Ex Vivo Working Porcine Heart Model.

Ex vivo working porcine heart models allow for the study of a heart's function and physiology outside the living organism. These models are particularly useful due to the anatomical and physiological similarities between porcine and human hearts, providing an experimental platform to investigate cardiac disease or assess donor heart viability for transplantation. This chapter presents an in-depth discussion of the model's components, including the perfusate, preload, and afterload.

Learning pharmacometric covariate model structures with symbolic regression networks.

Efficiently finding covariate model structures that minimize the need for random effects to describe pharmacological data is challenging. The standard approach focuses on identification of relevant covariates, and present methodology lacks tools for automatic identification of covariate model structures. Although neural networks could potentially be used to approximate covariate-parameter relationships, such approximations are not human-readable and come at the risk of poor generalizability due to high model complexity.

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results.

Background: Existing working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control.

Updates on the diagnosis and management of celiac disease.

Celiac disease is a chronic autoimmune enteropathy affecting about 1% of the population. Gluten ingestion triggers an immune response in genetically susceptible patients, resulting in intestinal and extraintestinal disease manifestations. Current recommendations for diagnosis include serology for celiac-specific antibodies to transglutaminase, endomysium, and deamidated gliadin, and IgA serology.

Nowcasting (Short-Term Forecasting) of COVID-19 Hospitalizations Using Syndromic Healthcare Data, Sweden, 2020.

We report on local nowcasting (short-term forecasting) of coronavirus disease (COVID-19) hospitalizations based on syndromic (symptom) data recorded in regular healthcare routines in Östergötland County (population ≈465,000), Sweden, early in the pandemic, when broad laboratory testing was unavailable. Daily nowcasts were supplied to the local healthcare management based on analyses of the time lag between telenursing calls with the chief complaints (cough by adult or fever by adult) and COVID-19 hospitalization. The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.

Estimating the SARS-CoV-2 infected population fraction and the infection-to-fatality ratio: a data-driven case study based on Swedish time series data.

We demonstrate that finite impulse response (FIR) models can be applied to analyze the time evolution of an epidemic with its impact on deaths and healthcare strain. Using time series data for COVID-19-related cases, ICU admissions and deaths from Sweden, the FIR model gives a consistent epidemiological trajectory for a simple delta filter function. This results in a consistent scaling between the time series if appropriate time delays are applied and allows the reconstruction of cases for times before July 2020, when RT-PCR testing was not widely available.

Prevention of Ischemic Myocardial Contracture Through Hemodynamically Controlled DCD.

Purpose: Ischemic myocardial contracture (IMC) or "stone heart" is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated upon circulatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC.

Individualized closed-loop anesthesia through patient model partitioning.

Closed-loop controlled drug dosing has the potential of revolutionizing clinical anesthesia. However, inter-patient variability in drug sensitivity poses a central challenge to the synthesis of safe controllers. Identifying a full individual pharmacokinetic-pharmacodynamic (PKPD) model for this synthesis is clinically infeasible due to limited excitation of PKPD dynamics and presence of unmodeled disturbances.

Identifiability issues in estimating the impact of interventions on Covid-19 spread.

The Covid-19 pandemic has spawned numerous dynamic modeling attempts aimed at estimation, prediction, and ultimately control. The predictive power of these attempts has varied, and there remains a lack of consensus regarding the mechanisms of virus spread and the effectiveness of various non-pharmaceutical interventions that have been enforced regionally as well as nationally. Setting out in data available in the spring of 2020, and with a now-famous model by Imperial College researchers as example, we employ an information-theoretical approach to shed light on why the predictive power of early modeling approaches have remained disappointingly poor.

Phase-controlled intermittent intratracheal insufflation of oxygen during chest compression-active decompression mCPR improves coronary perfusion pressure over continuous insufflation.

Purpose: It has previously been shown that continuous intratracheal insufflation of oxygen (CIO) is superior to intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics. The purpose of this study was to investigate gas exchange and haemodynamics with a new technique of phase-controlled intermittent insufflation of oxygen (PIIO) compared to CIO.

Method: Twenty (20) pigs were used, stratified into two groups (CIO, PIIO), with 10 animals each.

Optimizing Robust PID Control of Propofol Anesthesia for Children: Design and Clinical Evaluation.

Objective: The goal of this paper was to optimize robust PID control for propofol anesthesia in children aged 5-10 years to improve performance, particularly to decrease the time of induction of anesthesia while maintaining robustness.

Methods: We analyzed results of a previous study conducted by our group to identify opportunities for system improvement. Allometric scaling was introduced to reduce the interpatient variability and a new robust PID controller was designed using an optimization-based method.

Closed-loop regulation of arterial pressure after acute brain death.

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors.

Closed-Loop Prevention of Hypotension in the Heartbeating Brain-Dead Porcine Model.

Unlabelled: Objective: The purpose of this paper is to demonstrate feasibility of a novel closed-loop controlled therapy for prevention of hypertension in the heartbeating brain-dead porcine model.

Methods: Dynamic modeling and system identification were based on in vivo data. A robust controller design was obtained for the identified models.

Robust closed-loop control of induction and maintenance of propofol anesthesia in children.

Background: During closed-loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index).

Quantification of the variability in response to propofol administration in children.

Closed-loop control of anesthesia is expected to decrease drug dosage and wake up time while increasing patient safety and decreasing the work load of the anesthesiologist. The potential of closed-loop control in anesthesia has been demonstrated in several clinical studies. One of the challenges in the development of a closed-loop system that can be widely accepted by clinicians and regulatory authorities is the effect of interpatient variability in drug sensitivity.

Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection.

Traumatic brain injury (TBI) causes selective hippocampal cell death, which is believed to be associated with cognitive impairment observed both in clinical and experimental settings. Although neurotrophin administration has been tested as a strategy to prevent cell death following TBI, the potential neuroprotective role of neurotrophin-4/5 (NT-4/5) in TBI remains unknown. We hypothesized that NT-4/5 would offer neuroprotection for selectively vulnerable hippocampal neurons following TBI.

Acute, transient hemorrhagic hypotension does not aggravate structural damage or neurologic motor deficits but delays the long-term cognitive recovery following mild to moderate traumatic brain injury.

Objectives: Posttraumatic hypotension is believed to increase morbidity and mortality in traumatically brain-injured patients. Using a clinically relevant model of combined traumatic brain injury with superimposed hemorrhagic hypotension in rats, the present study evaluated whether a reduction in mean arterial blood pressure aggravates regional brain edema formation, regional cell death, and neurologic motor/cognitive deficits associated with traumatic brain injury.

Design: Experimental prospective, randomized study in rodents.

Delayed transplantation of human neurons following brain injury in rats: a long-term graft survival and behavior study.

The NTera2 (NT2) cell line is a homogeneous population of cells, which, when treated in vitro with retinoic acid, terminally differentiate into postmitotic neuronal NT2N cells. Although NT2N neurons transplanted in the acute (24 h postinjury) period survive for up to 1 month following experimental traumatic brain injury (TBI), nothing is known of their ability to survive for longer periods or of their effects when engrafted during the chronic postinjury period. Adult male Sprague-Dawley rats (n = 348; 360-400 g) were initially anesthetized and subjected to severe lateral fluid-percussion (FP) brain injury or sham injury.

Administration of monoclonal antibodies neutralizing the inflammatory mediators tumor necrosis factor alpha and interleukin -6 does not attenuate acute behavioral deficits following experimental traumatic brain injury in the rat.

Purpose: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered intracerebroventricularly (i.c.

Proteins released from degenerating neurons are surrogate markers for acute brain damage.

The experimental and clinical study of degenerative brain disorders would benefit from new surrogate markers for brain damage. To identify novel candidate markers for acute brain injury, we report that rat cortical neurons release over 60 cytoskeletal and other proteins, as well as their proteolytic fragments into the medium during neuronal death. The profiles of released proteins differ for necrosis and apoptosis, although a subset of proteins is released generally during neurodegeneration.

Family physicians' views of the preventive services task force recommendations regarding nutritional counseling.

Objective: To determine the level of agreement between family physicians and the nutritional counseling recommendations of the US Preventive Services Task Force.

Design: A survey was developed, tested, and mailed to a random nationwide sample of 500 family physicians.

Participants: Active members of the American Academy of Family Physicians, Kansas City, Mo.

Perceptions and practices of family physicians regarding diet and cancer.

This study was undertaken to determine the beliefs of family physicians about the role of diet and cancer, as well as to determine how often family physicians assess dietary risks in patient encounters and recommend preventive dietary practices to reduce cancer risk. This study consisted of a survey of a national random sample of 486 family physicians from the American Academy of Family Physicians (AAFP), and 237 responded (49%). The demographic characteristics of the respondents were determined to be similar to those of the AAFP membership.