scholarly journals Creation and application of virtual patient cohorts of heart models

2020 ◽  
Vol 378 (2173) ◽  
pp. 20190558 ◽  
Author(s):  
S. A. Niederer ◽  
Y. Aboelkassem ◽  
C. D. Cantwell ◽  
C. Corrado ◽  
S. Coveney ◽  
...  
Keyword(s):  
State Of The Art ◽  
Clinical Care ◽  
Virtual Patient ◽  
Patient Specific ◽  
Theme Issue ◽  
Large Numbers ◽  
Cardiac Modelling ◽  
Cardiac Models ◽  
The Individual ◽  
Cardiovascular Modelling

Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

scholarly journals Personalized mathematical oncology: Challenges and opportunities

2021 ◽  
Author(s):  
Michael C. Luo ◽  
Elpiniki Nikolopoulou ◽  
Jana Gevertz
Keyword(s):  
Treatment Response ◽  
Clinical Care ◽  
Population Level ◽  
Personalized Treatment ◽  
Patient Specific ◽  
Individual Treatment ◽  
Specific Data ◽  
Level Statistics ◽  
Challenges And Opportunities ◽  
The Individual

An outstanding challenge in the clinical care of cancer is moving from a one-size-fits-all approach that relies on population-level statistics towards personalized therapeutic design. Mathematical modeling is a powerful tool in treatment personalization, as it allows for the incorporation of patient-specific data so that treatment can be tailor-designed to the individual. In this work, we employ two fitting methodologies to personalize treatment in a mathematical model of murine cancer immunotherapy. Unexpectedly, we found that the predicted personalized treatment response is sensitive to the fitting methodology utilized. This raises concerns about the ability of mathematical models, even relatively simple ones, to make reliable predictions about individual treatment response. Our analyses shed light onto why it can be challenging to make personalized treatment recommendations from a model, but also suggest ways we can increase our confidence in personalized mathematical predictions.

Critical Technical Issues in High Voltage SiC Power Devices

2008 ◽  
Vol 600-603 ◽  
pp. 895-900 ◽  
Author(s):  
Anant K. Agarwal ◽  
Albert A. Burk ◽  
Robert Callanan ◽  
Craig Capell ◽  
Mrinal K. Das ◽  
...  
Keyword(s):  
Threshold Voltage ◽  
Carrier Mobility ◽  
Negative Charge ◽  
State Of The Art ◽  
Power Devices ◽  
Power Mosfets ◽  
Large Numbers ◽  
Technical Issues ◽  
The Difference ◽  
Difficult Issue

In this paper, we review the state of the art of SiC switches and the technical issues which remain. Specifically, we will review the progress and remaining challenges associated with SiC power MOSFETs and BJTs. The most difficult issue when fabricating MOSFETs has been an excessive variation in threshold voltage from batch to batch. This difficulty arises due to the fact that the threshold voltage is determined by the difference between two large numbers, namely, a large fixed oxide charge and a large negative charge in the interface traps. There may also be some significant charge captured in the bulk traps in SiC and SiO2. The effect of recombination-induced stacking faults (SFs) on majority carrier mobility has been confirmed with 10 kV Merged PN Schottky (MPS) diodes and MOSFETs. The same SFs have been found to be responsible for degradation of BJTs.

Quality of Life for Children with Persistent Sinonasal Symptoms

2003 ◽  
Vol 128 (1) ◽  
pp. 17-26 ◽  
Author(s):  
David J. Kay ◽  
Richard M. Rosenfeld
Keyword(s):  
Quality Of Life ◽  
Clinical Care ◽  
Longitudinal Change ◽  
Good Test ◽  
Routine Clinical Care ◽  
Before And After ◽  
The Mean ◽  
The Individual ◽  
Sinonasal Symptoms

OBJECTIVE: The goal was to validate the SN-5 survey as a measure of longitudinal change in health-related quality of life (HRQoL) for children with persistent sinonasal symptoms. DESIGN AND SETTING: We conducted a before and after study of 85 children aged 2 to 12 years in a metropolitan pediatric otolaryngology practice. Caregivers completed the SN-5 survey at entry and at least 4 weeks later. The survey included 5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations. RESULTS: Good test-retest reliability ( R = 0.70) was obtained for the overall SN-5 score and the individual survey items ( R ≥ 0.58). The mean baseline SN-5 score was 3.8 (SD, 1.0) of a maximum of 7.0, with higher scores indicating poorer HRQoL. All SN-5 items had adequate correlation ( R ≥ 0.36) with external constructs. The mean change in SN-5 score after routine clinical care was 0.88 (SD, 1.19) with an effect size of 0.74 indicating good responsiveness to longitudinal change. The change scores correlated appropriately with changes in related external constructs ( R ≥ 0.42). CONCLUSIONS: The SN-5 is a valid, reliable, and responsive measure of HRQoL for children with persistent sinonasal symptoms, suitable for use in outcomes studies and routine clinical care.

scholarly journals Fully Data-Driven Pseudohealthy Synthesis for Planning Valve-Sparing Aortic Root Reconstruction using Conditional Variational Autoencoders

2020 ◽  
Vol 6 (3) ◽  
pp. 284-287
Author(s):  
Jannis Hagenah ◽  
Mohamad Mehdi ◽  
Floris Ernst
Keyword(s):  
Aortic Root ◽  
Similarity Index ◽  
Ground Truth ◽  
Representation Learning ◽  
Patient Specific ◽  
Ultrasound Images ◽  
Specific Geometry ◽  
The Individual ◽  
Native Root ◽  
Original Information

AbstractAortic root aneurysm is treated by replacing the dilated root by a grafted prosthesis which mimics the native root morphology of the individual patient. The challenge in predicting the optimal prosthesis size rises from the highly patient-specific geometry as well as the absence of the original information on the healthy root. Therefore, the estimation is only possible based on the available pathological data. In this paper, we show that representation learning with Conditional Variational Autoencoders is capable of turning the distorted geometry of the aortic root into smoother shapes while the information on the individual anatomy is preserved. We evaluated this method using ultrasound images of the porcine aortic root alongside their labels. The observed results show highly realistic resemblance in shape and size to the ground truth images. Furthermore, the similarity index has noticeably improved compared to the pathological images. This provides a promising technique in planning individual aortic root replacement.

scholarly journals Considerations for the Management of Women with Breast Cancer during the COVID-19 Pandemic

2020 ◽  
Vol 5 (03) ◽  
pp. 260-263
Author(s):  
Monica Irukulla ◽  
Palwai Vinitha Reddy
Keyword(s):  
Breast Cancer ◽  
Resource Allocation ◽  
Patient Care ◽  
Cancer Patients ◽  
Cancer Care ◽  
Clinical Care ◽  
Current Availability ◽  
The Individual

AbstractOutcomes in cancer patients are strongly influenced by timeliness and quality of multidisciplinary interventions. The COVID-19 pandemic has led to severe disruption in cancer care in many countries. This has necessitated several changes in clinical care and workflow, including resource allocation, team segregation and deferment of many elective procedures. Several international oncological societies have proposed guidelines for the care of patients afflicted with breast cancer during the pandemic with a view to optimize resource allocation and maximize risk versus benefit for the individual and society. Clinicians may utilize these recommendations to adapt patient care, based on the current availability of resources and severity of the COVID-19 pandemic in each region. This article discusses the guidelines for care of patients afflicted with breast cancer during the pandemic.

scholarly journals Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xudong Zhu ◽  
Zhiyang Chen ◽  
Weiyan Shen ◽  
Gang Huang ◽  
John M. Sedivy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
State Of The Art ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Cell Fate Decision ◽  
The Past ◽  
Fate Decision ◽  
The Individual ◽  
Remarkable Progress

AbstractRemarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

scholarly journals Introduction to redundancy rules: the continuous wavelet transform comes of age

2018 ◽  
Vol 376 (2126) ◽  
pp. 20170258 ◽  
Author(s):  
Paul S. Addison
Keyword(s):  
Wavelet Transform ◽  
Continuous Wavelet Transform ◽  
State Of The Art ◽  
Structural Characteristics ◽  
Continuous Wavelet ◽  
Theme Issue ◽  
Current State ◽  
Analysis Methods ◽  
Wide Range ◽  
New Form

Redundancy: it is a word heavy with connotations of lacking usefulness. I often hear that the rationale for not using the continuous wavelet transform (CWT)—even when it appears most appropriate for the problem at hand—is that it is ‘redundant’. Sometimes the conversation ends there, as if self-explanatory. However, in the context of the CWT, ‘redundant’ is not a pejorative term, it simply refers to a less compact form used to represent the information within the signal. The benefit of this new form—the CWT—is that it allows for intricate structural characteristics of the signal information to be made manifest within the transform space, where it can be more amenable to study: resolution over redundancy. Once the signal information is in CWT form, a range of powerful analysis methods can then be employed for its extraction, interpretation and/or manipulation. This theme issue is intended to provide the reader with an overview of the current state of the art of CWT analysis methods from across a wide range of numerate disciplines, including fluid dynamics, structural mechanics, geophysics, medicine, astronomy and finance. This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.

scholarly journals Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Mussap ◽  
Vassilios Fanos
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Wide Range ◽  
Life Threatening ◽  
The Individual ◽  
Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration

2021 ◽  
Vol 376 (1821) ◽  
pp. 20190765 ◽  
Author(s):  
Giovanni Pezzulo ◽  
Joshua LaPalme ◽  
Fallon Durant ◽  
Michael Levin
Keyword(s):  
Large Scale ◽  
Computational Models ◽  
State Of The Art ◽  
Memory Representation ◽  
Theme Issue ◽  
Evolutionary Innovation ◽  
New Interpretation ◽  
The Brain

Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states—in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo . This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

Autonomy and non-autonomy in Drosophila mesoderm determination and morphogenesis

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 853-859 ◽  
Author(s):  
M. Leptin ◽  
S. Roth
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Developmental Program ◽  
Cell Shape Change ◽  
Ventral Furrow ◽  
Large Numbers ◽  
The Individual ◽  
Mutant Cells ◽  
Transplantation Experiments ◽  
Shape Changes

The mesoderm in Drosophila invaginates by a series of characteristic cell shape changes. Mosaics of wild-type cells in an environment of mutant cells incapable of making mesodermal invaginations show that this morphogenetic behaviour does not require interactions between large numbers of cells but that small patches of cells can invaginate independent of their neighbours' behaviour. While the initiation of cell shape change is locally autonomous, the shapes the cells assume are partly determined by the individual cell's environment. Cytoplasmic transplantation experiments show that areas of cells expressing mesodermal genes ectopically at any position in the egg form an invagination. We propose that ventral furrow formation is the consequence of all prospective mesodermal cells independently following their developmental program. Gene expression at the border of the mesoderm is induced by the apposition of mesodermal and non-mesodermal cells.

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