Multiscale Structure and Function of the Aortic Valve Apparatus.

While studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, herein referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and supporting left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underly the simultaneous fulfilment of these functions. A brief overview of the tools used to investigate the AVA is included, such as: medical imaging modalities, experimental methods, and computational modelling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this paper support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

Ex vivo perfusion of human lymph nodes†.

In a recent study published in The Journal of Pathology, Barrow-McGee et al described a feasibility study of a real-time ex vivo perfusion model of the axillary lymph nodes (ALNs) from breast cancer patients for immune-oncological investigations. The study showed that perfused ALNs remain viable for up to 24 h, and perfusion of therapeutic antibodies confirmed the ability to reach ALN-resident cells. This work is a highly encouraging demonstration of feasibility for further research into lymphatic system function, with applications to immune function, vaccinations, and cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Delayed Achievement of Oral Feedings Is Associated with Adverse Neurodevelopmental Outcomes at 18 to 26 Months Follow-up in Preterm Infants.

OBJECTIVE: This study aimed to compare neurodevelopmental outcomes in preterm infants at 18 to 26 months corrected age (CA) who did versus did not achieve full oral feedings at 40 weeks postmenstrual age (PMA). STUDY DESIGN: This retrospective study included infants born between 2010 and 2015 with gestational age <32 weeks and followed between 18 and 26 months CA. Achievement of full oral feedings was defined as oral intake >130 mL/kg/d for >72 hours by 40 weeks PMA. Incidence of cognitive, language, or motor delay, or cerebral palsy at 18 to 26 months CA was compared in multivariable analyses for infants in the two feeding groups. RESULTS: Of 372 included infants, those achieving full oral feedings had lower incidence of any adverse neurodevelopmental outcome (p < 0.001) compared with those who did not achieve full oral feedings. In multivariable analyses, achievement of full oral feedings by 40 weeks PMA was associated with decreased odds of cognitive, language, and motor delays, cerebral palsy, and any adverse neurodevelopmental outcome at follow-up. CONCLUSION: Achievement of full oral feedings by 40 weeks PMA was associated with better adjusted neurodevelopmental outcomes at 18 to 26 months CA. Inability to fully feed orally at 40 weeks PMA may be a simple, clinically useful marker for risk of adverse neurodevelopmental outcomes.

Regional tissue oxygenation monitoring in the neonatal intensive care unit: evidence for clinical strategies and future directions.

Near-infrared spectroscopy (NIRS)-based monitoring of regional tissue oxygenation (rSO2) is becoming more commonplace in the neonatal intensive care unit (NICU). While increasing evidence supports rSO2 monitoring, actual standards for applying this noninvasive bedside technique continue to evolve. This review highlights the current strengths and pitfalls surrounding practical NIRS-based monitoring in the neonatal population. The physiologic background of rSO2 monitoring is discussed, with attention to understanding oxygen delivery/consumption mismatch and its effects on tissue oxygen extraction. The bedside utility of both cerebral and peripheral rSO2 monitoring in the NICU is then explored from two perspectives: (1) disease/event-specific "responsive" monitoring and (2) "routine," continuous monitoring. Recent evidence incorporating both monitoring approaches is summarized with emphasis on practical applicability in the NICU. Finally, a future paradigm for a broad-based NIRS monitoring strategy is presented, with attention towards improving personalization of neonatal care and ultimately enhancing long-term outcomes.

A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4.

The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients. Importantly, the model recapitulates CCL21 gradients observed experimentally in B cell follicles and interfollicular regions, building confidence in its ability to accurately predict intranodal chemokine distribution. Parameter variation analysis indicates that the directionality of these gradients is robust, but their magnitude is sensitive to these key parameters: chemokine production, diffusivity, matrix binding site availability, and CCR7 abundance. The model indicates that lymph flow shapes intranodal CCL21 gradients, and that CCL19 is functionally important at the boundary between B cell follicles and the T cell area. It also predicts that ACKR4 in LNs prevents CCL19/CCL21 accumulation in efferent lymph, but does not control intranodal gradients. Instead, it attributes the disrupted interfollicular CCL21 gradients observed in Ackr4-deficient LNs to ACKR4 loss upstream. Our novel approach has therefore generated new testable hypotheses and alternative interpretations of experimental data. Moreover, it acts as a framework to investigate gradients at other locations, including those that cannot be visualized experimentally or involve other chemokines.

Dose-response Relationship Between Donor Human Milk, Mother's Own Milk, Preterm Formula, and Neonatal Growth Outcomes.

BACKGROUND: A dose-response relationship between proportions of donor human milk (DHM) intake and in-neonatal intensive care unit (in-NICU) growth rates, if any, remains poorly defined. Objective was to evaluate interrelationships between percentages of DHM, mother's own milk (MOM), and preterm formula (PF) intake and neonatal growth parameters at 36 weeks postmenstrual age or NICU discharge. METHODS: Infants eligible for this single-center retrospective study were inborn at ≤32 weeks gestation or ≤1800 g, stayed in the NICU for ≥7 days, and received enteral nutrition consisting of human milk fortified with Enfamil human milk fortifier acidified liquid. Study exposures were defined as 10% increments in the total volumetric proportions of infant diet provided as MOM, DHM, or PF. Outcomes were growth parameters at 36 weeks postmenstrual age or NICU discharge. Multivariable linear regression modeled the adjusted additive effect of infant diet on individual growth parameters. RESULTS: A total of 314 infants records were eligible for analysis. Using MOM as reference, the adjusted mean growth velocity for weight significantly decreased by 0.17 g ·â€Škg ·â€Šday for every 10% increase in DHM intake, but did not vary with PF intake. The adjusted mean change in weight z score significantly decreased with increasing proportion of DHM intake but significantly improved with increasing PF intake. The adjusted mean head circumference velocity was significantly decreased by 0.01 cm/wk for every 10% increase in DHM intake, in reference to MOM, but did not vary with PF intake. Neither proportion of DHM nor PF intake was associated with length velocity. CONCLUSIONS: When DHM and MOM are fortified interchangeably, preterm infants receiving incremental amounts of DHM are at increased risk of postnatal growth restriction. The dose-response relationship between DHM, MOM, and PF and long-term growth and neurodevelopmental outcomes warrants further research.

Evaluation of the Clinical Utility of Transesophageal Echocardiography and Invasive Monitoring to Assess Right Ventricular Function During and After Pulmonary Endarterectomy.

OBJECTIVE: Patients undergoing pulmonary endarterectomy (PEA) have impaired right ventricular function. The authors sought to assess the clinical utility of commonly used perioperative echocardiographic and right heart catheter measurements in patients undergoing PEA. DESIGN: A single-center prospective observational study. SETTING: The study was conducted in a quaternary care cardiac surgical center in the United Kingdom. PARTICIPANTS: Patients undergoing PEA between April 2015 and January 2016. INTERVENTIONS: Thermodilution cardiac index and echocardiography variables were measured at 3 time points: before sternotomy (T1), after pericardial incision (T2), and after sternal closure (T3). Six-month follow-up echocardiography and 6-minute walk (6-MWT) test were performed. MEASUREMENTS AND MAIN RESULTS: Fifty patients were recruited and complete data sets were available for 41 patients. Tricuspid annular plane systolic excursion declined after pericardial incision and cardiopulmonary bypass (T1: 15 ± 4 mm, T2: 13 ± 4 mm, T3: 7 ± 2 mm; p < 0.0001), returning to baseline 6 months postoperatively. Cardiac index (T1: 2.5 ± 0.7 L/min/m2, T2: 2.6 ± 0.6 L/min/m2, T3: 2.3 ± 0.5 L/min/m2; p = 0.07) and right ventricular fractional area change (T1: 36 ± 11%, T2: 40 ± 12%, T3: 40 ± 9%; p = 0.12) were preserved perioperatively. 6-MWT improved from baseline (294 ± 111 m) to follow-up (357 ± 107 m) (p < 0.001). Pulmonary vascular resistance at T3 correlated moderately with follow-up 6-MWT (R = -0.60). CONCLUSIONS: In patients undergoing PEA, invasive measurements and echocardiography assessment of right ventricular function are not interchangeable. Tricuspid annular plane systolic excursion is not a reliable measure of right ventricular function perioperatively. Pulmonary vascular resistance shows moderate correlation with postoperative functional capacity.

Mesenteric Oxygenation Changes Associated With Necrotizing Enterocolitis and Pneumoperitoneum After Multiple Blood Transfusions: A Case Report.

BACKGROUND: The multifactorial pathology and broad clinical presentation of necrotizing enterocolitis (NEC) development in premature infants make prediction of disease onset extremely challenging. Over the past decade, packed red blood cell (PRBC) transfusions have been temporally linked to the development of NEC in severely anemic preterm infants, although this issue is highly controversial. PURPOSE: In this case study, we describe events of an extremely low birth-weight infant who developed NEC complicated by pneumoperitoneum after receiving multiple PRBC transfusions. Specifically, we describe mesenteric tissue oxygenation trend changes as measured by continuous near-infrared spectroscopy (NIRS) technology. METHODS: As part of a larger prospective, observational investigation, this infant was monitored with NIRS (INVOS 5100C; Medtronic, Boulder, Colorado) before, during, and 48 hours following PRBC transfusions. RESULTS: The infant demonstrated severe, prolonged, and persistent reductions in mesenteric tissue oxygenation following blood transfusions, yet routine physiologic monitoring did not indicate intestinal hypoperfusion or impending NEC onset. IMPLICATIONS FOR PRACTICE: This report demonstrates the ability of NIRS to capture possible tissue ischemia during early stages of NEC that may help guide bedside therapeutic interventions. IMPLICATIONS FOR RESEARCH: Larger cohort studies to evaluate the ability of NIRS to capture early tissue ischemia are essential to validate the feasibility of adding this technology as a routine clinical bedside tool.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Calcium and electrical dynamics in lymphatic endothelium.

KEY POINTS: Endothelial cell function in resistance arteries integrates Ca2+ signalling with hyperpolarization to promote relaxation of smooth muscle cells and increase tissue blood flow. Whether complementary signalling occurs in lymphatic endothelium is unknown. Intracellular calcium and membrane potential were evaluated in endothelial cell tubes freshly isolated from mouse collecting lymphatic vessels of the popliteal fossa. Resting membrane potential measured using intracellular microelectrodes averaged ∼-70 mV. Stimulation of lymphatic endothelium by acetylcholine or a TRPV4 channel agonist increased intracellular Ca2+ with robust depolarization. Findings from Trpv4-/- mice and with computational modelling suggest that the initial mobilization of intracellular Ca2+ leads to influx of Ca2+ and Na+ through TRPV4 channels to evoke depolarization. Lymphatic endothelial cells lack the Ca2+ -activated K+ channels present in arterial endothelium to generate endothelium-derived hyperpolarization. Absence of this signalling pathway with effective depolarization may promote rapid conduction of contraction along lymphatic muscle during lymph propulsion. ABSTRACT: Subsequent to a rise in intracellular Ca2+ ([Ca2+ ]i ), hyperpolarization of the endothelium coordinates vascular smooth muscle relaxation along resistance arteries during blood flow control. In the lymphatic vasculature, collecting vessels generate rapid contractions coordinated along lymphangions to propel lymph, but the underlying signalling pathways are unknown. We tested the hypothesis that lymphatic endothelial cells (LECs) exhibit Ca2+ and electrical signalling properties that facilitate lymph propulsion. To study electrical and intracellular Ca2+ signalling dynamics in lymphatic endothelium, we excised collecting lymphatic vessels from the popliteal fossa of mice and removed their muscle cells to isolate intact LEC tubes (LECTs). Intracellular recording revealed a resting membrane potential of ∼-70 mV. Acetylcholine (ACh) increased [Ca2+ ]i with a time course similar to that observed in endothelium of resistance arteries (i.e. rapid initial peak with a sustained 'plateau'). In striking contrast to the endothelium-derived hyperpolarization (EDH) characteristic of arteries, LECs depolarized (>15 mV) to either ACh or TRPV4 channel activation. This depolarization was facilitated by the absence of Ca2+ -activated K+ (KCa ) channels as confirmed with PCR, persisted in the absence of extracellular Ca2+ , was abolished by LaCl3 and was attenuated ∼70% in LECTs from Trpv4-/- mice. Computational modelling of ion fluxes in LECs indicated that omitting K+ channels supports our experimental results. These findings reveal novel signalling events in LECs, which are devoid of the KCa activity abundant in arterial endothelium. Absence of EDH with effective depolarization of LECs may promote the rapid conduction of contraction waves along lymphatic muscle during lymph propulsion.

Consequences of intravascular lymphatic valve properties: a study of contraction timing in a multi-lymphangion model.

The observed properties of valves in collecting lymphatic vessels include transmural pressure-dependent bias to the open state and hysteresis. The bias may reduce resistance to flow when the vessel is functioning as a conduit. However, lymphatic pumping implies a streamwise increase in mean pressure across each valve, suggesting that the bias is then potentially unhelpful. Lymph pumping by a model of several collecting lymphatic vessel segments (lymphangions) in series, which incorporated these properties, was investigated under conditions of adverse pressure difference while varying the refractory period between active muscular contractions and the inter-lymphangion contraction delay. It was found that many combinations of the timing parameters and the adverse pressure difference led to one or more intermediate valves remaining open instead of switching between open and closed states during repetitive contraction cycles. Cyclic valve switching was reliably indicated if the mean pressure in a lymphangion over a cycle was higher than that in the lymphangion upstream, but either lack of or very brief valve closure could cause mean pressure to be lower downstream. Widely separated combinations of refractory period and delay time were found to produce the greatest flow-rate for a given pressure difference. The efficiency of pumping was always maximized by a long refractory period and lymphangion contraction starting when the contraction of the lymphangion immediately upstream was peaking. By means of an ex vivo experiment, it was verified that intermediate valves in a chain of pumping lymphangions can remain open, while the lymphangions on either side of the open valve continue to execute contractions.

Transport across Schlemm's canal endothelium and the blood-aqueous barrier.

The majority of trabecular outflow likely crosses Schlemm's canal (SC) endothelium through micron-sized pores, and SC endothelium provides the only continuous cell layer between the anterior chamber and episcleral venous blood. SC endothelium must therefore be sufficiently porous to facilitate outflow, while also being sufficiently restrictive to preserve the blood-aqueous barrier and prevent blood and serum proteins from entering the eye. To understand how SC endothelium satisfies these apparently incompatible functions, we examined how the diameter and density of SC pores affects retrograde diffusion of serum proteins across SC endothelium, i.e. from SC lumen into the juxtacanalicular tissue (JCT). Opposing retrograde diffusion is anterograde bulk flow velocity of aqueous humor passing through pores, estimated to be approximately 5 mm/s. As a result of this relatively large through-pore velocity, a mass transport model predicts that upstream (JCT) concentrations of larger solutes such as albumin are less than 1% of the concentration in SC lumen. However, smaller solutes such as glucose are predicted to have nearly the same concentration in the JCT and SC. In the hypothetical case that, rather than micron-sized pores, SC formed 65 nm fenestrae, as commonly observed in other filtration-active endothelia, the predicted concentration of albumin in the JCT would increase to approximately 50% of that in SC. These results suggest that the size and density of SC pores may have developed to allow SC endothelium to maintain the blood-aqueous barrier while simultaneously facilitating aqueous humor outflow.

Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress.

OBJECTIVE: To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ. METHODS: Twelve rats were infused with saline (intravenous infusion, 0.2 mL/min/100 g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as lymphocyte velocity and density before, during, and after infusion. RESULTS: A 10-fold increase in lymphocyte velocity (0.1-1 mm/s) and a sixfold increase in flow rate (0.1-0.6 µL/min), were observed post infusion, respectively. There were also increases in contraction frequency and fractional pump flow one minute post infusion. Time-averaged wall shear stress increased 10 fold post infusion to nearly 1.5 dynes/cm(2) . Similarly, maximum shear stress rose from 5 to 40 dynes/cm(2) . CONCLUSIONS: Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymphocyte velocity, and shear stress were significant. Lymph pumping increased post infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymphocyte velocity, and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function.

Feeding preterm infants during red blood cell transfusion is associated with a decline in postprandial mesenteric oxygenation.

OBJECTIVE: To evaluate the mesenteric tissue oxygenation response in preterm infants fed and not fed during red blood cell (RBC) transfusions. STUDY DESIGN: Prospective, observational comparison of mesenteric oxygenation using near-infrared spectroscopy in preterm infants (<33 weeks' at birth) who were fed or not fed during RBC transfusion. Tissue oxygenation means were examined up to 48 hours after each transfusion event. RESULTS: Mean mesenteric regional oxygen saturation (rSO2) slopes during RBC transfusion of fed (n = 9) vs not fed (n = 8) infants ranged from -0.23 to +0.23 (mean 0.04) with no differences between groups (P = .480). However, following transfusions, postprandial mesenteric oxygenation means significantly declined in infants fed during transfusion compared with infants not fed during transfusion (P < .001). Infants fed during RBC transfusion had a mean 2.16 point decrease in rSO2 mesenteric oxygenation with each sequential feeding post-transfusion, whereas infants not fed during RBC transfusion increased their rSO2 postprandial mesenteric oxygenation by a mean of 2.09 points. CONCLUSIONS: Mesenteric tissue oxygenation during RBC transfusion is not influenced by feeding status. However, infants fed during RBC transfusion had, for the next 15 hours, decreasing postprandial mesenteric tissue oxygenation patterns compared with infants not fed during RBC transfusion. Feeding during RBC transfusions may increase the risk for mesenteric ischemia and the development of transfusion-related necrotizing enterocolitis in preterm infants.

Primary and secondary lymphatic valve development: molecular, functional and mechanical insights.

Fluid homeostasis in vertebrates critically relies on the lymphatic system forming a hierarchical network of lymphatic capillaries and collecting lymphatics, for the efficient drainage and transport of extravasated fluid back to the cardiovascular system. Blind-ended lymphatic capillaries employ specialized junctions and anchoring filaments to encourage a unidirectional flow of the interstitial fluid into the initial lymphatic vessels, whereas collecting lymphatics are responsible for the active propulsion of the lymph to the venous circulation via the combined action of lymphatic muscle cells and intraluminal valves. Here we describe recent findings on molecular and physical factors regulating the development and maturation of these two types of valves and examine their role in tissue-fluid homeostasis.

The effect of static and dynamic loading on degradation of PLLA stent fibers.

Understanding how polymers such as PLLA degrade in vivo will enhance biodegradable stent design. This study examined the effect of static and dynamic loads on PLLA stent fibers in vitro. The stent fibers (generously provided by TissueGen, Inc.) were loaded axially with 0 N, 0.5 N, 1 N, or 0.125-0.25 N (dynamic group, 1 Hz) and degraded in PBS at 45 °C for an equivalent degradation time of 15 months. Degradation was quantified through changes in tensile mechanical properties. The mechanical behavior was characterized using the Knowles strain energy function and a degradation model. A nonsignificant increase in fiber stiffness was observed between 0 and 6 months followed by fiber softening thereafter. A marker of fiber softening, ß, increased between 9 and 15 months in all groups. At 15 months, the ß values in the dynamic group were significantly higher compared to the other groups. In addition, the model indicated that the degradation rate constant was smaller in the 1-N (0.257) and dynamic (0.283) groups compared to the 0.5-N (0.516) and 0-N (0.406) groups. While the shear modulus fluctuated throughout degradation, no significant differences were observed. Our results indicate that an increase in static load increased the degradation of mechanical properties and that the application of dynamic load further accelerated this degradation.

Peripheral intravenous and central catheter algorithm: a proactive quality initiative.

Peripheral intravenous (PIV) infiltrations causing tissue damage is a global issue surrounded by situations that make vascular access decisions difficult. The purpose of this quality improvement project was to develop an algorithm and assess its effectiveness in reducing PIV infiltrations in neonates. The targeted subjects were all infants in our neonatal intensive care unit (NICU) with a PIV catheter. We completed a retrospective chart review of the electronic medical record to collect 4th quarter 2012 baseline data. Following adoption of the algorithm, we also performed a daily manual count of all PIV catheters in the 1st and 2nd quarters 2013. Daily PIV days were defined as follows: 1 patient with a PIV catheter equals 1 PIV day. An infant with 2 PIV catheters in place was counted as 2 PIV days. Our rate of infiltration or tissue damage was determined by counting the number of events and dividing by the number of PIV days. The rate of infiltration or tissue damage was reported as the number of events per 100 PIV days. The number of infiltrations and PIV catheters was collected from the electronic medical record and also verified manually by daily assessment after adoption of the algorithm. To reduce the rate of PIV infiltrations leading to grade 4 infiltration and tissue damage by at least 30% in the NICU population. Incidence of PIV infiltrations/100 catheter days. The baseline rate for total infiltrations increased slightly from 5.4 to 5.68/100 PIV days (P = .397) for the NICU. We attributed this increase to heightened awareness and better reporting. Grade 4 infiltrations decreased from 2.8 to 0.83/100 PIV catheter days (P = .00021) after the algorithm was implemented. Tissue damage also decreased from 0.68 to 0.3/100 PIV days (P = .11). Statistical analysis used the Fisher exact test and reported as statistically significant at P < .05. Our findings suggest that utilization of our standardized decision pathway was instrumental in providing guidance for problem solving related to vascular access decisions. We feel this contributed to the overall reduction in grade 4 intravenous infiltration and tissue damage rates. Grade 4 infiltration reductions were highly statistically significant (P = .00021).

Assessing ethical behavior and self-control in elite ultimate championships: a cross-sectional study using the spirit of the game scoring system.

Introduction: Implementing a self-refereeing system presents a unique challenge in sports education, particularly in academic and training settings where officiated sports prevail. However, Ultimate Frisbee stands out by entrusting players with both athlete and referee roles, introducing distinctive ethical complexities. This manuscript is intended to evaluate ethical behavior and self-control within the Spirit of the Game (SOTG) scoring system in Elite Ultimate. To address these, Ultimate employs the (SOTG) scoring system, integral since the sport's inception in the late 1980s. SOTG aims to enhance and evaluate athletes' ethical conduct. This study evaluates SOTG's effectiveness in elite-level Ultimate, analyzing variations across divisions and age groups in three high-level tournaments. Methods: Using a cross-sectional design, data were collected from five international Ultimate tournaments in 2022. Teams spanned diverse age groups (under 17 to over 50) and divisions (women's, mixed, open). Post-match, teams assessed opponents' SOTG in five domains: Rules knowledge, fouls, fairness, attitude/self-control, and communication. Ratings used a 5-point Likert scale ("poor" to "excellent"). An overall SOTG score was calculated by aggregating domain scores. Results: Our study consistently revealed high SOTG scores, reflecting strong sportsmanship. "Positive attitude and self-control" consistently ranked highest, while "Knowledge and use of the rules" scored lowest. Divisional differences in SOTG were statistically insignificant. Notably, WMUCC2022 (participants aged 30+) had significantly higher SOTG scores, possibly indicating age-related self-control improvement or evolving sport culture. Lower rules knowledge scores may stem from linguistic translation challenges. Conclusion: Self-refereeing promotes ethical behavior across divisions and age groups. SOTG underscores sportsmanship's importance and aligns with International Olympic Committee (IOC) and with Sustainable Development Goals (SDGs), particularly SDG 3, 4, 5 and 16 fostering a fairer, healthier, and more peaceful world.

Parameter sensitivity analysis of a lumped-parameter model of a chain of lymphangions in series.

Any disruption of the lymphatic system due to trauma or injury can lead to edema. There is no effective cure for lymphedema, partly because predictive knowledge of lymphatic system reactions to interventions is lacking. A well-developed model of the system could greatly improve our understanding of its function. Lymphangions, defined as the vessel segment between two valves, are the individual pumping units. Based on our previous lumped-parameter model of a chain of lymphangions, this study aimed to identify the parameters that affect the system output the most using a sensitivity analysis. The system was highly sensitive to minimum valve resistance, such that variations in this parameter caused an order-of-magnitude change in time-average flow rate for certain values of imposed pressure difference. Average flow rate doubled when contraction frequency was increased within its physiological range. Optimum lymphangion length was found to be some 13-14.5 diameters. A peak of time-average flow rate occurred when transmural pressure was such that the pressure-diameter loop for active contractions was centered near maximum passive vessel compliance. Increasing the number of lymphangions in the chain improved the pumping in the presence of larger adverse pressure differences. For a given pressure difference, the optimal number of lymphangions increased with the total vessel length. These results indicate that further experiments to estimate valve resistance more accurately are necessary. The existence of an optimal value of transmural pressure may provide additional guidelines for increasing pumping in areas affected by edema.