Significant differences in the caecal bacterial microbiota of red and grey squirrels in Britain.

Introduction. Red squirrel populations have declined in the UK since the introduction of the grey squirrel, due to resource competition and grey squirrels carrying a squirrelpox virus that is fatal to red squirrels.Hypothesis/Gap Statement. It is not known if the gut microbiota of the two species is similar and if this could impact the survival of red squirrels.Aim. The aim of this study was to profile the caecal microbiota of red and grey squirrels obtained opportunistically from a conservation programme in North Wales.Methodology. Bacterial DNA was extracted from ten red and ten grey squirrels and sent for 16S rRNA sequencing. Three samples from red squirrels returned less than 5000 reads, and so were not carried forward for further analyses.Results. Samples taken from the caeca of red squirrels had significantly lower bacterial diversity and a higher percentage of Bacilli bacteria when compared to samples from grey squirrels. When the abundance of bacterial groups across all levels of phylogenetic classifications was compared between the two groups of squirrels, grey squirrels had a higher abundance of bacteria belonging to the families S24-7, RF39 and Rikenellaceae. Escherichia coli with resistance to amoxicillin/clavulanic acid was identified in all samples. Cefotaxime resistance was identified in two samples from grey squirrels along with sulfamethoxazole/trimethoprim in one of these samples.Conclusion. Clear differences between the caecal microbiota of the two species of squirrel were identified, which could potentially impact their overall health and ability to compete for resources.

Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study.

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.

Mid-Activity and At-Home Wearable Bioimpedance Elucidates an Interpretable Digital Biomarker of Muscle Fatigue.

OBJECTIVE: Muscle health and decreased muscle performance (fatigue) quantification has proven to be an invaluable tool for both athletic performance assessment and injury prevention. However, existing methods estimating muscle fatigue are infeasible for everyday use. Wearable technologies are feasible for everyday use and can enable discovery of digital biomarkers of muscle fatigue. Unfortunately, the current state-of-the-art wearable systems for muscle fatigue tracking suffer from either low specificity or poor usability. METHODS: We propose using dual-frequency bioimpedance analysis (DFBIA) to non-invasively assess intramuscular fluid dynamics and thereby muscle fatigue. A wearable DFBIA system was developed to measure leg muscle fatigue of 11 individuals during a 13-day protocol consisting of exercise and unsupervised at-home portions. RESULTS: We derived a digital biomarker of muscle fatigue, fatigue score, from the DFBIA signals that was able to estimate the percent reduction in muscle force during exercise with repeated-measures Pearson's r = 0.90 and mean absolute error (MAE) of 3.6%. This fatigue score also estimated delayed onset muscle soreness with repeated-measures Pearson's r = 0.83 and MAE = 0.83. Using at-home data, DFBIA was strongly associated with absolute muscle force of participants (n = 198, p < 0.001). CONCLUSION: These results demonstrate the utility of wearable DFBIA for non-invasively estimating muscle force and pain through the changes in intramuscular fluid dynamics. SIGNIFICANCE: The presented approach may inform development of future wearable systems for quantifying muscle health and provide a novel framework for athletic performance optimization and injury prevention.

Validating Adhesive-Free Bioimpedance of the Leg in Mid-Activity and Uncontrolled Settings.

OBJECTIVE: Musculoskeletal health monitoring is limited in everyday settings where patient symptoms can substantially change - delaying treatment and worsening patient outcomes. Wearable technologies aim to quantify musculoskeletal health outside clinical settings but sensor constraints limit usability. Wearable localized multi-frequency bioimpedance assessment (MFBIA) shows promise for tracking musculoskeletal health but relies on gel electrodes, hindering extended at-home use. Here, we address this need for usable technologies for at-home musculoskeletal health assessment by designing a wearable adhesive-free MFBIA system using textile electrodes in extended uncontrolled mid-activity settings. METHODS: An adhesive-free multimodal wearable leg MFBIA system was developed in-lab under realistic conditions (5 participants, 45 measurements). Mid-activity textile and gel electrode MFBIA was compared across multiple compound movements (10 participants). Accuracy in tracking long-term changes in leg MFBIA was assessed by correlating gel and textile MFBIA simultaneously recorded in uncontrolled settings (10 participants, 80+ measurement hours). RESULTS: Mid-activity MFBIA measurements with textile electrodes agreed highly with (ground truth) gel electrode measurements (average [Formula: see text], featuring <1-Ohm differences (0.618 ± 0.340 Ω) across all movements. Longitudinal MFBIA changes were successfully measured in extended at-home settings (repeated measures r = 0.84). Participant responses found the system to be comfortable and intuitive (8.3/10), and all participants were able to don and operate the system independently. CONCLUSION: This work demonstrates wearable textile electrodes can be a viable substitute for gel electrodes when monitoring leg MFBIA in dynamic, uncontrolled settings. SIGNIFICANCE: Adhesive-free MFBIA can improve healthcare by enabling robust wearable musculoskeletal health monitoring in at-home and everyday settings.

Wearable Mid-Activity Measurement of Lower Limb Electrical Bioimpedance Estimates Vertical Ground Reaction Force Features.

In recent years, wearable mid-activity electrical bioimpedance (EBI) sensing has been used to non-invasively track changes in edema and swelling levels within human joints. While the physiological origin of the changes in mid-activity EBI measurements have been demonstrated, EBI waveform patterns during activity have not been explored. In this work, we present a novel approach to extract waveform features from EBI measurements during gait to estimate the changes in vertical ground reaction forces (vGRF) corresponding to fatigue. Wearable EBI and vGRF data were measured from six healthy subjects during an asymmetric fatiguing protocol. For the exercised leg, the first peak of vGRF corresponding to the initial phase of simple support, decreased significantly and the loading rate increased significantly between the beginning and the end of the protocol. No significant change in these parameters were observed for the control leg. The first peak of vGRF and loading rate during the protocol (15 walking sessions) were correlated to the multi-frequency EBI features with mean Pearson's r=0.81 and r=0.777, respectively. The results of this proof-of-concept study demonstrate the feasibility of estimating biomechanical parameters during activity with wearable EBI. Clinical Relevance - The proposed wearable system and associated signal processing could enable convenient tracking of changes in vGRFs during daily living activities, allowing physiotherapists and doctors to remotely monitor the progress and adherence of their patients and thereby reducing the number of clinical visits.

Wearable Seismocardiography-Based Assessment of Stroke Volume in Congenital Heart Disease.

Background Patients with congenital heart disease (CHD) are at risk for the development of low cardiac output and other physiologic derangements, which could be detected early through continuous stroke volume (SV) measurement. Unfortunately, existing SV measurement methods are limited in the clinic because of their invasiveness (eg, thermodilution), location (eg, cardiac magnetic resonance imaging), or unreliability (eg, bioimpedance). Multimodal wearable sensing, leveraging the seismocardiogram, a sternal vibration signal associated with cardiomechanical activity, offers a means to monitoring SV conveniently, affordably, and continuously. However, it has not been evaluated in a population with significant anatomical and physiological differences (ie, children with CHD) or compared against a true gold standard (ie, cardiac magnetic resonance). Here, we present the feasibility of wearable estimation of SV in a diverse CHD population (N=45 patients). Methods and Results We used our chest-worn wearable biosensor to measure baseline ECG and seismocardiogram signals from patients with CHD before and after their routine cardiovascular magnetic resonance imaging, and derived features from the measured signals, predominantly systolic time intervals, to estimate SV using ridge regression. Wearable signal features achieved acceptable SV estimation (28% error with respect to cardiovascular magnetic resonance imaging) in a held-out test set, per cardiac output measurement guidelines, with a root-mean-square error of 11.48 mL and R2 of 0.76. Additionally, we observed that using a combination of electrical and cardiomechanical features surpassed the performance of either modality alone. Conclusions A convenient wearable biosensor that estimates SV enables remote monitoring of cardiac function and may potentially help identify decompensation in patients with CHD.

Helium Plasma-Assisted Breast Reduction: A Pilot Study.

Background: Reduction mammaplasty and mastopexy are currently some of the most performed breast procedures. Techniques typically involve deepithelialization of the nipple-areola complex pedicle. Traditionally, scalpel or scissor dissection is performed below the basal skin layer to remove the germinal epithelium but above the subcutis to preserve the subdermal vascular plexus. Deepithelialization thus leaves a strong dermal "leash" for the pedicle while preserving the subdermal blood supply. This process is time intensive and bloody, and often an assistant is required for countertraction. Previously, authors have described laser-assisted breast reduction surgery as an alternative to traditional cold knife techniques. The advent of helium plasma generators offers another option for deepithelialization. This study is a preliminary assessment of the safety and efficacy of this application. Objectives: The authors performed a prospective pilot study of 10 patients who underwent outpatient, inferior pedicle, breast reduction mammaplasty, or mastopexy surgery by a single surgeon. Outcomes were assessed for safety and efficacy. Representative tissue samples were evaluated by an independent pathology group. Methods: All patients received standard outpatient perioperative care. Deepithelialization was performed using the Renuvion helium plasma device (Apyx Medical, Clearwater, FL), and standard breast reduction or mastopexy was performed. Results: No major complications occurred in our series. Minor complications occurred in 1 patient (10%). No inclusion cysts were recorded in any patients. Conclusions: Helium plasma energy for deepithelialization in breast reduction was found to be safe, efficient, and effective. Decreased operating room time and blood loss suggest that helium plasma is a potential alternative for surgeons who have access to this technology.

Investigations into Salmonella Contamination in Feed Mills Producing Rations for the Broiler Industry in Great Britain.

Feed-associated Salmonella serovars continue to be reported in poultry flocks. A study was conducted to investigate Salmonella contamination in major commercial feed mills that produce rations for broiler chickens within Great Britain. Dust and large moist gauze swab samples (12,791) were collected from 22 feed mills on 31 visits. Salmonella was isolated from 20 mills, with 15 mills (75%) having fewer than 5% Salmonella-positive samples. Fifty-one Salmonella serovars were isolated, with a large proportion of isolates being Salmonella (S.) Kedougou (29.4%) or S. 13,23:i:- (21.4%). European Union-regulated Salmonella serovars (Enteritidis, Infantis, Typhimurium and its monophasic variants) were isolated from 12 mills, mostly from non-processing areas, accounting for 40 isolates (4.4% of all Salmonella-positive samples). Fifteen Salmonella serovars were only isolated once. In terms of individual sampling locations within the mill, the waste handling locations were significantly more likely to be Salmonella-positive than some other mill locations. When sampling locations were grouped, samples collected from finished product areas were significantly less likely to be Salmonella-positive for Salmonella than some other mill areas. In conclusion, this study found that most mills producing broiler rations showed low-level Salmonella contamination.

Observations on the distribution and control of Salmonella in commercial broiler hatcheries in Great Britain.

Salmonella can enter hatcheries via contaminated eggs and other breaches of biosecurity. The study examined the prevalence and distribution of Salmonella in commercial hatcheries and assessed the effects of providing advice on Salmonella control. Intensive swab sampling was performed throughout 23 broiler hatcheries in Great Britain (GB). Swabs were cultured using a modified ISO6579:2017 method. After each visit, tailored advice on biosecurity and cleaning and disinfection procedures was provided to the hatchery managers. Repeat sampling was carried out in 10 of the 23 hatcheries. Salmonella prevalence ranged between 0% and 33.5%, with the chick handling areas, hatcher areas, macerator area, tray wash/storage areas, external areas and other waste handling areas being more contaminated than the setter areas. Salmonella Senftenberg and Salmonella 13,23:i:- were the most commonly isolated serovars. There was a reduction in Salmonella prevalence at the second visit in eight out of 10 premises, but prevalence values had increased again in all of the improved hatcheries that were visited a third time. One hatchery harboured a difficult-to-control resident Salmonella 13,23:i:- strain and was visited six times; by the final visit, Salmonella prevalence was 2.3%, reduced from a high of 23.1%. In conclusion, the study found low-level Salmonella contamination in some GB broiler hatcheries, with certain hatcheries being more severely affected. Furthermore, it was shown that Salmonella typically is difficult to eradicate from contaminated hatcheries, but substantial reductions in prevalence are possible with improvements to biosecurity, cleaning and disinfection.

A Wearable Multimodal Sensing System for Tracking Changes in Pulmonary Fluid Status, Lung Sounds, and Respiratory Markers.

Heart failure (HF) exacerbations, characterized by pulmonary congestion and breathlessness, require frequent hospitalizations, often resulting in poor outcomes. Current methods for tracking lung fluid and respiratory distress are unable to produce continuous, holistic measures of cardiopulmonary health. We present a multimodal sensing system that captures bioimpedance spectroscopy (BIS), multi-channel lung sounds from four contact microphones, multi-frequency impedance pneumography (IP), temperature, and kinematics to track changes in cardiopulmonary status. We first validated the system on healthy subjects (n = 10) and then conducted a feasibility study on patients (n = 14) with HF in clinical settings. Three measurements were taken throughout the course of hospitalization, and parameters relevant to lung fluid status-the ratio of the resistances at 5 kHz to those at 150 kHz (K)-and respiratory timings (e.g., respiratory rate) were extracted. We found a statistically significant increase in K (p < 0.05) from admission to discharge and observed respiratory timings in physiologically plausible ranges. The IP-derived respiratory signals and lung sounds were sensitive enough to detect abnormal respiratory patterns (Cheyne-Stokes) and inspiratory crackles from patient recordings, respectively. We demonstrated that the proposed system is suitable for detecting changes in pulmonary fluid status and capturing high-quality respiratory signals and lung sounds in a clinical setting.

Forensic soil provenancing in an urban/suburban setting: A simultaneous multivariate approach.

Soil is a ubiquitous material at the Earth's surface with potential to be a useful evidence class in forensic and intelligence applications. Compositional data from a soil survey over North Canberra, Australian Capital Territory, are used to develop and test an empirical soil provenancing method. Mineralogical data from Fourier Transform InfraRed spectroscopy (FTIR) and geochemical data from X-Ray Fluorescence (XRF; for total major oxides) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS; for both total and aqua regia-soluble trace elements) are obtained from the survey's 268 topsoil samples (0-5 cm depth; 1 sample per km2 ). The simultaneous provenancing approach is underpinned by (i) the calculation of Spearman's correlation coefficients (rS ) between an evidentiary sample and all the samples in the database for all variables generated by each analytical method; and (ii) the preparation of an interpolated raster grid of rS for each evidentiary sample and method resulting in a series of provenance rasters ("heat maps"). The simultaneous provenancing method is tested on the North Canberra soil survey with three "blind" samples representing simulated evidentiary samples. Performance metrics of precision and accuracy indicate that the FTIR (mineralogy) and XRF (geochemistry) analytical methods offer the most precise and accurate provenance predictions. Maximizing the number of analytes/analytical techniques is advantageous in soil provenancing. Despite acknowledged limitations, it is concluded that the empirical soil provenancing approach can play an important role in forensic and intelligence applications.

An Integrated Multimodal Knee Brace Enabling Mid-Activity Tracking for Joint Health Assessment.

Developments in wearable technologies created opportunities for non-invasive joint health assessment while subjects perform daily activities during rehabilitation and recovery. However, existing state-of-art solutions still require a health professional or a researcher to set up the device, and most of them are not convenient for at-home use. In this paper, we demonstrate the latest version of the multimodal knee brace that our lab previously developed. This knee brace utilizes four sensing modalities: joint acoustic emissions (JAEs), electrical bioimpedance (EBI), activity and temperature. We designed custom printed-circuit boards and developed firmware to acquire high quality data. For the brace material, we used a commercial knee brace and modified it for the comfort of patients as well as to secure all electrical connections. We updated the electronics to enable rapid EBI measurements for mid-activity tracking. The performance of the multimodal knee brace was evaluated through a proof-of-concept human subjects study (n=9) with 2 days of measurement and 3 sessions per day. We obtained consistent EBI data with less than 1 Ω variance in measured impedance within six full frequency sweeps (each sweep is from 5 kHz to 100 kHz with 256 frequency steps) from each subject. Then, we asked subjects to perform 10 unloaded knee flexion/extensions, while we measured continuous 5 kHz and 100 kHz EBI at every 100 ms. The ratio of the range of reactance (ΔX5kHz/ΔX100kHz) was found to be less than 1 for all subjects for all cycles, which indicates lack of swelling and thereby a healthy joint. We also conducted intra and inter session reliability analysis for JAE recordings through intraclass correlation analysis (ICC), and obtained excellent ICC values (>0.75), suggesting reliable performance on JAE measurements. The presented knee brace could readily be used at home in future work for knee health monitoring of patients undergoing rehabilitation or recovery.

Forensic soil provenancing in an urban/suburban setting: A sequential multivariate approach.

Compositional data from a soil survey over North Canberra, Australian Capital Territory, are used to develop and test an empirical soil provenancing method. Mineralogical data from Fourier transform infrared spectroscopy (FTIR) and magnetic susceptibility (MS), and geochemical data from X-ray fluorescence (XRF; for total major oxides) and inductively coupled plasma-mass spectrometry (ICP-MS; for both total and aqua regia-soluble trace elements) are performed on the survey's 268 topsoil samples (0-5 cm depth; 1 sample per km2 ). Principal components (PCs) are calculated after imputation of censored data and centered log-ratio transformation. The sequential provenancing approach is underpinned by (i) the preparation of interpolated raster grids of the soil properties (including PCs); (ii) the explicit quantification and propagation of uncertainty; (iii) the intersection of the soil property rasters with the values of the evidentiary sample (± uncertainty); and (iv) the computation of cumulative provenance rasters ("heat maps") for the various analytical techniques. The sequential provenancing method is tested on the North Canberra soil survey with three "blind" samples representing simulated evidentiary samples. Performance metrics of precision and accuracy indicate that the FTIR and MS (mineralogy), as well as XRF and total ICP-MS (geochemistry) analytical methods, offer the most precise and accurate provenance predictions. Inclusion of PCs in provenancing adds marginally to the performance. Maximizing the number of analytes/analytical techniques is advantageous in soil provenancing. Despite acknowledged limitations and gaps, it is concluded that the empirical soil provenancing approach can play an important role in forensic and intelligence applications.

Could congressionally mandated incentives lead to deployment of large-scale CO2 capture, facilities for enhanced oil recovery CO2 markets and geologic CO2 storage?

In passing the Bipartisan Budget Act of 2018, Congress reformed and strengthened a section of the tax code, 45Q, which provides tax credits of up to $35/ton CO2 for the capture and utilization of CO2 in qualifying applications such as enhanced oil recovery (EOR) and up to $50/ton CO2 for CO2 that is captured and permanently stored in a geologic repository. Earlier versions of the tax credit with lower credit values generated limited interest. This change to the tax code could potentially alter U.S. energy systems. This paper examines the effect of the increased 45Q credits on CO2 capture, utilization and storage (CCUS) deployment in the United States and on petroleum and power production. A range of potential outcomes is explored using five modeling tools. The paper goes on to explore the potential impact of possible modifications of the current tax credit including extension of its availability in time, the period over which 45Q tax credits can be utilized for any given asset and increases in the value of the credit as well as interactions with technology availability and carbon taxation. The paper concludes that 45Q tax credits could stimulate additional CCUS beyond that which is already underway.

Circulating biomarkers of left ventricular hypertrophy in pediatric coarctation of the aorta.

OBJECTIVE: Patients undergoing surgical repair of aortic coarctation have a 50% risk of pathologic left ventricular remodeling (increased left ventricular mass or relative wall thickness). Endothelin 1, ST2, galectin 3, norepinephrine and B-natriuretic peptide are biomarkers that have been associated with pathologic LV change in adult populations but their predictive value following pediatric coarctation repair are not known. HYPOTHESIS: Biomarker levels at coarctation repair will predict persistent left ventricular remodeling at 1-year follow up. DESIGN: Prospective, cohort study of 27 patients' age 2 days-12 years with coarctation of the aorta undergoing surgical repair. Echocardiograms were performed preoperation, postoperation, and at 1-year follow-up. Plasma biomarker levels were measured at the peri-operative time points. Association between biomarker concentrations and echocardiographic parameters was assessed. RESULTS: Neither left ventricular mass index nor relative wall thickness varied from pre-op to post-op. At pre-op, relative wall thickness was elevated in 52% and left ventricular mass index was elevated in 22%; at follow-up, relative wall thickness was elevated in 13% and left ventricular mass index was elevated in 8%. Presence of residual coarctation did not predict left ventricular remodeling (AUC 0.59; P > .05). Multivariable receiver operating characteristic curve combining pre-op ST2 and endothelin 1 demonstrated significant predictive ability for late pathologic left ventricular remodeling (AUC 0.85; P = .02). CONCLUSIONS: Persistent left ventricular hypertrophy and abnormal relative wall thickness at intermediate-term follow-up was rare compared to previous studies. A model combining pre-op endothelin 1 and ST2 level demonstrated reasonable accuracy at predicting persistent abnormalities in this cohort. Larger studies will be needed to validate this finding and further explore the mechanism of persistent left ventricular remodeling in this population.

Intraprocedural predictors of post-stent retriever thrombectomy subarachnoid hemorrhage in middle cerebral artery stroke.

BACKGROUND: Stent retriever thrombectomy (SRT) in acute thromboembolic stroke can result in post-thrombectomy subarachnoid hemorrhage (PTSAH). Intraprocedural findings associated with PTSAH are not well defined. OBJECTIVE: To identify angiographic findings and procedural factors during SRT that are associated with PTSAH. MATERIALS AND METHODS: This was a retrospective, observational cohort study of consecutive patients with middle cerebral artery (MCA) acute ischemic stroke treated with SRT. Inclusion criteria were: (1) age ≥18 years; (2) thromboembolic occlusion of the MCA; (3) at least one stent retriever pass beginning in an M2 branch; (4) postprocedural CT or MRI scan within 24 hours; (5) non-enhanced CT Alberta Stroke Program Early CT Score >5. Exclusion criteria included multi-territory stroke before SRT. RESULTS: Eighty-five patients were enrolled; eight patients had PTSAH (group 1) and 77 did not (group 2). Baseline demographic and clinical characteristics were comparable between the two groups. In group 1, a significantly greater proportion of patients had more than two stent retriever passes (62.5% vs 18.2%, P=0.01), a stent retriever positioned ≥2 cm along an M2 branch (100% vs 30.2%, P=0.002), and the presence of severe iatrogenic vasospasm before SRT pass (37.5% vs 5.2%, P=0.02). One patient with PTSAH and associated mass effect deteriorated clinically. CONCLUSIONS: An increased number of stent retriever passes, distal device positioning, and presence of severe vasospasm were associated with PTSAH. Neurological deterioration with PTSAH can occur.

Outstanding contribution to pediatric anesthesiology: An interview with Dr. Robert H. Friesen.

Dr. Robert H. Friesen, (1946-) Professor of Anesthesiology, Children's Hospital Colorado, University of Colorado, Anschutz Medical Campus, has played a pivotal and pioneering role in the development of pediatric and congenital cardiac anesthesiology. His transformative research included the study of the hemodynamic effects of inhalational and intravenous anesthetic agents in the newborn and the effects of anesthetic agents on pulmonary vascular resistance in patients with pulmonary hypertension. As a model clinician-scientist, educator, and administrator, he changed the practice of pediatric anesthesia and shaped the careers of hundreds of physicians-in-training, imbuing them with his core values of honesty, integrity, and responsibility. Based on a series of interviews with Dr. Friesen, this article reviews a career that advanced pediatric and congenital cardiac anesthesia during the formative years of the specialties.

Endothelin-1 activation in pediatric patients undergoing surgical coarctation of the aorta repair.

AIM: To determine endothelin-1 (ET-1) concentration before and after surgical coarctectomy and evaluate its association with left ventricular geometric change. METHODS: A prospective, cohort study of 24 patients aged 2 d to 10 years with coarctation of the aorta undergoing surgical repair. A sub-cohort of patients with age < 1 mo was classified as "neonates". Echocardiograms were performed just prior to surgery and in the immediate post-op period to assess left ventricle mass index and relative wall thickness (RWT). Plasma ET-1 levels were assessed at both time points. Association between ET-1 levels and ventricular remodeling was assessed. RESULTS: Patients < 1 year demonstrated higher pre-op ET-1 than post-op (2.8 pg/mL vs 1.9 pg/mL, P = 0.02). Conversely, patients > 1 year had no change in ET-1 concentration before and after surgery (1.1 vs 1.4, NS). Pre-op, patients < 1 year demonstrated significantly higher ET-1 than older children (2.8 vs 1.1, P = 0.001). Post-op there was no difference between the age groups (1.9 vs 1.4, NS). Neither RWT nor left ventricle mass index (LVMI) varied from pre-op to post-op. The subset of neonates showed a strong positive correlation between pre-op ET-1 and RWT (r = 0.92, P = 0.001). Patients with ET-1 > 2 pg/mL pre-op demonstrated higher LVMI (65.7 g/m2.7vs 38.5 g/m2.7, P = 0.004) and a trend towards higher RWT (45% vs 39%, P = 0.07) prior to repair than those with lower ET-1 concentration. CONCLUSION: ET-1 concentration is significantly variable in the peri-operative period surrounding coarctectomy. Older children and infants have different responses to surgical repair suggesting different mechanisms of activation.

Hemodynamic response to ketamine in children with pulmonary hypertension.

BACKGROUND: The safety of ketamine in children with pulmonary hypertension has been debated because of conflicting results of prior studies in which changes in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) have been widely variable. The goal of this prospective study was to quantitate the effects of ketamine on pulmonary hemodynamics in a cohort of children with pulmonary hypertension under conditions in which variables such as airway/ventilatory management, FiO(2), and use of vasodilating anesthetics were controlled. METHODS: The IRB approved this study of 34 children undergoing cardiac catheterization for pulmonary hypertension studies. Following anesthetic induction with sevoflurane and tracheal intubation facilitated by the administration of rocuronium 0.7-1 mg·kg(-1) iv, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg·kg(-1) iv (or 0.5 mg·kg(-1) po preoperatively) and remifentanil iv infusion 0.5-0.7 mcg·kg(-1) ·min(-1). Ventilation was mechanically controlled to maintain PaCO(2) 35-40 mmHg. When endtidal sevoflurane was 0% and FiO(2) was 0.21, baseline heart rate (HR), mean arterial pressure (MAP), mPAP, right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic pressure (RVEDP), cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance (SVRI), indexed pulmonary vascular resistance (PVRI), and cardiac index (CI) were calculated. Each child then received a bolus of ketamine 2 mg·kg(-1) infused over 2 min. Measurements and calculations were repeated 2 min after the conclusion of the infusion. RESULTS: The mean (95% CI) increase in mPAP following ketamine was 2 mmHg (0.2, 3.7), which was statistically significant but clinically insignificant. PVRI and PVRI/SVRI did not change significantly. Hemodynamic changes did not differ among subjects with differing severity of pulmonary hypertension or between subjects chronically treated with pulmonary vasodilators or not. CONCLUSION: Ketamine is associated with minimal, clinically insignificant hemodynamic changes in sedated, mechanically ventilated children with pulmonary hypertension.