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At least 127 records · Page 7Linked to original sources

Polyhazard models for lifetime data.

We propose a polyhazard model to deal with lifetime data associated with latent competing risks. The causes of failure are assumed unobserved and affecting individuals independently. The general framework allows a broad class of hazard models that includes the most common hazard-based models. The model accommodates bathtub and multimodal hazards, keeping enough flexibility for common lifetime data that cannot be accommodated by usual hazard-based models. Maximum likelihood estimation is discussed, and parametric simulation is used for hypothesis testing.

Animals↗

Fano resonances in prism-coupled multimode square micropillar resonators.

We report Fano resonances in a multimode square glass micropillar resonator; the resonances were obtained by using angle-resolved prism coupling. Our experiments reveal characteristically asymmetric line shapes of high-Q resonances and of detuned low-Q resonances in multimode reflection spectra. The asymmetric resonance line shapes evolve for an approximately pi phase within a 0.5 degree range of reflection angles. We model our observed asymmetric multimode resonances by the far-field interference between a light wave that is evanescently coupled with a high-Q mode orbit and a coherent light wave that is refractively coupled with a detuned low-Q mode orbit.

Journal Article↗

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator.

BACKGROUND: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. METHODS: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum." A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. RESULTS: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. CONCLUSIONS: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions.

Abdominal Neoplasms↗

Efficiency of DNA replication in the polymerase chain reaction.

A detailed quantitative kinetic model for the polymerase chain reaction (PCR) is developed, which allows us to predict the probability of replication of a DNA molecule in terms of the physical parameters involved in the system. The important issue of the determination of the number of PCR cycles during which this probability can be considered to be a constant is solved within the framework of the model. New phenomena of multimodality and scaling behavior in the distribution of the number of molecules after a given number of PCR cycles are presented. The relevance of the model for quantitative PCR is discussed, and a novel quantitative PCR technique is proposed.

DNA Replication↗

[Theory of cooperative transition of DNA complexes with multimodal ligands].

The theory of the cooperative transition of DNA.ligand complexes have been developed, in which a model was implied where the multimodal ligands simultaneously interacted with DNA. Obtained formula express the dependence of the experimentally estimated values of the changes of transition point and width of transition on the concentration of the ligands. These expressions make possible to obtain the thermodynamic parameters of the interaction of the multimodal ligands with DNA (binding constants, number of base pairs corresponding to one binding site of DNA etc.) by comparing the theoretical and the experimental data.

DNA↗

What's special about personally familiar faces? A multimodal approach.

Dual-route models of face recognition suggest separate cognitive and affective routes. The predictions of these models were assessed in recognition tasks with unfamiliar, famous, and personally familiar faces. Whereas larger autonomic responses were only triggered for personally familiar faces, priming effects in reaction times to these faces, presumably reflecting cognitive recognition processes, were equal to those of famous faces. Activation of stored structural representations of familiar faces (face recognition units) was assessed by recording the N250r component in event-related brain potentials. Face recognition unit activation increased from unfamiliar over famous to personally familiar faces, suggesting that there are stronger representations for personally familiar than for famous faces. Because the topographies of the N250r for personally and famous faces were indistinguishable, a similar network of face recognition units can be assumed for both types of faces.

Adult↗

Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior. METHODS: This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia. RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. CONCLUSION: This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

Adult↗

Multimodal assessment of the primary healthcare system of Serbia: a model for evaluating post-conflict health systems.

INTRODUCTION: Conflicts, social unrest, and disasters can significantly affect the ability of a healthcare system to provide for the needs of its citizens. The collapse of the primary healthcare system in Serbia is a model of the effects that civil unrest can have on the health of a population. However, with improving social and political conditions, focus now can be turned towards the greatly needed development and reorganization of the primary healthcare system in Serbia. Due to the complexity of health-system reform in the post-conflict/post-disaster setting, attempts to restructure health services are fraught with pitfalls that often are unanticipated because of inadequate preliminary assessments. A multimodal assessment involving quantitative and qualitative methodologies may provide a more robust mechanism to identify key programmatic priorities and critical barriers for appropriate and sustainable health-system interventions. The purpose of this study is to describe a multimodal assessment using primary healthcare in post-conflict Serbia as a model. METHODS: Integrated quantitative and qualitative methodologies--system characterization and observation, focus group discussions, free-response questionnaires, and Q-methodology--were used to identify needs, problems, and potential barriers to primary healthcare development in Serbia. Participants included primary healthcare providers and administrators from 13 institutions throughout Belgrade. RESULTS: Demographic data indicate a well-established infrastructure of primary health centers and stations. However, focus group discussions and free-response questionnaires reveal significant impediments to delivery of care: (1) Inadequate equipment, supplies, and medications; (2) Poor financial investment; (3) Discouraging worker salaries; (4) Few opportunities for professional development; and (5) Little emphasis on or respect for primary healthcare. Q-methodology of provider perceptions and opinions supports these concerns, shows remarkable consensus among participants, and provides further insights toward system development by grouping respondents into distinctive types. CONCLUSIONS: This study identified the critical needs and barriers to development of primary healthcare in Serbia. This combined methodology may serve as a model for future health system assessments in the post-conflict and post-disaster settings.

Delivery of Health Care↗

Application of magnetic resonance imaging to study pathophysiology in brain disease models.

Magnetic resonance imaging (MRI) provides a noninvasive and multimodal tool to study neurological disorders in experimental models. MRI experiments can be sensitized to various contrast parameters and, hence, enable comprehensive assessment of normal and abnormal brain physiology. Different conventional and novel MRI techniques have been developed that supply specific information on lesion location and size (e.g., T2- and diffusion-weighted MRI), alterations in tissue structure (e.g., magnetization transfer imaging and diffusion tensor imaging), perfusion deficits (perfusion MRI), brain activation (functional MRI), cell migration (cellular MRI), gene expression (molecular MRI), and more. The advantages of in vivo, longitudinal, and multiparametric studies with MRI provide unique opportunities for characterizing and delineating experimental models of neurological diseases and pathophysiological mechanisms, as well as spontaneous and treatment-induced recovery mechanisms.

Animals↗

Model-based imaging.

The concept of model-based imaging provides a possibility of integration of both structural and functional information obtained by imaging and nonimaging sources of diagnostically relevant information. Merging information of different origin and nature in a simulated computer patient-specific three-dimensional (3-D) model is important for multimodal imaging approaches to medical diagnostics. The work of F. L. Lizzi on life-like imaging done nearly 20 years ago was the first successful attempt of patient-specific 3-D computer modeling using conventional ultrasonography data. He demonstrated the applications of such 3-D models, which incorporated acoustic, optical and thermal properties of imaged tissue, in physiologic studies, in planning and monitoring ultrasonic hyperthermia and ablation. However, numerous obstacles hinder the wide use of the model-based imaging concept. Using the example of model-based imaging of prostate, the advantages and limitation on the applicability of the concept are discussed. Attempts of implementing the model-based imaging concept in the mechanical imaging technology--imaging with the use of measurements of stress pattern on the surface of tissue--are described. It is shown that composing a patient-specific 3-D model requires well-defined and carefully validated algorithms for translating features of the object assessed by an imaging modality into the quantitative anatomic and histopathologic parameters.

Algorithms↗

Multimodality imaging for vertebral metastases in a rat osteolytic model.

Imaging modalities facilitate the detection of early bony metastases. Few studies specifically address vertebral metastases in animal models for preclinical (early, asymptomatic) disease. We performed intracardiac injection of human breast cancer (MT-1) cells in 35 athymic nude rats. We evaluated potential temporal differences in appendicular versus axial metastases as detectable by longitudinal in vivo conventional radiography (ie, fine detail radiography and two-dimensional fluoroscopy). We compared bioluminescent reporter imaging with conventional radiographs in the detection of vertebral metastasis, and compared bioluminescent imaging with subsequent ex vivo microcomputed tomography analysis of osteolysis. The mean survival was 25 days in the animals that had metastases develop. Conventional radiographs identified appendicular osteolysis by 14 days; however, vertebral osteolysis was identified late in the metastatic spread (Days 25-28). Bioluminescence imaging was more sensitive in earlier detection of vertebral lesions in all imaged animals at Day 21, which corresponded to microcomputed tomography evaluation of osteolysis. Conventional radiographs do not appear useful for early detection of vertebral metastasis. Early identification of metastasis is important when considering the use of this model to evaluate therapeutic outcomes directed toward vertebral metastasis.

Animals↗

Locally linear discriminant analysis for multimodally distributed classes for face recognition with a single model image.

We present a novel method of nonlinear discriminant analysis involving a set of locally linear transformations called "Locally Linear Discriminant Analysis (LLDA)." The underlying idea is that global nonlinear data structures are locally linear and local structures can be linearly aligned. Input vectors are projected into each local feature space by linear transformations found to yield locally linearly transformed classes that maximize the between-class covariance while minimizing the within-class covariance. In face recognition, linear discriminant analysis (LDA) has been widely adopted owing to its efficiency, but it does not capture nonlinear manifolds of faces which exhibit pose variations. Conventional nonlinear classification methods based on kernels such as generalized discriminant analysis (GDA) and support vector machine (SVM) have been developed to overcome the shortcomings of the linear method, but they have the drawback of high computational cost of classification and overfitting. Our method is for multiclass nonlinear discrimination and it is computationally highly efficient as compared to GDA. The method does not suffer from overfitting by virtue of the linear base structure of the solution. A novel gradient-based learning algorithm is proposed for finding the optimal set of local linear bases. The optimization does not exhibit a local-maxima problem. The transformation functions facilitate robust face recognition in a low-dimensional subspace, under pose variations, using a single model image. The classification results are given for both synthetic and real face data.

Algorithms↗

Generic model for the localization of the cerebral cortex and preoperative multimodal integration in epilepsy surgery.

In cerebral cortex neurosurgery and particularly in epilepsy surgery, the recognition of individual cortical anatomic landmarks is necessary for presurgical evaluation and planning. To overcome the classical great variability in the superficial aspect of the human cerebral cortex, we have developed an original generic description of the cerebral cortex in a three-dimensional structure. The result is a generic model matching the cortical topography of each brain regardless of inter- and intra-individual variability. In this model, sulcal roots (fundi) are separated by more or less superficial annectent gyrus, and buried by operculization during the gyrification. This original generic model of the cerebral cortex enabled us to develop a mathematical methodology for the construction of a structural representation of the cortical topography from a T1-weighted three-dimensional MR image. This program can provide automatic detection and recognition of the main cortical sulci.

Algorithms↗

A mixture model for bovine abortion and foetal survival.

The effect of spontaneous abortion on the dairy industry is substantial, costing the industry on the order of US dollars 200 million per year in California alone. We analyse data from a cohort study of nine dairy herds in Central California. A key feature of the analysis is the observation that only a relatively small proportion of cows will abort (around 10;15 per cent), so that it is inappropriate to analyse the time-to-abortion (TTA) data as if it were standard censored survival data, with cows that fail to abort by the end of the study treated as censored observations. We thus broaden the scope to consider the analysis of foetal lifetime distribution (FLD) data for the cows, with the dual goals of characterizing the effects of various risk factors on (i). the likelihood of abortion and, conditional on abortion status, on (ii). the risk of early versus late abortion. A single model is developed to accomplish both goals with two sets of specific herd effects modelled as random effects. Because multimodal foetal hazard functions are expected for the TTA data, both a parametric mixture model and a non-parametric model are developed. Furthermore, the two sets of analyses are linked because of anticipated dependence between the random herd effects. All modelling and inferences are accomplished using modern Bayesian methods.

Abortion, Veterinary↗

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology↗

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

Preoperative radiochemotherapy and radical resection for stages II to IV oral and oropharyngeal cancer: grade of regression as crucial prognostic factor.

The purpose of this study was to assess the prognostic value of histological response to preoperative radiochemotherapy in an established multimodal therapy concept for advanced oral and oropharyngeal cancer. Two hundred and twenty-two patients who underwent preoperative radiochemotherapy (RCT: 50 Gy, mitomycin C and fluorouracil) and radical surgery were retrospectively evaluated. Resected tumours of all patients were histologically analysed and response to RCT was classified in histopathological grades of regression (RG). In a multivariate statistical analysis, RG was compared with established factors regarding their predictive value for overall and disease-specific survival. The 5-year overall survival probability in the different groups of histopathological regression grades were: RG1 (no vital tumour): 73.4%, RG2 (minimal tumour remnants encompassing less than 5%): 72.1%, RG3 (5-50% vital tumour cells): 41.9%, RG4 (more than 50% vital tumour): 37.9%. For disease-specific survival probability no significant differences were found between both groups of "responders" (RG1 and RG2) nor between "non-responders" (RG3 and RG4), whereas responders and non-responders differed significantly from each other (log-rank test; p < 0.001). T-classification, N-classification and disease stage, histological grading, tumour site, age, and sex had less prognostic value than RG in a Cox regression model. In the neoadjuvant multimodal therapy concept, histological response to preoperative RCT is a crucial prognostic factor even when surgical R0-resection is accomplished. Thus, non-responders have to be regarded as high-risk patients for recurrence and may benefit from further therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Concepts and models of sleep regulation: an overview.

Various mathematical models have been proposed to account for circadian, ultradian and homeostatic aspects of sleep regulation. Most circadian models assume that multiple oscillators underlie the differences in period and entrainment properties of the sleep/wake cycle and other rhythms (e.g. body temperature). Interactions of the oscillators have been postulated to account for multimodal sleep/wake patterns. The ultradian models simulate the cyclic alternation of nonREM sleep and REM sleep by assuming a reciprocal interaction of two cell groups. The homeostatic models propose that a sleep/wake dependent process (Process S) underlies the rise in sleep pressure during waking and its decay during sleep. The time course of this process has been derived from EEG slow-wave activity, an indicator of nonREM sleep intensity. The predictions of homeostatic models have been most extensively tested in experiments. The interaction of Process S with a single circadian process can account for multimodal sleep/wake patterns, internal desynchronization and the time course of daytime sleepiness. Close links have emerged between the processes postulated by the various models and specific brain mechanisms. Due to its recent quantitative elaboration and experimental validation, the modelling approach has become one of the potent research strategies in sleep science.

Journal Article↗