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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.

The lymphatic system maintains bodily fluid balance by returning interstitial fluid to the venous system. Flow can occur through a combination of extrinsic pumping, due to forces from surrounding tissues, and intrinsic pumping involving contractions of muscle in the lymphatic vessel walls. Lymph transport is important not only for fluid homeostasis, but also for immune function, as lymph is a carrier for immune cells. Lymphatic muscle cells exhibit cardiac-like phasic contractions to generate flow and smooth-muscle-like tonic contractions to regulate flow. Lymphatic vessels therefore act as both active pumps and conduits. Lymphatic vessels are sensitive to mechanical stimuli, including flow-induced shear stresses and pressure-induced vessel stretch. These forces modulate biochemical pathways, leading to changes in intracellular calcium and interaction with regulatory and contractile proteins. In a multiscale computational model of phasic and tonic contractions in lymphatic muscle coupled to a lumped-parameter model of lymphatic pumping, we tested different models of the mechanical feedback mechanisms exhibited by lymphatics in experiments. Models were validated using flow and pressure experiments not used in the models’ construction. The final model shows that with flow-induced shear stress modulation, there is a small change in flow rate but an increase in muscle efficiency. A better understanding of the mechanobiology of lymphatic contractions can help guide future lymphatic vessel experiments, providing a basis for developing better treatments for lymphatic dysfunction.

The lymphatics maintain fluid balance by returning interstitial fluid to veins via contraction/compression of vessel segments with check valves. Disruption of lymphatic pumping can result in a condition called lymphedema with interstitial fluid accumulation. Lymphedema treatments are often ineffective, which is partially attributable to insufficient understanding of specialized lymphatic muscle lining the vessels. This muscle exhibits cardiac-like phasic contractions and smooth muscle-like tonic contractions to generate and regulate flow. To understand the relationship between this sub-cellular contractile machinery and organ-level pumping, we have developed a multiscale computational model of phasic and tonic contractions in lymphatic muscle and coupled it to a lymphangion pumping model. Our model uses the sliding filament model (Huxley in Prog Biophys Biophys Chem 7:255–318, 1957) and its adaptation for smooth muscle (Mijailovich in Biophys J 79(5):2667–2681, 2000). Multiple structural arrangements of contractile components and viscoelastic elements were trialed but only one provided physiologic results. We then coupled this model with our previous lumped parameter model of the lymphangion to relate results to experiments. We show that the model produces similar pressure, diameter, and flow tracings to experiments on rat mesenteric lymphatics. This model provides the first estimates of lymphatic muscle contraction energetics and the ability to assess the potential effects of sub-cellular level phenomena such as calcium oscillations on lymphangion outflow. The maximum efficiency value predicted (40%) is at the upper end of estimates for other muscle types. Spontaneous calcium oscillations during diastole were found to increase outflow up to approximately 50% in the range of frequencies and amplitudes tested. Supplementary Information The online version contains supplementary material available at 10.1007/s10237-021-01501-0.

Background Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them. Methods A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions. Results Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45–0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45–0.96; local skin infections: OR = 0.41, 95% CI = 0.26–0.65; chemical burns: OR = 0.46, 95% CI = 0.26–0.83; thermal burns: OR = 0.51, 95% CI = 0.27–0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33–0.67; pressure: aOR = 0.51, 95% CI = 0.34–0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51–0.99; perineal: aOR = 0.52, 95% CI = 0.36–0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed. Conclusions Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

To describe characteristics and outcomes of Māori and European patients admitted to New Zealand intensive care units (ICUs) between 2009 and 2018.A retrospectively designed prospective cohort study. New Zealand Ministry of Health National Minimum Dataset matched to the Australia New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. The primary outcome was day-180 mortality. Secondary outcomes were ICU mortality, hospital mortality, discharge to home, ICU length of stay, hospital length of stay and survival time. We report associations between Māori ethnicity and each outcome, with European as the reference category, using regression analyses to adjust sequentially for site, deprivation status, sex, year of admission, the Charlson comorbidity index, age, admission source and type, ICU admission diagnosis, ventilation status and illness severity based on physiological parameters.Māori admitted to ICU were on average 13 years younger than European patients. A total of 968 of 9,681 (10%) Māori and 2,732 of 42,871 (5.2%) European patients were admitted after trauma, and 740 of 9,681 (7.6%) and 2,318 of 42,871 (4.4%) were admitted with sepsis respectively. A total of 1,550 of 9,681 (16.0%) Māori and 6,407 of 42,871 (14.9%) European patients died within 180 days of ICU admission; odds ratio (OR) 1.08; 95% CI, 1.02 to 1.15. When adjusted for age, the OR for day-180 mortality for Māori versus European patients increased substantially. The OR decreased after adjustment for admission source and type, and after accounting for Māori having a higher comorbidity index and more severe illness than European patients. In the final model, incorporating adjustment for all specified variables, Māori ethnicity was not associated with day-180 mortality (adjusted OR 1.01; 95%CI, 0.92 to 1.10). Findings were similar for all secondary outcomes.Compared to European patients, Māori were markedly more likely to be admitted to the ICU after trauma or with sepsis. Despite Māori being on average 13 years younger at ICU admission than their European counterparts, they had more co-morbidities, higher illness severity and a higher risk of dying within 180 days.

Pre-pregnancy or first trimester biomarkers predicting preterm delivery are lacking. The purpose of this study was to determine whether maternal H-antigen (secretor status) is a potential biomarker for preterm delivery. This cohort study examined maternal saliva samples and birth data gathered by the National Children’s Study Vanguard pilot phase (2009–2014) and included 300 women who were ≥18 years old and provided birth data and saliva samples. The maternal secretor status phenotype was determined by quantifying H-antigen in saliva using enzyme-linked immunoassay. Mothers were stratified by secretor status and multivariable analysis estimated adjusted associations with preterm delivery. Maternal lack of H-antigen production was an independent risk factor for preterm delivery after adjusting for known confounders (aOR 4.53; 95% CI: 1.74, 11.81; P = 0.002). Maternal H-antigen may be a biomarker identifying women at-risk for preterm delivery. Prospective cohort studies validating these findings are needed.

Background: Effects of breast milk (BM) enhancement on long-term BM feeding in preterm infants discharged from the neonatal intensive care unit (NICU) have not been examined previously. This study ...

Purpose of Review This article provides an overview of the common and important chest injuries that the anesthesiologist may encounter in patients following trauma including blunt injury, pneumothorax, hemothorax, blunt aortic injury, and blunt cardiac injury. Recent Findings Rib fractures are frequently associated with chest injury and are associated with significant pain and other complications. Regional anesthesia techniques combined with a multimodal analgesic strategy can improve patient outcomes and reduce complications. There is increasing evidence for paravertebral blocks for this indication, and the myofascial plane blocks are a popular emerging technique. Recent changes to recommended management of tension pneumothorax are also described. Summary Chest trauma is commonly encountered, and anesthesiologists have the potential to significantly improve morbidity and mortality in this group of patients.

Swelling of lymph nodes is commonly observed during the adaptive immune response, yet the impact on T cell trafficking and subsequent immune response is not well known. To better understand the effect of macro-scale alterations, we developed an agent-based model of the lymph node para-cortex, describing T cell trafficking and response to antigen-presenting dendritic cells alongside swelling-induced changes in T cell recruitment and egress, and regulation of expression of egress-modulating T cell receptor Sphingosine-1-phosphate receptor-1. Analysis of effector T cell response under varying swelling conditions showed that swelling consistently aided T cell activation. However, subsequent effector CD8+ T cell production could be reduced if swelling occurred too early in the T cell proliferative phase or if T cell cognate frequency was low due to increased opportunity for T cell exit. Temporarily extending retention of newly differentiated effector T cells, mediated by Sphingosine-1-phosphate receptor-1 expression, mitigated any negative effects of swelling by allowing facilitation of activation to outweigh increased access to exit areas. These results suggest targeting temporary effector T cell retention and egress associated with swelling may offer new ways to modulate effector TC responses in, for example, immuno-suppressed patients and optimisation of vaccine design.

There has existed a severe ventilator deficit in much of the world for many years, due in part to the high cost and complexity of traditional ICU ventilators. This was highlighted and exacerbated by the emergence of the COVID-19 pandemic, during which the increase in ventilator production rapidly overran the global supply chains for components. In response, we propose a new approach to ventilator design that meets the performance requirements for COVID-19 patients, while using components that minimise interference with the existing ventilator supply chains. The majority of current ventilator designs use proportional valves and flow sensors, which remain in short supply over a year into the pandemic. In the proposed design, the core components are on-off valves. Unlike proportional valves, on-off valves are widely available, but accurate control of ventilation using on-off valves is not straightforward. Our proposed solution combines four on-off valves, a two-litre reservoir, an oxygen sensor and two pressure sensors. Benchtop testing of a prototype was performed with a commercially available flow analyser and test lungs. We investigated the accuracy and precision of the prototype using both compressed gas supplies and a portable oxygen concentrator, and demonstrated the long-term durability over 15 days. The precision and accuracy of ventilation parameters were within the ranges specified in international guidelines in all tests. A numerical model of the system was developed and validated against experimental data. The model was used to determine usable ranges of valve flow coefficients to increase supply chain flexibility. This new design provides the performance necessary for the majority of patients that require ventilation. Applications include COVID-19 as well as pneumonia, influenza, and tuberculosis, which remain major causes of mortality in low and middle income countries. The robustness, energy efficiency, ease of maintenance, price and availability of on-off valves are all advantageous over proportional valves. As a result, the proposed ventilator design will cost significantly less to manufacture and maintain than current market designs and has the potential to increase global ventilator availability.

Contemporary packed red blood cell transfusion practices in anaemic preterm infants are primarily based on measurement of hemoglobin or haematocrit. In neonatal intensive care units, most preterm infants receive at least 1 packed red cell transfusion as standard treatment for anaemia of prematurity. Clinicians are faced with a common question "at what threshold should anaemic preterm infants receive packed red blood cell transfusion?". While evidence from interventional trials offers a range of haemoglobin levels to clinicians on thresholds to initiate red cell transfusion, it does not offer identification of exact haemoglobin level at which regional oxygenation and perfusion gets compromised. Assessment of regional oxygenation using near infrared spectroscopy and perfusion using ultrasound could offer a personalized transfusion medicine approach to optimize transfusion practices. We conducted a systematic review of the literature to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion in anaemic preterm infants. MEDLINE, Embase, Maternity and Infant Care database were searched up to March 2021. Publications identified were screened and relevant data was extracted. Changes to regional oxygenation and/or perfusion monitoring before and after packed red blood cell transfusion were the primary outcomes. 44 out of 755 studies met the inclusion criteria and were included in the final analysis. Most were prospective, observational studies in stable preterm infants. Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when hemoglobin

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.

BACKGROUND: Children born prematurely (

Background Abnormal blood flow patterns can alter the material properties of the thoracic aorta via altered vascular biology and tissue biomechanics. In-vivo haemodynamic assessment of the aorta is yet to penetrate clinical practice due to our limited understanding of its effect on aortic wall properties. The decision for surgical treatment is based on size thresholds, limited to a single measurement of aortic diameter from routine imaging, although many aortic dissections (40–60%) occur below these size thresholds. This multi-centre study aims to assess the clinical utility of biomechanics principles in thoracic aortic aneurysm (TAA) risk rupture prediction using a substantial sample size. Methods Fifty-five patients undergoing surgery for root or ascending TAA were recruited from five cardiac centres. Bicuspid aortic valves and connective tissue disease were excluded from this study.Haemodynamic assessment Pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI) were conducted. Direct 4D-flow analysis and computational fluid dynamics (CFD) were performed creating detailed wall shear stress (WSS) maps across the whole aneurysms. Aortic wall assessment The aneurysmal aortic sample was obtained from surgery and subjected to region specific uniaxial failure tests in the circumferential and longitudinal directions, as well as delamination testing within the aortic media. Whole aneurysm histological characterisation was also conducted using computational pathology techniques. Blood flow, tissue mechanics and microstructural properties were used to develop a risk prediction model with assessment of elastin, collagen and smooth muscle cell composition, as well as failure strain assessment and dissection energy function. Results Outcomes of mechanical properties were: Young's Elastic Modulus as a measure of aortic stiffness (0.85 MPa ±0.69), as well as maximal tensile strength (0.49 MPa ± 0.36), which demonstrated reduced aortic wall strength in the outer curvature. This correlated with increased wall shear stress (WSS) (up to 10 Pa) and flow velocity (up to 43 l/min). Regions of abnormal flow and tissue mechanics correlated significantly with degraded medial microstructure (elastin abundance: 34 vs 66%; collagen abundance 26 vs 57%, p Conclusions CFD modelling has the potential to provide a risk prediction of acute events in TAA beyond the current size classification, as validated by altered aortic tissue properties. Future longitudinal studies are warranted to validate this methods in moderately enlarging thoracic aortas. Flow, mechanical, histology properties Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): NIHR Imperial College BRC

Nutrient requirements of preterm neonates may be substantial, to support growth and maturation processes in the presence of challenging post-natal circumstances. This may be accompanied by substantial intestinal oxygen requirements. Preterm neonates may not be able to meet these oxygen requirements, due to a developmental delay in intestinal oxygenation regulation mechanisms. This review summarizes the available literature on post-natal maturation of intestinal oxygenation mechanisms and translates these changes into clinical observations and potential implications for preterm neonates. The different mechanisms that may be involved in regulation of intestinal oxygenation, regardless of post-natal age, are first discussed. The contribution of these mechanisms to intestinal oxygenation regulation is then evaluated in newborn and mature intestine. Finally, the course of clinical observations is used to translate these findings to potential implications for preterm neonates.

In this paper, we present findings on micro-concentrator photovoltaic cells composed of lattice matched subcells grown on GaAs and InP substrates, which are stacked into single, four-terminal devices using micro-transfer printing. The design, modeling, growth, fabrication and assembly of the devices will be described, and potential interconnection schemes to achieve efficient, two-terminal strings of cells with flexible current and voltage outputs and resilience to defects is discussed.

Lymphogenic spread is associated with poor prognosis in epithelial ovarian cancer (EOC), yet little is known regarding roles of non-peri-tumoural lymphatic vessels (LVs) outside the tumour microenvironment that may impact relapse. The aim of this feasibility study was to assess whether inflammatory status of the LVs and/or changes in the miRNA profile of the LVs have potential prognostic and predictive value for overall outcome and risk of relapse. Samples of macroscopically normal human lymph LVs (n=10) were isolated from the external iliac vessels draining the pelvic region of patients undergoing debulking surgery. This was followed by quantification of the inflammatory state (low, medium and high) and presence of cancer-infiltration of each LV using immunohistochemistry. LV miRNA expression profiling was also performed, and analysed in the context of high versus low inflammation, and cancer-infiltrated versus non-cancer-infiltrated. Results were correlated with clinical outcome data including relapse with an average follow-up time of 13.3 months. The presence of a high degree of inflammation correlated significantly with patient relapse (p=0.033). Cancer-infiltrated LVs showed a moderate but non-significant association with relapse (p=0.07). Differential miRNA profiles were identified in cancer-infiltrated LVs and those with high versus low inflammation. In particular, several members of the let-7 family were consistently down-regulated in highly inflamed LVs (>1.8-fold, p

In the last year, various leaders at the Federal Trade Commission and the Antitrust Division of the Department of Justice have held out Section 2 of the Sherman Act as a vehicle for targeting acquisitions involving nascent competitors—including consummated mergers—that raise potential antitrust concerns. Three propositions, in particular, have invited controversy: (1) claims under Section 2 challenging the acquisition of a nascent competitor by a monopolist (or would-be monopolist) present a lower bar than Section 7 with respect to proving competitive effects and causation; (2) evidence of intent may be used as a proxy for probable harm; and (3) Section 2 may aid enforcers in challenging serial acquisitions—of targets with low market shares or start-ups outside of the acquirer’s primary market—on a course-of-conduct or “monopoly broth” theory. These three points merit careful discussion. In May 2020, the American Bar Association Section of Antitrust Law (“ABA”) hosted an important panel, entitled A Lesser Hurdle? Exploring Section 2 as Applied to Consummated Mergers, to discuss competing views on this topic. In a similar spirit, this paper summarizes the key arguments on the topic to date, drawing on both the ABA panel discussion and recent scholarship. Rather than attempt to resolve the debate here, we capture the key points on both sides of each controversy to serve as a departure point for future discussion.

We demonstrate a novel concept for III-V engineered substrate cost reduction that does not rely on chemical–mechanical polishing or low-throughput release layer etching. With the potential for significant reduction to III-V substrate cost, the details of this concept are provided, as well as a demonstration of III-V devices grown on a membrane removed from its source substrate and bonded to a non-native target handle. The GaAs solar cell on membrane one-sun and concentration AM1.5 efficiencies register 16.2% and 19.1%, respectively, prior to the application of anti-reflection coating. This is a discrepancy of 2% (one-sun) and 1.2% (concentration) absolute versus a nominally identical control GaAs device, indicating the capability for high performance at reduced cost.

The paper describes the extension of a previously developed model of pressure-dependent contraction rate to the case of multiple lymphangions. Mechanical factors are key modulators of active lymphatic pumping. As part of the evolution of our lumped-parameter model to match experimental findings, we have designed an algorithm whereby the time until the next contraction depends on lymphangion transmural pressure in the contraction just completed. The functional dependence of frequency on pressure is quantitatively matched to isobaric contraction experiments on isolated lymphatic segments. When each of several lymphangions is given this ability, a scheme for their coordination must be instituted to match the observed synchronisation. Accordingly, and in line with an experiment on an isolated lymphatic vessel segment in which we measured contraction sequence and conduction delay, we took the fundamental principle to be that local timing can be overridden by signals to initiate contraction that start in adjacent lymphangions, conducted with a short delay. The scheme leads to retrograde conduction when the lymphangion chain is pumping against an adverse pressure difference, but antegrade conduction when contractions occur with no or a favourable pressure difference. Abolition of these conducted signals leads to chaotic variation of cycle-mean flow-rate from the chain, diastolic duration in each lymphangion, and inter-lymphangion delays. Chaotic rhythm is also seen under other circumstances. Because the model responds to increasing adverse pressure difference by increasing the repetition rate of contractions, it maintains time-average output flow-rate better than one with fixed repetition rate.

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 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.

Leukocyte migration is critically important during all protective and pathological immune and inflammatory responses. Chemokines play fundamental roles in this process, and chemokine concentration gradients stimulate the directional migration of leukocytes. The formation and regulation of these gradients is poorly understood. These are complex processes that depend on the specific properties of each chemokine and interactions between physical, biological and biochemical processes, including production, diffusion, advection, scavenging, post-translational modification, and extracellular matrix (ECM) binding. While some of these mechanisms have been investigated in isolation or limited combinations, more integrative research is required to provide a quantitative knowledge base that explains how chemokine gradients are established and maintained, and how cells respond to, and modify, these gradients.

Additive manufacturing platforms are transforming research and industrial sectors worldwide. In regenerative medicine and pharmaceutical applications, they facilitate the development of patient-specific devices for implantation, as well as in vitro models of tissues and organs for disease modelling and drug screening. A key example is extrusion-based bioprinting, where a bioink that contains cells, biomolecules and a support matrix (often hydrogel), is extruded through a narrow capillary onto a platform forming the desired structure. The printing parameters and hydrogel flow behavior likely determine the extent to which cells are damaged mechanically as they pass through the capillary. Here, we present direct observations of the hydrogels and suspended cells during the printing process to help elucidate conditions potentially leading to mechanical damage and cell death. Light-sheet fluorescence microscopy was applied to observe the real-time flow of bioinks through a capillary mimicking the conditions found in bioprinting. Bioink formulations exhibiting constant and shear thinning viscosities, along with UV-crosslinked gelatin methacrylol (GelMA) were studied, and cell viability of post-printed gels were measured via fluorescent imaging. Cell tracking enabled flow profiles of bioinks to be deduced. In agreement with current flow simulations, the constant and shear thinning formulations displayed a Poiseuille flow profile although with a plug velocity profile for the latter. The UV-crosslinked GelMA formulation exhibited a two-phase annular flow with gel morphologies depicting gross-melt fractures attributed to over-gelled hydrogels. Cell viability was higher in UV-crosslinked GelMA at high flow rates compared to uncrosslinked GelMA. The findings presented here will improve modeling cell-material flow during bioprinting through accurate estimation of flow conditions, in particular for complex materials. The novel imaging approach could be further exploited to provide process monitoring and feedback to improve the outcomes of 3D bioprinting.

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.

Does target cell depletion, innate immunity, or adaptive immunity play the dominant role in controlling primary acute viral infections? Why do some individuals have higher peak virus titers than others? Answering these questions is a basic problem in immunology and can be particularly difficult in humans due to limited data, heterogeneity in responses in different individuals, and limited ability for experimental manipulation. We address these questions for infections following vaccination with the live attenuated Yellow Fever Virus (YFV-17D) by analyzing viral load data from 80 volunteers. Using a mixed effects modeling approach, we find that target cell depletion models do not fit the data as well as innate or adaptive immunity models. Examination of the fits of the innate and adaptive immunity models to the data allows us to select a minimal model that gives improved fits by widely used model selection criteria (AICc and BIC), and explains why it is hard to distinguish between the innate and adaptive immunity models. We then ask why some individuals have over 1000 fold higher virus titers than others, and find that most of the variation arises from differences in the initial/maximum growth rate of the virus in different individuals.

Lymphatic valves facilitate the lymphatic system’s role in maintaining fluid homeostasis. Malformed valves are found in several forms of primary lymphœdema, resulting in incurable swelling of the tissues and immune dysfunction. Their experimental study is complicated by their small size and operation in low pressure and low Reynolds number environments. Mathematical models of these structures can give insight and complement experimentation. In this work, we present the first valve geometry reconstructed from confocal imagery and used in the construction of a subject-specific model in a closing mode. A framework is proposed whereby an image is converted into a valve model. An FEA study was performed to identify the significance of the shear modulus, the consequences of smoothing the leaflet surface and the effect of wall motion on valve behaviour. Smoothing is inherent to any analysis from imagery. The nature of the image, segmentation and meshing all cause attenuation of high-frequency features. Smoothing not only causes loss of surface area but also the loss of high-frequency geometric features which may reduce stiffness. This work aimed to consider these effects and inform studies by taking a manual reconstruction and through manifold harmonic analysis, attenuating higher frequency features to replicate lower resolution images or lower degree-of-freedom reconstructions. In conclusion, two metrics were considered: trans-valvular pressure required to close the valve, Δ P c , and the retrograde volume displacement after closure. The higher Δ P c , the greater the volume of lymph that will pass through the valve during closure. Retrograde volume displacement after closure gives a metric of compliance of the valve and for the quality of the valve seal. In the case of the image-specific reconstructed valve, removing features with a wavelength longer than four μ m caused changes in Δ P c . Varying the shear modulus from 10 kPa to 60 kPa caused a 3.85-fold increase in the retrograde volume displaced. The inclusion of a non-rigid wall caused Δ P c to increase from 1.56 to 2.52 cmH2O.

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.

This study suggests a new framework that empirically quantifies the temporally disaggregate economic impacts. Utilizing only secondary data, including post-event information on concurrent demand and value-added changes in the wake of Hurricanes Katrina and Rita, the framework is used to identify the technological changes in production that actually occurred after a major disruption. Two methodologies are developed for the framework and data analysis: a quasi-experimental model and an economic model. The Holt–Winters time-series approach is used to estimate normal economic trends under the assumption that the two hurricanes had not occurred, and the results are compared to actual trends. The gaps between the estimated and actual trends represent the direct impacts. We utilized the flexible national interstate economic model to construct a month-to-month supply-side version of the national interstate economic model and measure the total economic impacts of Hurricanes Katrina and Rita by month, state and industry, including adaptations. The new framework, which provides estimates of economic impact adaptation process and resilient results, refines the often substantially overstated impacts provided by the application of conventional economic models. The suggested approach can be used to address questions about the effects of time, distance, and industry linkages, and hence the dynamics of conflict activities.

All protective and pathogenic immune and inflammatory responses rely heavily on leukocyte migration and localization. Chemokines are secreted chemoattractants that orchestrate the positioning and migration of leukocytes through concentration gradients. The mechanisms underlying chemokine gradient establishment and control include physical as well as biological phenomena. Mathematical models offer the potential to both understand this complexity and suggest interventions to modulate immune function. Constructing models that have powerful predictive capability relies on experimental data to estimate model parameters accurately, but even with a reductionist approach, most experiments include multiple cell types, competing interdependent processes and considerable uncertainty. Therefore, we propose the use of reduced modelling and experimental frameworks in complement, to minimize the number of parameters to be estimated. We present a Bayesian optimization framework that accounts for advection and diffusion of a chemokine surrogate and the chemokine CCL19, transport processes that are known to contribute to the establishment of spatio temporal chemokine gradients. Two examples are provided that demonstrate the estimation of the governing parameters as well as the underlying uncertainty. This study demonstrates how a synergistic approach between experimental and computational modelling benefits from the Bayesian approach to provide a robust analysis of chemokine transport. It provides a building block for a larger research effort to gain holistic insight and generate novel and testable hypotheses in chemokine biology and leukocyte trafficking.

Betavoltaic power sources based on the conversion of radioisotope energy to electrical power are considered an appealing option for remote applications due to extended period of operation and high energy densities. However, to be competitive with other power sources, their efficiency must be increased. This can be done through optimization of the beta source and selection of the semiconductor absorber. This paper evaluates available on the market and developing wideband gap semiconductors as prospective absorbers with 3H and 63Ni sources. Simulation results indicate that among wide band gap materials 4H-SiC and diamond are two optimal semiconductors due to the combination of good coupling efficiencies with isotope sources and good electronic transport properties. Additionally, having good coupling efficiency, an ultra-wide bandgap, and the capability for both n- and p-type doping, c-BN is a promising material for betavoltaic applications.

GaAs is an attractive material for space solar cells due to it possessing the highest photovoltaic efficiency among semiconductors. However, material vulnerability to radiation damage is a limiting factor, which should be resolved. This can be done through the optimization of solar cell geometry. Specifically, ultra-thin GaAs solar cells possess increased radiation hardness in combination with high specific power (W/kg) making them desirable for space applications. In this research, modeling of single-junction thin GaAs based solar cells with an active device thickness < 1.6 µm is performed to evaluate cell performance at high irradiation levels (1 MeV electrons with a fluence of 1E15 e-/cm2) associated with high energy orbits. The radiation tolerance of two configurations is evaluated; conventional and rear junction (thick emitter) with a backside gold reflective coating. In addition, solar cell structures utilizing n- and p-type base are simulated. The Hovel model, modified to include the photon recycling effect, is used for modeling. The effect of radiation on GaAs electronic properties is counted through degradation of minority carrier lifetime and changes in the carrier concentration. It’s found that conventional n-emitter/p-base and the rear junction with p-type thick emitter configurations with a heavily doped absorber ~5E18 [cm-3] and thickness below 800 nm have increased radiation hardness with a degradation rate

Micro-concentrator photovoltaics (μ-CPV) may provide a cost effective means of producing terrestrial solar power with high area efficiency. By printing CPV onto a transparent substrate, a Si back panel can be used to capture the diffuse sunlight component. Models show that efficiencies above 30% can be achieved even under global normal irradiance (GNI) with a 40% diffuse component. Additionally, the power output of existing installations can be boosted by adding a transparent μ-CPV array on top.To further the development of this technology, we have created a model to analyze μ-CPV array reliability under non-ideal conditions. The adverse effects of partial shading on standard large area panels such as crystalline Silicon (c-Si) are well known, but little investigation has been done on the tolerance of the μ-CPV components. In this article a SPICE simulation is used to analyze the effects of partial shading on a μ-CPV module and evaluate various circuit layouts.

Photoluminescence Excitation Spectroscopy (PLE) is a contactless characterization technique to quantify Shockley-Reed-Hall (SRH) lifetimes and recombination velocities in direct band gap experimental semiconductor materials and devices. It is also useful as to evaluate surface passivation and intermediate fabrication processes, since it can be implemented without the need for development of effective contact technologies. In this paper, we present a novel experimental PLE system for precision-based quantification of the aforementioned parameters as well as a system for which absolute PLE characterization may occur. Absolute PLE measurements can be used to directly calculate VOC for new photovoltaic (PV) material systems and devices. Key system capabilities include a continuous excitation spectrum from 300 nm –1.1 μm, automated characterization, up to 1 nm wavelength resolution (up to 60x higher than prior work), and a reduced ellipsometry requirement for post-processing of data. We utilize a GaAs double heterostructure (DH) and an InP crystalline wafer as calibration standards in comparison with data from an LED-based PLE to demonstrate the validity of the results obtained from this new system.

In this paper, we report findings from a micro CPV module, employing 170 μm GaAs-based 2J CPV cells, assembled on glass substrates using micro-transfer printing. The CPV array uses all-glass lens arrays to focus the light with a geometric concentration ratio of 740 suns, and a bifacial, monocrystalline silicon solar cell behind the substrate to capture the diffuse component of the light. We found that the diffuse capture creates a significant performance boost over CPV alone, and study the role of bifacial capture on the overall performance. The highest combined efficiency with respect to global normal irradiance was 25.4% for the module, measured by outdoor testing in Washington, DC.

The phasic contractions of collecting lymphatic vessels are reduced in strength and occur at diminished frequency when a favorable pressure difference and the resulting antegrade flow create large fluid shear stresses at the luminal surface. This paper describes a minimal phenomenological model of this mechanism that is applied to a previously validated numerical model of a phasically contracting lymphangion. The parameters of the inhibition model are quantitatively matched to observations in isolated segments of rat lymphatic vessel, first for mesenteric lymphatics then for thoracic duct, and outcomes from the numerical model are then qualitatively compared with recent observations in isolated segments of rat thoracic duct.

Lymph nodes (LN) are crucial for immune function, and comprise an important interface between the blood and lymphatic systems. Blood vessels (BV) in LN are highly specialized, featuring high endothelial venules across which most of the resident lymphocytes crossed. Previous measurements of overall lymph and BV flow rates demonstrated that fluid also crosses BV walls, and that this is important for immune function. However, the spatial distribution of the BV in LN has not been quantified to the degree necessary to analyse the distribution of transmural fluid movement. In this study, we seek to quantify the spatial localization of LNBV, and to predict fluid movement across BV walls. MicroCT imaging of murine popliteal LN showed that capillaries were responsible for approximately 75% of the BV wall surface area, and that this was mostly distributed around the periphery of the node. We then modelled blood flow through the BV to obtain spatially resolved hydrostatic pressures, which were then combined with Starling’s law to predict transmural flow. Much of the total 10 nL/min transmural flow (under normal conditions) was concentrated in the periphery, corresponding closely with surface area distribution. These results provide important insights into the inner workings of LN, and provide a basis for further exploration of the role of LN flow patterns in normal and pathological functions.