General-relativistic precession in a black-hole binary.

The general-relativistic phenomenon of spin-induced orbital precession has not yet been observed in strong-field gravity. Gravitational-wave observations of binary black holes (BBHs) are prime candidates, as we expect the astrophysical binary population to contain precessing binaries1,2. Imprints of precession have been investigated in several signals3-5, but no definitive identification of orbital precession has been reported in any of the 84 BBH observations so far5-7 by the Advanced LIGO and Virgo detectors8,9. Here we report the measurement of strong-field precession in the LIGO-Virgo-Kagra gravitational-wave signal GW200129. The binary's orbit precesses at a rate ten orders of magnitude faster than previous weak-field measurements from binary pulsars10-13. We also find that the primary black hole is probably highly spinning. According to current binary population estimates, a GW200129-like signal is extremely unlikely, and therefore presents a direct challenge to many current binary-formation models.

Genotype-by-environment interactions in beef and dairy cattle populations: A review of methodologies and perspectives on research and applications.

Modern livestock production systems are characterized by a greater focus on intensification, involving managing larger numbers of animals to achieve higher productive efficiency and animal health and welfare within herds. Therefore, animal breeding programs need to be strategically designed to select animals that can effectively enhance production performance and animal welfare across a range of environmental conditions. Thus, this review summarizes the main methodologies used for assessing the levels of genotype-by-environment interaction (G × E) in cattle populations. In addition, we explored the importance of integrating genomic and phenotypic information to quantify and account for G × E in breeding programs. An overview of the structure of cattle breeding programs is provided to give insights into the potential outcomes and challenges faced when considering G × E to optimize genetic gains in breeding programs. The role of nutrigenomics and its impact on gene expression related to metabolism in cattle are also discussed, along with an examination of current research findings and their potential implications for future research and practical applications. Out of the 116 studies examined, 60 and 56 focused on beef and dairy cattle, respectively. A total of 83.62% of these studies reported genetic correlations across environmental gradients below 0.80, indicating the presence of G × E. For beef cattle, 69.33%, 24%, 2.67%, 2.67%, and 1.33% of the studies evaluated growth, reproduction, carcass and meat quality, survival, and feed efficiency traits, respectively. By contrast, G × E research in dairy cattle populations predominantly focused on milk yield and milk composition (79.36% of the studies), followed by reproduction and fertility (19.05%), and survival (1.59%) traits. The importance of G × E becomes particularly evident when considering complex traits such as heat tolerance, disease resistance, reproductive performance, and feed efficiency, as highlighted in this review. Genomic models provide a valuable avenue for studying these traits in greater depth, allowing for the identification of candidate genes and metabolic pathways associated with animal fitness, adaptation, and environmental efficiency. Nutrigenetics and nutrigenomics are emerging fields that require extensive investigation to maximize our understanding of gene-nutrient interactions. By studying various transcription factors, we can potentially improve animal metabolism, improving performance, health, and quality of products such as meat and milk.

Photo-Induced Microfluidic Production of Ultrasmall Glyco Gold Nanoparticles.

Ultra-small gold nanoparticles (UAuNPs) are extremely interesting for applications in nanomedicine thanks to their good stability, biocompatibility, long circulation time and efficient clearance pathways. UAuNPs engineered with glycans (Glyco-UAuNPs) emerged as excellent platforms for many applications since the multiple copies of glycans can mimic the multivalent effect of glycoside clusters. Herein, we unravel a straightforward photo-induced synthesis of Glyco-UAuNPs based on a reliable and robust microfluidic approach. The synthesis occurs at room temperature avoiding the use of any further chemical reductant, templating agents or co-solvents. Exploiting 1 H NMR spectroscopy, we showed that the amount of thiol-ligand exposed on the UAuNPs is linearly correlated to the ligand concentration in the initial mixture. The results pave the way towards the development of a programmable synthetic approach, enabling an accurate design of the engineered UAuNPs or smart hybrid nano-systems.

Impact of Dynamical Tides on the Reconstruction of the Neutron Star Equation of State.

Gravitational waves (GWs) from inspiraling neutron stars afford us a unique opportunity to infer the as-of-yet unknown equation of state of cold hadronic matter at supranuclear densities. During the inspiral, the dominant matter effects arise due to the star's response to their companion's tidal field, leaving a characteristic imprint in the emitted GW signal. This unique signature allows us to constrain the cold neutron star equation of state. At GW frequencies above ≳800 Hz, however, subdominant tidal effects known as dynamical tides become important. In this Letter, we demonstrate that neglecting dynamical tidal effects associated with the fundamental (f) mode leads to large systematic biases in the measured tidal deformability of the stars and hence in the inferred neutron star equation of state. Importantly, we find that f-mode dynamical tides will already be relevant for Advanced LIGO's and Virgo's fifth observing run (∼2025)-neglecting dynamical tides can lead to errors on the neutron radius of O(1 km), with dramatic implications for the measurement of the equation of state. Our results demonstrate that the accurate modeling of subdominant tidal effects beyond the adiabatic limit will be crucial to perform accurate measurements of the neutron star equation of state in upcoming GW observations.

Delays during PBMC isolation have a moderate effect on yield, but severly compromise cell viability.

OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) are a versatile material for clinical routine as well as for research projects. However, their isolation via density gradient centrifugation is still time-consuming. When samples are taken beyond usual laboratory handling times, it may sometimes be necessary to pause the isolation process. Our aim was to evaluate the impact of delays up to 48 h after the density gradient centrifugation on PBMC yield, purity and viability. METHODS: PBMCs were isolated from samples of 20 donors, either with BD Vacutainer CPT tubes (CPT) or with the standard Ficoll method. Isolation was paused after initial density gradient centrifugation for 0, 24, or 48 h. PBMC yield (% output/input), purity (% PBMCs/total cells) and viability (% Annexin V-/propidium iodide-) were compared. RESULTS: The yield did not change significantly over time when CPT were used (55%/52%/47%), but did after isolation with the standard method (62%/40%[p<0.0001]/53%[p<0.01]). Purity was marginally affected if CPT were used (95%/93%[p=n.s./92%[p<0.05] vs. 97% for all time points with standard method). Whereas viable PBMCs decreased steadily for CPT isolates (62%/51%[p<0.001]/36%[p<0.0001]), after standard Ficoll gradient isolation, cell apoptosis was more pronounced already after 24 h delay, and viability did not further decrease after 48 h (64%/44%[p<0.0001]/40%[p<0.0001]). CONCLUSIONS: In conclusion, our findings suggest that while post-centrifugation delays ≥24 h might have only a minor effect on cell yield and purity, their impact on cell viability is substantial, even when CPT are used.

Development of epithelial cholinergic chemosensory cells of the urethra and trachea of mice.

Cholinergic chemosensory cells (CCC) are infrequent epithelial cells with immunosensor function, positioned in mucosal epithelia preferentially near body entry sites in mammals including man. Given their adaptive capacity in response to infection and their role in combatting pathogens, we here addressed the time points of their initial emergence as well as their postnatal development from first exposure to environmental microbiota (i.e., birth) to adulthood in urethra and trachea, utilizing choline acetyltransferase (ChAT)-eGFP reporter mice, mice with genetic deletion of MyD88, toll-like receptor-2 (TLR2), TLR4, TLR2/TLR4, and germ-free mice. Appearance of CCC differs between the investigated organs. CCC of the trachea emerge during embryonic development at E18 and expand further after birth. Urethral CCC show gender diversity and appear first at P6-P10 in male and at P11-P20 in female mice. Urethrae and tracheae of MyD88- and TLR-deficient mice showed significantly fewer CCC in all four investigated deficient strains, with the effect being most prominent in the urethra. In germ-free mice, however, CCC numbers were not reduced, indicating that TLR2/4-MyD88 signaling, but not vita-PAMPs, governs CCC development. Collectively, our data show a marked postnatal expansion of CCC populations with distinct organ-specific features, including the relative impact of TLR2/4-MyD88 signaling. Strong dependency on this pathway (urethra) correlates with absence of CCC at birth and gender-specific initial development and expansion dynamics, whereas moderate dependency (trachea) coincides with presence of first CCC at E18 and sex-independent further development.

Constraining the Lensing of Binary Black Holes from Their Stochastic Background.

Gravitational waves (GWs) are subject to gravitational lensing in the same way as electromagnetic radiation. However, to date, no unequivocal observation of a lensed GW transient has been reported. Independently, GW observatories continue to search for the stochastic GW signal that is produced by many transient events at high redshift. We exploit a surprising connection between the lensing of individual transients and limits to the background radiation produced by the unresolved population of binary back hole mergers: we show that it constrains the fraction of individually resolvable lensed binary black holes to less than ∼4×10^{-5} at present sensitivity. We clarify the interpretation of existing, low redshift GW observations (obtained assuming no lensing) in terms of their apparent lensed redshifts and masses and explore constraints from GW observatories at future sensitivity. Based on our results, recent claims of observations of lensed events are statistically disfavored.

Breeding objectives of Brangus cattle in Brazil.

Our goal was to define a breeding objective for Brangus beef cattle in Brazil. Bioeconomic models were produced and used to estimate economic values (EVs). The scenarios simulated were typical full-cycle beef production systems that are used in tropical and subtropical regions. The breeding objective contained pregnancy rate (PR), warm carcass weight (WCW), mature cow weight (MCW), number of nematode eggs per gram of faeces (EPG) and tick count (TICK). Two models were used in series to estimate the EV. A deterministic model was used to simulate effects of PR, WCW and MCW on profitability with a constant parasite load. Subsequently, stochastic models were used to estimate economic values for TICK and EPG as consequences of their environmental effects on weight gains, mortality and health costs. The EV of PR, WCW, MCW, EPG and TICK, was US$1.59, US$2.11, -US$0.24, -US$5.35 and -US$20.88, respectively. Results indicate positive emphasis should be placed on PR (12.49%) and WCW (65.07%) with negative emphasis on MCW (13.92%), EPG (2.77%) and TICK (5.75%). In comparison with the indexes usually used, these results suggest a reformulation in the selection indexes of the beef production system in tropical and subtropical regions in order to obtain greater profitability.

Ten years of chest MRI for patients with cystic fibrosis : Translation from the bench to clinical routine.

BACKGROUND: Despite recent advances in our knowledge about the pathophysiology and treatment of cystic fibrosis (CF), pulmonary involvement remains the most important determinant of morbidity and mortality in patients with CF. Since lung function testing may not be sensitive enough for subclinical disease progression, and because young children may have normal spirometry results over a longer period of time, imaging today plays an increasingly important role in clinical routine and research for the monitoring of CF lung disease. In this regard, chest magnetic resonance imaging (MRI) could serve as a radiation-free modality for structural and functional lung imaging. METHODS: Our research agenda encompassed the entire process of development, implementation, and validation of appropriate chest MRI protocols for use with infant and adult CF patients alike. RESULTS: After establishing a general MRI protocol for state-of-the-art clinical 1.5-T scanners based on the available sequence technology, a semiquantitative scoring system was developed followed by cross-validation of the method against the established modalities of computed tomography, radiography, and lung function testing. Cross-sectional studies were then set up to determine the sensitivity of the method for the interindividual variation of the disease and for changes in disease severity after treatment. Finally, the MRI protocol was implemented at multiple sites to be validated in a multicenter setting. CONCLUSION: After more than a decade, lung MRI has become a valuable tool for monitoring CF in clinical routine application and as an endpoint for clinical studies.

Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats.

AIMS: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl3) on blood pressure, vascular reactivity and oxidative stress. METHODS AND RESULTS: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl3: single dose of AlCl3 (100mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor l-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl3 exposure serum Al levels attained 147.7±25.0µg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. CONCLUSION: AlCl3-acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K+ channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system.

Simple model of complete precessing black-hole-binary gravitational waveforms.

The construction of a model of the gravitational-wave (GW) signal from generic configurations of spinning-black-hole binaries, through inspiral, merger, and ringdown, is one of the most pressing theoretical problems in the buildup to the era of GW astronomy. We present the first such model in the frequency domain, PhenomP, which captures the basic phenomenology of the seven-dimensional parameter space of binary configurations with only three key physical parameters. Two of these (the binary's mass ratio and an effective total spin parallel to the orbital angular momentum, which determines the inspiral rate) define an underlying nonprecessing-binary model. The nonprecessing-binary waveforms are then twisted up with approximate expressions for the precessional motion, which require only one additional physical parameter, an effective precession spin, χ(p). All other parameters (total mass, sky location, orientation and polarization, and initial phase) can be specified trivially. The model is constructed in the frequency domain, which will be essential for efficient GW searches and source measurements. We have tested the model's fidelity for GW applications by comparison against hybrid post-Newtonian-numerical-relativity waveforms at a variety of configurations--although we did not use these numerical simulations in the construction of the model. Our model can be used to develop GW searches, to study the implications for astrophysical measurements, and as a simple conceptual framework to form the basis of generic-binary waveform modeling in the advanced-detector era.

Chapter 2 evolution of burn management in the u.s. Military: impact on nursing.

As the only burn center in the Department of Defense, the U.S. Army Institute of Surgical Research is the primary location for care of service members with burn injuries. The combat operations in Iraq and Afghanistan during the past decade have caused an increase in burn patients. As a result of this increased need, advancements in care were developed. The speed and precision of transporting patients from the battlefield to the burn center has improved over previous conflicts. Technological advancements to support treating complications of burn wound healing were leveraged and are now integrated into daily practice. Clinical decision support systems were developed and deployed at the burn center as well as to combat support hospitals in combat zones. Technology advancements in rehabilitation have allowed more service members to return to active duty or live productive civilian lives. All of these advancements were developed in a patient-centered, interdisciplinary environment where the nurses are integrated throughout the research process and clinical practice with the end goal of healing combat burns in mind.

Tas1R3 Dependent and Independent Recognition of Sugars in the Urethra and the Role of Tuft Cells in this Process.

Increased sugar concentrations on mucosal surfaces display risk factors for infections. This study aims to clarify sugar monitoring in the urethra. Urethral tuft cells (UTC) are known sentinels monitoring the urethral lumen for potentially harmful substances and initiating protective mechanisms. Next-generation sequencing (NGS), RT-PCR, and immunohistochemistry show expression of the taste receptor Tas1R3 in murine UTC, a crucial component of the classical sweet detection pathway. Isolated UTC respond to various sugars with an increase of intracellular [Ca2+]. The Tas1R3 inhibitor gurmarin and Tas1R3 deletion reduces these responses. Utilizing mice lacking UTC, glibenclamide, a K+-ATP channel antagonist, and phlorizin, a SGLT1 inhibitor, reveal an additional Tas1R3 independent sweet detection pathway. Inhibition of both pathways abrogates the sugar responses. Rat cystometry shows that intraurethral application of sucrose and glucose increases detrusor muscle activity Tas1R3 dependently. Sugar monitoring in the urethra occurs via two distinct pathways. A Tas1R3 dependent pathway, exclusive to UTC, and a Tas1R3 independent sweet detection pathway, which can be found both in UTC and in other urethral epithelial cells.

A Nanoplasmonic Assay for Point-of-Care Detection of Mannose-Binding Lectin in Human Serum.

Mannose-binding lectin (MBL) activates the complement system lectin pathway and subsequent inflammatory mechanisms. The incidence and outcome of many human diseases, such as brain ischemia and infections, are associated with and influenced by the activity and serum concentrations of MBL in body fluids. To quantify MBL levels, tests based on ELISA are used, requiring several incubation and washing steps and lengthy turnaround times. Here, we aimed to develop a nanoplasmonic assay for direct MBL detection in human serum at the point of care. Our assay is based on gold nanorods (GNRs) functionalized with mannose (Man-GNRs) via an amphiphilic linker. We experimentally determined the effective amount of sugar linked to the nanorods' surface, resulting in an approximate grafting density of 4 molecules per nm2, and an average number of 11 to 13 MBL molecules binding to a single nanoparticle. The optimal Man-GNRs concentration to achieve the highest sensitivity in MBL detection was 15 µg·mL-1. The specificity of the assay for MBL detection both in simple buffer and in complex pooled human sera was confirmed. Our label-free biosensor is able to detect MBL concentrations as low as 160 ng·mL-1 within 15 min directly in human serum via a one-step reaction and by using a microplate reader. Hence, it forms the basis for a fast, noninvasive, point-of-care assay for diagnostic indications and monitoring of disease and therapy.

Evaluation of the productive and reproductive performance of sexual precocity at different ages in Nellore heifers.

This study aimed to investigate the differences between productive and reproductive performance traits of sexually precocious and non-sexually precocious Nellore heifers and to evaluate the genetic correlation of sexual precocity with traits of economic importance. For this purpose, 300,000 Nellore heifers were evaluated for reproductive traits: heifer pregnancy (HP) at 14 (HP14), 18 (HP18), and 24 (HP24) months; heifer rebreeding (HR); number of progenies up to 53 months (NP53); and probability of the cow remaining in the herd until 76 months with at least 3 progenies (Stay). The growth-related traits evaluated included female yearling weight (YW); average daily gain from weaning to yearling (ADGW-Y); weight at maturity (MW); weaning weight of first progeny (WWprog); and female visual scores at yearling for conformation (Conf), precocity (Prec) and muscling (Musc). The effects of female YW and ADGW-Y in six categories on HP14, HP18, and HP24 were analyzed using Generalized linear mixed models (GLMM). Furthermore, a linear mixed model was used to evaluate the impact of HP on WWprog, MW, and reproductive performance (NP53 and Stay). Genetic correlations of HP evaluated in different months with growth and reproductive traits were estimated using a bivariate animal model. Precocious heifers (HP14) were lighter for YW and MW but had greater ADGW-Y than HP18 and HP24. The probability for HP14, HP18, and HP24 increased as the classes of YW and ADGW-Y increased. However, heifers weighing more than 326 kg had a slight reduction in the probability of becoming pregnant at HP14 and HP18. Precocious heifers (HP14 and HP18) produced their first progeny by 3 % lighter than HP24, although they had a greater NP53. Precocious heifers at 18 months (HP18) were 3 % and 6.8 % more likely to remain in the herd than HP14 and HP24 heifers, respectively. Genetic correlations between growth traits (WW, YW, ADGW-Y, and MW) and heifer pregnancy (HP14, HP18, and HP24) ranged from weak (rg = 0.27 ± 0.05) to moderate (rg = -0.47 ± 0.07). The genetic correlation between HR and HP was stronger for HP24 (0.75) against HP14 (0.58) and HP18 (0.64). Although, the genetic correlation between NP53 and Stay with HP14 was higher (rg = 0.53 and 0.45) than those observed for HP18 (rg = 0.46 and 0.38) and HP24 (rg = 0.35 and 0.39). The genetic correlation estimates between HP and visual scores were moderate and favorable for HP14. Selecting HP14 is beneficial for production systems because it increases the NP53 during the productive life without compromising heifer productivity or reproductive performance. However, attention should be given to improving the HR of heifers who become pregnant early.

Photo-induced microfluidic production of ultrasmall platinum nanoparticles.

We describe here the synthesis of ultrasmall Pt nanoparticles (NPs) obtained by a robust and reliable protocol using UV-Vis photoreduction of a platinum salt precursor, under continuous flow conditions. These ligand-free Pt NPs were rapidly dispersed onto a solid support or stabilized towards aggregation as a colloidal solution by the addition of an appropriate ligand in the reaction mixture. The proposed protocol exploits a microfluidic platform where the Pt4+ precursor is photo-reduced to small Pt0 NPs (1.3 nm) at room temperature in the presence of ethanol, without any additional reducing agent. We apply the protocol to prepare Pt NPs highly dispersed on carbon support (Pt/C) proven to be a very efficient heterogeneous catalyst for both the hydrosilylation of terminal alkynes and hydrogenation of nitroaromatic compounds, selected as model reactions. Furthermore, we exploit the versatility of this microfluidic approach to produce stabilized aqueous/ethanol colloidal solutions of Pt NPs, employing a ligand of choice (e.g., PVP or a thiol-ligand). These colloids offer long-term storage and further ligand modification. We showcase the synthesis of biocompatible glycol-stabilized Pt nanoparticles as an exemplary application.

Genome-wide scans identify biological and metabolic pathways regulating carcass and meat quality traits in beef cattle.

Genome association studies (GWAS) provides knowledge about the genetic architecture of beef-related traits that allow linking the target phenotype to genomic information aiding breeding decision. Thus, the present study aims to uncover the genetic mechanism involved in carcass (REA: rib eye area, BF: backfat thickness, and HCW: hot carcass weight) and meat quality traits (SF: shear-force, MARB: marbling score, and IMF: intramuscular fat content) in Nellore cattle. For this, 6910 young bulls with phenotypic information and 23,859 animals genotyped with 435 k markers were used to perform the weighted single-step GBLUP (WssGBLUP) approach, considering two iterations. The top 10 genomic regions explained 8.13, 11.81, and 9.58% of the additive genetic variance, harboring a total of 119, 143, and 95 positional candidate genes for REA, BF, and HCW, respectively. For meat quality traits, the top 10 windows explained a large proportion of the total genetic variance for SF (14.95%), MARB (17.56%), and IMF (21.41%) surrounding 92, 155, and 111 candidate genes, respectively. Relevant candidate genes (CAST, PLAG1, XKR4, PLAGL2, AQP3/AQP7, MYLK2, WWOX, CARTPT, and PLA2G16) are related to physiological aspects affecting growth, carcass, meat quality, feed intake, and reproductive traits by signaling pathways controlling muscle control, key signal metabolic molecules INS / IGF-1 pathway, lipid metabolism, and adipose tissue development. The GWAS results provided insights into the genetic control of the traits studied and the genes found are potential candidates to be used in the improvement of carcass and meat quality traits.

An Approach to Intersectionally Target Mature Enteroendocrine Cells in the Small Intestine of Mice.

Enteroendocrine cells (EECs) constitute only a small proportion of Villin-1 (Vil1)-expressing intestinal epithelial cells (IECs) of the gastrointestinal tract; yet, in sum, they build the largest endocrine organ of the body, with each of them storing and releasing a distinct set of peptides for the control of feeding behavior, glucose metabolism, and gastrointestinal motility. Like all IEC types, EECs are continuously renewed from intestinal stem cells in the crypt base and terminally differentiate into mature subtypes while moving up the crypt-villus axis. Interestingly, EECs adjust their hormonal secretion according to their migration state as EECs receive altering differentiation signals along the crypt-villus axis and thus undergo functional readaptation. Cell-specific targeting of mature EEC subtypes by specific promoters is challenging because the expression of EEC-derived peptides and their precursors is not limited to EECs but are also found in other organs, such as the brain (e.g., Cck and Sst) as well as in the pancreas (e.g., Sst and Gcg). Here, we describe an intersectional genetic approach that enables cell type-specific targeting of functionally distinct EEC subtypes by combining a newly generated Dre-recombinase expressing mouse line (Vil1-2A-DD-Dre) with multiple existing Cre-recombinase mice and mouse strains with rox and loxP sites flanked stop cassettes for transgene expression. We found that transgene expression in triple-transgenic mice is highly specific in I but not D and L cells in the terminal villi of the small intestine. The targeting of EECs only in terminal villi is due to the integration of a defective 2A separating peptide that, combined with low EEC intrinsic Vil1 expression, restricts our Vil1-2A-DD-Dre mouse line and the intersectional genetic approach described here only applicable for the investigation of mature EEC subpopulations.

Longitudinal Magnetic Resonance Imaging of Changes in Lung Morphology and Perfusion in Children with Cystic Fibrosis From Infancy through Adolescence.

RATIONALE: The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data. OBJECTIVES: To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI). METHODS: 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system. MEASUREMENTS AND MAIN RESULTS: The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001). CONCLUSIONS: This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

Optimizing Virtual Health Technologies Through a Performance-based Readiness Model: Lessons From the Field Deployment of National Emergency Tele-Critical Care Network.

INTRODUCTION: The advancement of the Army's National Emergency Tele-Critical Care Network (NETCCN) and planned evolution to an Intelligent Medical System rest on a digital transformation characterized by the application of analytic rigor anchored and machine learning.The goal is an enduring capability for telecritical care in support of the Nation's warfighters and, more broadly, for emergency response, crisis management, and mass casualty situations as the number and intensity of disasters increase nationwide. That said, technology alone is unlikely to solve the most pressing issues in operational medicine and combat casualty care. MATERIALS AND METHODS: A total performance system (TPS) creates opportunities to address vulnerabilities and overcome barriers to success. As applied during the NETCCN project, the TPS captures the best performance-centric information and know-how, increasing the potential to save lives, improve readiness, and accomplish missions. RESULTS: The purpose of this project was to apply a performance-based readiness model to aid in the evaluation of Army telehealth technologies. Through various user-facing surveys, polls, and reporting techniques, the project aimed to measure the perceived value of telehealth technologies within a sample of the project team member population. By providing a detailed approach to the collection of lessons learned, researchers were able to determine the importance of information and methods versus a focus on technology alone. The use of an emoji-based feedback assessment indicated that most lessons learned were helpful to the project team. CONCLUSIONS: Through the NETCCN TPS, we have been able to address product-related measures, knowledge of product efficacy, project metrics, and many implementation considerations that can be further investigated by setting and engagement type. Through the Technology in Disaster Environments learning accelerator, it was possible to rapidly acquire, process, organize, and disseminate best practices and learnings in near real time, providing a critical feedback and improvement loop.