Synchronization by small time delays

AbstractSynchronization is a phenomenon observed in all of the living and in much of the non-living world, for example in the heart beat, Huygens’ clocks, the flashing of fireflies and the clapping of audiences. Depending on the number of degrees of freedom involved, different mathematical approaches have been used to describe it, most prominently integrate-and-fire oscillators and the Kuramoto model of coupled oscillators. In the present work, we study a very simple and general system of smoothly evolving oscillators, which continue to interact even in the synchronized state. We find that under very general circumstances, synchronization generically occurs in the presence of a (small) time delay. Strikingly, the synchronization time is inversely proportional to the time delay

Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n=16) and normal (n=15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUCDCI-IPG), AUCinsulin, and AUCDCI-IPG/AUCinsulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUCDCI-IPG/AUCinsulin at baseline and a significant relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0003), which was not present in controls. Weight loss was similar between PCOS (−4.08 kg) and normal women (−4.29 kg, p=0.6281). Weight loss in PCOS women did not change the relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0100), and this relationship remained absent in control women. Conclusion. The association between AUCDCI-IPG/AUCinsulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity

Population-specific material properties of the implantation site for transcatheter aortic valve replacement finite element simulations

Patient-specific computational models are an established tool to support device development and test under clinically relevant boundary conditions. Potentially, such models could be used to aid the clinical decision-making process for percutaneous valve selection; however, their adoption in clinical practice is still limited to individual cases. To be fully informative, they should include patient-specific data on both anatomy and mechanics of the implantation site. In this work, fourteen patient-specific computational models for transcatheter aortic valve replacement (TAVR) with balloon-expandable Sapien XT devices were retrospectively developed to tune the material parameters of the implantation site mechanical model for the average TAVR population. Pre-procedural computed tomography (CT) images were post-processed to create the 3D patient-specific anatomy of the implantation site. Balloon valvuloplasty and device deployment were simulated with finite element (FE) analysis. Valve leaflets and aortic root were modelled as linear elastic materials, while calcification as elastoplastic. Material properties were initially selected from literature; then, a statistical analysis was designed to investigate the effect of each implantation site material parameter on the implanted stent diameter and thus identify the combination of material parameters for TAVR patients. These numerical models were validated against clinical data. The comparison between stent diameters measured from post-procedural fluoroscopy images and final computational results showed a mean difference of 2.5 ± 3.9%. Moreover, the numerical model detected the presence of paravalvular leakage (PVL) in 79% of cases, as assessed by post-TAVR echocardiographic examination. The final aim was to increase accuracy and reliability of such computational tools for prospective clinical applications

Magnetic Resonance-Augmented Cardiopulmonary Exercise Testing Comprehensively Assessing Exercise Intolerance in Children with Cardiovascular Disease

BACKGROUND: Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)–augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease. METHODS AND RESULTS: Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute; P=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute; P=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m2) and peak (5.3±1.2 L/min per m2) values compared with controls (resting 4.3±1.2 L/min per m2 and peak 6.6±1.2 L/min per m2) and PAH patients (resting 4.5±1.1 L/min per m2 and peak 5.9±1.1 L/min per m2). Both the PAH and tetralogy of Fallot patients had blunted exercise–induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL; P=0.005). CONCLUSIONS: MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference

Epicardial myocardial strain abnormalities may identify the earliest stages of arrhythmogenic cardiomyopathy.

The aim of this cohort study was to evaluate the value of echocardiographic multilayer strain analysis in the identification of arrhythmogenic cardiomyopathy (AC) in its earliest stages in which sudden cardiac death can occurs. Twenty seven asymptomatic relatives of AC probands (mean age 39.6 ± 19.5 years, 37 % male) with a desmosomal pathogenic mutation but no additional criteria for AC (group II) were compared to age and sex-matched healthy controls (group I). In addition, 70 patients harboring a pathogenic desmosomal mutation with "definitive" diagnosis of AC (group IV), and 19 subjects with "borderline" diagnosis (group III) were also studied. A standard echocardiographic evaluation plus left (LV) and right ventricular global and regional transmural, endocardial, and epicardial longitudinal strain (LS) analysis, was performed. In group II, while LV ejection fraction, fractional shortening, and S' were not significantly reduced compared to controls, transmural global LS was significantly reduced to 19.3 ± 1.8 % in group II versus 20.9 ± 1.1 % in controls (p = 0.0003). Compared to controls, group II presented significant (p < 0.05) regional LS decrease in the basal infero-lateral, antero-lateral, latero-apical, infero-septal, and septo-apical segments. Moreover, LS of the latero-apical and the basal antero-lateral segments was significantly altered in the epicardium (p < 0.05) but not significantly in the endocardium. Global and regional LV LS analysis allows detection of AC in an early or non-diagnostic stage of the disease. Moreover, epicardial LS analysis allows the detection of abnormalities earlier than endocardial LS

Can LMs Generalize to Future Data? An Empirical Analysis on Text Summarization

Recent pre-trained language models (PLMs) achieve promising results in existing abstractive summarization datasets. However, existing summarization benchmarks overlap in time with the standard pre-training corpora and finetuning datasets. Hence, the strong performance of PLMs may rely on the parametric knowledge that is memorized during pre-training and fine-tuning. Moreover, the knowledge memorized by PLMs may quickly become outdated, which affects the generalization performance of PLMs on future data. In this work, we propose TempoSum, a novel benchmark that contains data samples from 2010 to 2022, to understand the temporal generalization ability of abstractive summarization models. Through extensive human evaluation, we show that parametric knowledge stored in summarization models significantly affects the faithfulness of the generated summaries on future data. Moreover, existing faithfulness enhancement methods cannot reliably improve the faithfulness of summarization models on future data. Finally, we discuss several recommendations to the research community on how to evaluate and improve the temporal generalization capability of text summarization models.Comment: Accepted at EMNLP 202

Comprehensive characterization of immune landscape of Indian and Western triple negative breast cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with a significant challenge to effectively manage in the clinic worldwide. Immunotherapy may be beneficial to TNBC patients if responders can be effectively identified. Here we sought to elucidate the immune landscape of TNBCs by stratifying patients into immune-specific subtypes (immunotypes) to decipher the molecular and cellular presentations and signaling events of this heterogeneous disease and associating them with their clinical outcomes and potential treatment options. EXPERIMENTAL DESIGN: We profiled 730 immune genes in 88 retrospective Indian TNBC samples using the NanoString platform, established immunotypes using non-negative matrix factorization-based machine learning approach, and validated them using Western TNBCs (n=422; public datasets). Immunotype-specific gene signatures were associated with clinicopathological features, immune cell types, biological pathways, acute/chronic inflammatory responses, and immunogenic cell death processes. Responses to different immunotherapies associated with TNBC immunotypes were assessed using cross-cancer comparison to melanoma (n=504). Tumor-infiltrating lymphocytes (TILs) and pan-macrophage spatial marker expression were evaluated. RESULTS: We identified three robust transcriptome-based immunotypes in both Indian and Western TNBCs in similar proportions. Immunotype-1 tumors, mainly representing well-known claudin-low and immunomodulatory subgroups, harbored dense TIL infiltrates and T-helper-1 (Th1) response profiles associated with smaller tumors, pre-menopausal status, and a better prognosis. They displayed a cascade of events, including acute inflammation, damage-associated molecular patterns, T-cell receptor-related and chemokine-specific signaling, antigen presentation, and viral-mimicry pathways. On the other hand, immunotype-2 was enriched for Th2/Th17 responses, CD4+ regulatory cells, basal-like/mesenchymal immunotypes, and an intermediate prognosis. In contrast to the two T-cell enriched immunotypes, immunotype-3 patients expressed innate immune genes/proteins, including those representing myeloid infiltrations (validated by spatial immunohistochemistry), and had poor survival. Remarkably, a cross-cancer comparison analysis revealed the association of immunotype-1 with responses to anti-PD-L1 and MAGEA3 immunotherapies. CONCLUSION: Overall, the TNBC immunotypes identified in TNBCs reveal different prognoses, immune infiltrations, signaling, acute/chronic inflammation leading to immunogenic cell death of cancer cells, and potentially distinct responses to immunotherapies. The overlap in immune characteristics in Indian and Western TNBCs suggests similar efficiency of immunotherapy in both populations if strategies to select patients according to immunotypes can be further optimized and implemented

Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer

"Background Gene expression profiling of breast cancer has identified two biologically distinct estrogen receptor (ER)-positive subtypes of breast cancer: luminal A and luminal B. Luminal B tumors have higher proliferation and poorer prognosis than luminal A tumors. In this study, we developed a clinically practical immunohistochemistry assay to distinguish luminal B from luminal A tumors and investigated its ability to separate tumors according to breast cancer recurrence-free and disease-specific survival. Methods Tumors from a cohort of 357 patients with invasive breast carcinomas were subtyped by gene expression profile. Hormone receptor status, HER2 status, and the Ki67 index (percentage of Ki67-positive cancer nuclei) were determined immunohistochemically. Receiver operating characteristic curves were used to determine the Ki67 cut point to distinguish luminal B from luminal A tumors. The prognostic value of the immunohistochemical assignment for breast cancer recurrence-free and disease-specific survival was investigated with an independent tissue microarray series of 4046 breast cancers by use of Kaplan–Meier curves and multivariable Cox regression. Results Gene expression profiling classified 101 (28%) of the 357 tumors as luminal A and 69 (19%) as luminal B. The best Ki67 index cut point to distinguish luminal B from luminal A tumors was 13.25%. In an independent cohort of 4046 patients with breast cancer, 2847 had hormone receptor–positive tumors. When HER2 immunohistochemistry and the Ki67 index were used to subtype these 2847 tumors, we classified 1530 (59%, 95% confidence interval [CI] = 57% to 61%) as luminal A, 846 (33%, 95% CI = 31% to 34%) as luminal B, and 222 (9%, 95% CI = 7% to 10%) as luminal–HER2 positive. Luminal B and luminal–HER2-positive breast cancers were statistically significantly associated with poor breast cancer recurrence-free and disease-specific survival in all adjuvant systemic treatment categories. Of particular relevance are women who received tamoxifen as their sole adjuvant systemic therapy, among whom the 10-year breast cancer–specific survival was 79% (95% CI = 76% to 83%) for luminal A, 64% (95% CI = 59% to 70%) for luminal B, and 57% (95% CI = 47% to 69%) for luminal–HER2 subtypes. Conclusion Expression of ER, progesterone receptor, and HER2 proteins and the Ki67 index appear to distinguish luminal A from luminal B breast cancer subtypes.

Simulation-based analysis of micro-robots swimming at the center and near the wall of circular mini-channels

Swimming micro robots have great potential in biomedical applications such as targeted drug delivery, medical diagnosis, and destroying blood clots in arteries. Inspired by swimming micro organisms, micro robots can move in biofluids with helical tails attached to their bodies. In order to design and navigate micro robots, hydrodynamic characteristics of the flow field must be understood well. This work presents computational fluid dynamics (CFD) modeling and analysis of the flow due to the motion of micro robots that consist of magnetic heads and helical tails inside fluid-filled channels akin to bodily conduits; special emphasis is on the effects of the radial position of the robot. Time-averaged velocities, forces, torques, and efficiency of the micro robots placed in the channels are analyzed as functions of rotation frequency, helical pitch (wavelength) and helical radius (amplitude) of the tail. Results indicate that robots move faster and more efficiently near the wall than at the center of the channel. Forces acting on micro robots are asymmetrical due to the chirality of the robot’s tail and its motion. Moreover, robots placed near the wall have a different flow pattern around the head when compared to in-center and unbounded swimmers. According to simulation results, time-averaged for-ward velocity of the robot agrees well with the experimental values measured previously for a robot with almost the same dimensions

Non-contact reflection photoplethysmography towards effective human physiological monitoring

A non-contact reflection photoplethysmography (NRPPG) with its engineering model was created to access human physiological information. The NRPPG engineering setup with a vertical cavity surface emitting laser (VCSEL) as a light source and a high-speed PiN photodiode as a photodetector was configured based upon the principles of light-tissue interaction and Beer-Lambert’s law. In this paper, we present three aspects of the NRPPG performance: (1) photonics engineering work to capture photoplethysmographic signals with a non-contact manner in an optimal setup of the NRPPG; (2) a 5-minute protocol with 22 participants to determine a good agreement between NRPPG and contact photoplethysmography (CPPG) by means of Bland-Altman statistical analysis and Pearson’s correlation coefficient; and (3) a physiological experiment designed for cardiac-physiological monitoring utilizing NRPPG. The experimental results suggest that clean PPG signal can be obtained between 30-110 mm. The outcome from agreement study indicates that the performance of NRPPG is compatible with CPPG. The NRPPG technique has great potential in cardiac-physiological assessment in a required clinical circumstance