% CI, 1.02-2.75), and intravenous diuretic treatment in the ED (OR, 0.53; 95% CI, 0.31-0.90). Variables associated with 30-day revisits were peripheral artery disease (OR, 1.74; 95% CI, 1.01-3.00), prior history of an AHF episode (OR, 1.42; 95% CI, 1.02-1.98), long-term mineralocorticoid receptor antagonist treatment (OR, 1.71; 95% CI, 1.09-2.67), Barthel index less than 90 points in the ED (OR, 1.48; 95% CI, 1.07-2.06), and intravenous diuretic treatment in the ED (OR, 0.58; 95% CI, 0.40-0.84). Conclusions. Patients with AHF who are at low risk for adverse events on discharge from our EDs have event rates that are near internationally recommended targets. The MEESSI score, which was designed to predict 30-day mortality, is a poor predictor of 7-day or 30-day revisiting in these low-risk patients. We identified other factors related to these events.

Study objective: We assess the value of the Barthel Index (BI) in predicting 30-day mortality risk among patients with acute heart failure who are attending the emergency department (ED). Methods: We selected 9,098 acute heart failure patients from the Acute Heart Failure in Emergency Departments registry who had BI score available both at baseline and the ED visit. Patients' data were collected from 41 Spanish hospitals during four 1- to 2-month periods between 2009 and 2016. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and BI score. c Statistics were used to estimate their prognostic value. Results: The mean baseline BI score was 79.4 (SD 24.6) and the mean ED BI score was 65.3 (SD 29.1). Acute functional decline (>= 5-point decrease between baseline BI and ED BI score) was observed in 5,771 patients (53.4%). Within 30 days of the ED visit, 905 patients (9.9%) died. There was a steep inverse gradient in 30-day mortality risk for baseline BI and ED BI score. For instance, compared with BI score=100, a BI score of 50 to 55 doubled the mortality risk both at baseline and the ED visit. At the ED visit, a BI score of 0 to 5 carried a 5-fold increase in risk after adjustment for other risk predictors. In comparison with baseline BI score, ED BI score consistently provided greater discrimination. Neither baseline BI score nor the change in BI score from baseline to the ED visit added further prognostic value to the ED BI score. Conclusion: Functional status assessed by the BI score at the ED visit is a strong predictor of 30-day mortality in acute heart failure patients, with higher predictive value than baseline BI score and acute functional decline. Routine recording of BI score at the ED visit may help in decisionmaking and health care planning.

Study objective: The Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) is a validated clinical decision tool that characterizes risk of mortality in emergency department (ED) acute heart failure patients. The objective of this study is to compare the distribution of risk categories between hospitalized and discharged ED patients with acute heart failure. Methods: We included consecutive acute heart failure patients from 34 Spanish EDs. Patients were retrospectively classified according to MEESSI-AHF risk categories. We calculated the odds of hospitalization (versus direct discharge from the ED) across MEESSI-AHF risk categories. Next, we assessed the following 30-day postdischarge outcomes: ED revisit, hospitalization, death, and their combination. We used Cox hazards models to determine the adjusted association between ED disposition decision and the outcomes among patients who were stratified into low-and increased-risk categories. Results: We included 7,930 patients (80.5 years [SD 10.1 years]; women 54.7%; hospitalized 75.3%). Compared with that for low-risk MEESSI-AHF patients, odds ratios for hospitalization of patients in intermediate-, high-, and very-high-risk categories were 1.83 (95% confidence interval [CI] 1.64 to 2.05), 3.05 (95% CI 2.48 to 3.76), and 3.98 (95% CI 3.13 to 5.05), respectively. However, almost half (47.6%) of all discharged patients were categorized as being at increased risk by MEESSI-AHF, and 19.0% of all the increased-risk patients were discharged from the ED. Among the low-risk MEESSI-AHF patients, the 30-day postdischarge mortality did not differ by ED disposition (hazard ratio [HR] for discharged patients with respect to hospitalized ones 0.65; 95% CI 0.70 to 1.11), nor did it differ in the increased-risk group (HR 0.88; 95% CI 0.63 to 1.23). The discharged low-risk MEESSI-AHF patients had higher risks of 30-day ED revisit and hospitalization (HR 1.86, 95% CI 1.57 to 2.20; and HR 1.92, 95% CI 1.54 to 2.40, respectively) compared with the admitted patients, as did the discharged patients in the increased-risk group (HR 1.62, 95% CI 1.39 to 1.89; and HR 1.40, 95% CI 1.16 to 1.68, respectively), with similar results for the combined endpoint. Conclusion: The disposition decisions made in current clinical practice for ED acute heart failure patients calibrate with MEESSI-AHF risk categories, but nearly half of the patients currently discharged from the ED fall into increased-risk MEESSI-AHF categories.

Background: Little is known about the prevalence and impact of risk of malnutrition on short-term mortality among seniors presenting with acute heart failure (AHF) in emergency setting. The objective was to determine the impact of risk of malnutrition on 30-day mortality risk among older patients who attended in Emergency Departments (EDs) for AHF. Material and methods: We performed a secondary analysis of the OAK-3 Registry including all consecutive patients >= 65 years attending in 16 Spanish EDs for AHF. Risk of malnutrition was defined by the Mini Nutritional Assessment Short Form (MNA-SF) < 12 points. Unadjusted and adjusted logistic regression models were used to assess the association between risk of malnutrition and 30-day mortality. Results: We included 749 patients (mean age: 85 (SD 6); 55.8% females). Risk of malnutrition was observed in 594 (79.3%) patients. The rate of 30-day mortality was 8.8%. After adjusting for MEESSI-AHF risk score clinical categories (model 1) and after adding all variables showing a significantly different distribution among groups (model 2), the risk of malnutrition was an independent factor associated with 30-day mortality (adjusted OR by model 1 = 3.4; 95% CI 1.2-9.7; p = .020 and adjusted OR by model 2 = 3.1; 95% CI 1.1-9.0; p = .033) compared to normal nutritional status. Conclusions: The risk of malnutrition assessed by the MNA-SF is associated with 30-day mortality in older patients with AHF who were attended in EDs. Routine screening of risk of malnutrition may help emergency physicians in decision-making and establishing a care plan.

[EN] Articles from different areas which are closely related to the modelling of the stator of travelling wave ultrasonic motors (TWUMs) are reviewed in this work. Thus, important issues relevant to this problem are identified from the areas of vibration of annular plates, laminated plate theories, and modelling of piezoelectric transducers. From this integrated point of view, it becomes clear that there are some very important issues yet to be addressed in the modelling of TWUMs. Firstly, the influence of material properties and stator dimensions on output efficiency, electromechanical coupling coefficients (EMCC) and maximum output energy is to be investigated in more detail. Secondly, the modelling of the electric potential field (by explicitly including the charge equation) for TWUMs seems to be a must for better prediction of displacements and electric fields close to the resonance, as suggested by some recent works [1]. Moreover, the improvement of current models by using shear deformation (or higher order) laminated plate theories (LPTs) in conjunction with approximated methods of solution are discussed. In addition to analytical models, those works using Finite Element and Finite difference Methods (FEM and FDM) for the modelling and simulation of the TWUM stator dynamics are reviewed., [ES] En este trabajo se realiza una revisión de los trabajos de investigación realizados en diversas áreas sobre el modelado del estátor de los motores ultrasónicos de onda viajera (TWUMs). Entre los problemas relevantes que se han estudiado podemos citar la vibración de placas anulares, las teorías de placas laminadas y el modelado de transductores piezoeléctricos. A raíz de este punto de vista integral se hace manifiesto que todavía quedan asuntos importantes que estudiar en el modelado de los TWUMs. En primer lugar, la influencia de las propiedades del material y las dimensiones del estátor en la eficiencia del motor, los coeficientes de acoplamiento electromecánico (EMCC) y la máxima energía entregada deberían ser estudiados más detenidamente. En segundo lugar, el modelado de la distribución del campo eléctrico en los TWUMs (incluyendo la ecuación de carga explícitamente) parece imprescindible para lograr una predicción mejor del desplazamiento y del campo eléctrico cerca de la resonancia, como se ha apuntado en referencias actuales [1]. Además, se discute las mejoras que incorporaría a los modelos existentes en la actualidad la inclusión de las teorías de placas laminadas (LPTs) con deformaciones de corte (o de orden superior), resueltas mediante métodos aproximados. Como complemento a los modelos analíticos, se realiza asimismo una revisión de las técnicas de elementos finitos (FEM) y diferencias finitas (FDM) empleadas en la simulación de la dinámica del estátor de los motores TWUM., The authors are thankful for the support from the National Science and Research Office (Senacyt), the Institute for Human Resource Development and Proficiency (IFARHU), both of Panama, and the European Union for its support through grant DE-4205.