Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia

Background and purpose Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Methods: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Results: Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. Conclusions: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness

The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium

[EN] Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.IRO, VMZM, HHU and PLS were supported by the Mexican National Council of Science and Technology (CONACyT) with a PhD fellowship (210085, 210100, 243380 and 219883, respectively). Work in the SDF laboratory was financed by the CONACyT grants CB-2012-177739, FC-2015-2/1061, and INFR-2015-253504, and NMM by the CONACyT grant CB-2011-165986. SDF, CF and LC acknowledge the support of the European Union FP7-PEOPLE-2009-IRSES project EVOCODE (grant no. 247587) and H2020-MSCARISE-2015 project ExpoSEED (grant no. 691109). SDF also acknowledges the Marine Biological Laboratory (MBL) in Woods Hole for a scholarship for the Gene Regulatory Networks for Development Course 2015 (GERN2015). IE acknowledges the International European Fellowship-METMADS project and the Universita degli Studi di Milano (RTD-A; 2016). Research in the laboratory of MFY was funded by NSF (grant IOS-1121055), NIH (grant 1R01GM112976-01A1) and the Paul D. Saltman Endowed Chair in Science Education (MFY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Reyes Olalde, J.; Zuñiga, V.; Serwatowska, J.; Chávez Montes, R.; Lozano-Sotomayor, P.; Herrera-Ubaldo, H.; Gonzalez Aguilera, K.... (2017). The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium. PLoS Genetics. 13(4):1-31. https://doi.org/10.1371/journal.pgen.1006726S131134Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., Chávez Montes, R. A., Marsch-Martínez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002Alvarez-Buylla, E. 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Visceral Adiposity and Severe COVID-19 Disease: Application of an Artificial Intelligence Algorithm to Improve Clinical Risk Prediction

Background: Obesity has been linked to severe clinical outcomes among people who are hospitalized with coronavirus disease 2019 (COVID-19). We tested the hypothesis that visceral adipose tissue (VAT) is associated with severe outcomes in patients hospitalized with COVID-19, independent of body mass index (BMI). Methods: We analyzed data from the Massachusetts General Hospital COVID-19 Data Registry, which included patients admitted with polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection from March 11 to May 4, 2020. We used a validated, fully automated artificial intelligence (AI) algorithm to quantify VAT from computed tomography (CT) scans during or before the hospital admission. VAT quantification took an average of 2 ± 0.5 seconds per patient. We dichotomized VAT as high and low at a threshold of ≥100 cm² and used Kaplan-Meier curves and Cox proportional hazards regression to assess the relationship between VAT and death or intubation over 28 days, adjusting for age, sex, race, BMI, and diabetes status. Results: A total of 378 participants had CT imaging. Kaplan-Meier curves showed that participants with high VAT had a greater risk of the outcome compared with those with low VAT (P < .005), especially in those with BMI <30 kg/m2 (P < .005). In multivariable models, the adjusted hazard ratio (aHR) for high vs low VAT was unchanged (aHR, 1.97; 95% CI, 1.24–3.09), whereas BMI was no longer significant (aHR for obese vs normal BMI, 1.14; 95% CI, 0.71–1.82). Conclusions: High VAT is associated with a greater risk of severe disease or death in COVID-19 and can offer more precise information to risk-stratify individuals beyond BMI. AI offers a promising approach to routinely ascertain VAT and improve clinical risk prediction in COVID-19.National Institute of Diabetes and Digestive and Kidney Diseases (Grants T32DK007028 and R01DK085070)National Heart, Lung, and Blood Institute (Grant R01HL132786)National Institute of Allergy and Infectious Diseases (Grants R01AG062393 and K24AI141036)National Institute of General Medical Sciences (Grant R01GM127862

Estimating Joint Contributions in Function Motions to Create a Metric for Injury Prevention using Motion Capture and OpenSim: A Preliminary Study

A heightened awareness of athletic safety in the field of sports has increased the development of various injury prevention studies. The predominant injury type in sports occurs with overuse and fatigue. Current methods use qualitative screening tests to determine injury proneness. However, these screening tests are subjective to each assessor, resulting in human error, inconsistent scoring and misdiagnosis of the motion. The main objective of this project is to utilize quantitative techniques to measure human movement and develop training protocols that will result in a reduced risk of athletic injury and increased performance. To develop the testing protocol, four subjects were affixed with reflective markers based on anatomical locations on the lower extremity. VICON Nexus software was used to create subject-specific models and record the subjects\u27 motions during screening tests. This data was then processed using OpenSim in which the inverse kinematics was calculated to determine the joint angles of the lumbar, hip, knee, and ankle. The data was normalized and plotted using MATLAB and compared across the four subjects. The results determined which joints were the main contributors to each motion and clearly showed similarities between the right and left legs. This metric demonstrated that the preliminary testing protocol was successful. After establishing a large subject database, the join angles of individual subjects will be compared to a more general metric to determine injury proneness