Modeling of collision-induced excitation and quenching of atomic nitrogen.

Excited atomic nitrogen atoms play an important role in plasma formation in hypersonic shock-waves, as happens during spacecraft reentry and other high velocity vehicle applications. In this study, we have thoroughly studied collision induced excitation associated with two colliding nitrogen atoms in the N(4S), N(2D), and N(2P) states at collision energies up to 6 eV, using time-independent scattering calculations to determine cross sections and temperature-dependent rate coefficients. The calculations are based on potential curves and couplings determined in earlier multireference configuration interaction calculations with large basis sets, and the results are in good agreement with experiments where comparisons are possible. To properly consider the spin-orbit coupling matrix, we have developed a scaling method for treating transitions between different fine-structure components that only require calculations with two coupled states, and with this, we define accurate degeneracy factors for determining cross sections and rate coefficients that include all states. The results indicate that both spin-orbit and derivative coupling effects can play important roles in collisional excitation and quenching, and that although derivative coupling is always much stronger than spin-orbit, there are many transitions where only spin-orbit can contribute. As part of this, we identify two distinct pathways associated with N(2P) relaxation and one Auger-like mechanism leading to two N(2D) that could be important at high temperatures.

Targeting IL-1 controls refractory pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared to psoriasis, atopic dermatitis, healed PRP, and healthy controls, we identified IL-1ß as a key mediator, orchestrating an NF-κB-mediated IL-1ß-CCL20 axis, including activation of CARD14 and NOD2. Treatment of three patients with the IL-1 antagonists anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature with a 50% improvement in skin lesions after 2 to 3 weeks. This transcriptional signature was consistent with in vitro stimulation of keratinocytes with IL-1ß. With the central role of IL-1ß underscoring its potential as a therapeutic target, our findings propose a redefinition of PRP as an autoinflammatory keratinization disorder. Further clinical trials are needed to validate the efficacy of IL-1ß antagonists in PRP.

Mutual information for detecting multi-class biomarkers when integrating multiple bulk or single-cell transcriptomic studies.

Motivation: Biomarker detection plays a pivotal role in biomedical research. Integrating omics studies from multiple cohorts can enhance statistical power, accuracy and robustness of the detection results. However, existing methods for horizontally combining omics studies are mostly designed for two-class scenarios (e.g., cases versus controls) and are not directly applicable for studies with multi-class design (e.g., samples from multiple disease subtypes, treatments, tissues, or cell types). Results: We propose a statistical framework, namely Mutual Information Concordance Analysis (MICA), to detect biomarkers with concordant multi-class expression pattern across multiple omics studies from an information theoretic perspective. Our approach first detects biomarkers with concordant multi-class patterns across partial or all of the omics studies using a global test by mutual information. A post hoc analysis is then performed for each detected biomarkers and identify studies with concordant pattern. Extensive simulations demonstrate improved accuracy and successful false discovery rate control of MICA compared to an existing MCC method. The method is then applied to two practical scenarios: four tissues of mouse metabolism-related transcriptomic studies, and three sources of estrogen treatment expression profiles. Detected biomarkers by MICA show intriguing biological insights and functional annotations. Additionally, we implemented MICA for single-cell RNA-Seq data for tumor progression biomarkers, highlighting critical roles of ribosomal function in the tumor microenvironment of triple-negative breast cancer and underscoring the potential of MICA for detecting novel therapeutic targets. Availability: https://github.com/jianzou75/MICA.

Ultrasonography of Testicular Maturation and Correlation with Body Growth and Semen Evaluation in Beagle Dog Model.

This prospective study investigated the ultrasonographic appearance of the canine testis from birth to adulthood. Eight purpose-bred laboratory Beagle-breed dogs were monitored from 4 to 40 weeks of life. The following parameters were evaluated every two weeks: bodyweight and height, scrotal and testicular volume, ultrasonographically measured testicular volume, echogenicity, heterogeneity, blood-flow score, ratio of the grayscale intensity value of the testis to the capsule, ejaculate volume, motility, viability, and number of spermatozoa. A correlation analysis was carried out between the various measurements obtained. Fertility was achieved in the 36th week of life. The echogenicity of the testicular parenchyma increased with age, and subsequently to the 30th week of life remained constant. The heterogeneity of the testicular parenchyma, as was evaluated by the standard deviation of the values of grayscale intensity of the parenchyma, also increased with age and was >19 at the onset of fertility. The ratio of grayscale intensity of testicular parenchyma had values < 200 at maturity. A colour Doppler evaluation first detected blood flow in the testis in the 22nd week. After the 32nd week, distinct signals were visible. In the 36th week, >80% of the testes imaged had visible vessels. A significant correlation was found between all the evaluation methods. The findings of the study may help clinicians detect the onset of fertility in dogs, especially when semen evaluation is not feasible; however, their applicability in all breeds or individuals might possibly vary due to genetic, physiological, and developmental differences. In summary, the study ultrasonographically explores the testicular maturity in dogs, with the aim to improve clinical assessments and health management in these animals.

The Ability of Physical Performance Measures to Identify Fall Risk in Older Adults Living With Dementia: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine whether physical performance measures commonly used in clinical settings can discriminate fallers from nonfallers and predict falls in older adults with dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Older adults with dementia residing in the community, hospitals, and residential care facilities. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, SPORTDiscus, the Cochrane Library, and the PEDro databases were searched from inception until December 27, 2023 (PROSPERO registration number: CRD42022303670). Retrospective or prospective studies that evaluated the associations between physical performance measures and falls in older adults with dementia were included. A random effects model was used to calculate the standardized mean difference (SMD) and 95% CI for each physical performance measure between fallers and nonfallers. Sensitivity analyses were conducted on the longitudinal studies to determine the ability of physical performance measures to predict future falls. RESULTS: Twenty-eight studies were included in this review (n = 3542). The 5-time chair stand test [SMD = 0.23 (0.01, 0.45)], the Berg Balance Scale [SMD = -0.52 (-0.87, -0.17)], postural sway when standing on the floor [SMD = 0.25 (0.07, 0.43)] and on a foam surface [SMD = 0.45 (0.25, 0.66)], and the Short Physical Performance Battery total score [SMD = -0.46 (-0.66, -0.27)] could discriminate fallers from nonfallers. Sensitivity analyses showed that gait speed could predict future falls in longitudinal cohort studies [SMD = -0.29 (-0.49, -0.08)]. Subgroup analyses showed that gait speed [SMD = -0.21 (-0.38, -0.05)] and the Timed Up and Go test [SMD = 0.54 (0.16, 0.92)] could identify fallers staying in residential care facilities or hospitals. CONCLUSIONS AND IMPLICATIONS: The 5-time chair stand test, the Berg Balance Scale, postural sway when standing on the floor and a foam surface, and the Short Physical Performance Battery can be used to predict falls in older adults with dementia. Gait speed and the Timed Up and Go test can be used to predict falls in institutionalized older adults with dementia. Clinicians are recommended to use these physical performance measures to assess fall risk in older adults with dementia.

Two big bones, one big decision: When to fix bilateral femur fractures.

PURPOSE: For polytrauma patients with bilateral femoral shaft fractures (BFSF), there is currently no consensus on the optimal timing of surgery. This study assesses the impact of early (≤ 24 h) versus delayed (>24 h) definitive fixation on clinical outcomes, especially focusing on concomitant versus staged repair. We hypothesized that early definitive fixation leads to lower mortality and morbidity rates. METHODS: The 2017-2020 Trauma Quality Improvement Program was used to identify patients aged ≥16 years with BFSF who underwent definitive fixation. Early definitive fixation (EDF) was defined as fixation of both femoral shaft fractures within 24 h, delayed definitive fixation (DDF) as fixation of both fractures after 24 h, and early staged fixation (ESF) as fixation of one femur within 24 h and the other femur after 24 h. Propensity score matching and multilevel mixed effects regression models were used to compare groups. RESULTS: 1,118 patients were included, of which 62.8% underwent EDF. Following propensity score matching, 279 balanced pairs were formed. EDF was associated with decreased overall morbidity (12.9% vs 22.6%, p = 0.003), lower rate of deep venous thrombosis (2.2% vs 6.5%, p = 0.012), a shorter ICU LOS (5 vs 7 days, p < 0.001) and a shorter hospital LOS (10 vs 15 days, p < 0.001). When compared to DDF, early staged fixation (ESF) was associated with lower rates of ventilator acquired pneumonia (0.0% vs 4.9%, p = 0.007), but a longer ICU LOS (8 vs 6 days, p = 0.004). Using regression analysis, every 24-hour delay to definitive fixation increased the odds of developing complications by 1.05, postoperative LOS by 10 h and total hospital LOS by 27 h. CONCLUSION: Early definitive fixation (≤ 24 h) is preferred over delayed definitive fixation (>24 h) for patients with bilateral femur shaft fractures when accounting for age, sex, injury characteristics, additional fractures and interventions, and hospital level. Although mortality does not differ, overall morbidity and deep venous thrombosis rates, and length of hospital and intensive care unit stay are significantly lower. When early definitive fixation is not possible, early staged repair seems preferable over delayed definitive fixation.

Emergency general surgery in older adult patients: Factors associated with fragmented care.

BACKGROUND: Care fragmentation has been shown to lead to increased morbidity and mortality. We aimed to explore the factors related to care fragmentation after hospital discharge in geriatric emergency general surgery patients, as well as examine the association between care fragmentation and mortality. METHODS: We designed a retrospective study of the Nationwide Readmissions Database 2019. We included patients ≥65 years old admitted with an emergency general surgery diagnosis who were discharged alive from the index admission. The primary outcome was 90-day care fragmentation, defined as an unplanned readmission to a non-index hospital. Multivariable logistic regression was performed, adjusting for patient and hospital characteristics. RESULTS: A total of 447,027 older adult emergency general surgery patients were included; the main diagnostic category was colorectal (22.6%), and 78.2% of patients underwent non-operative management during the index hospitalization. By 90 days post-discharge, 189,622 (24.3%) patients had an unplanned readmission. Of those readmitted, 20.8% had care fragmentation. The median age of patients with care fragmentation was 76 years, and 53.2% were of female sex. Predictors of care fragmentation were living in rural counties (odds ratio 1.76, 95% confidence interval: 1.57-1.97), living in a low-income ZIP Code, discharge to intermediate care facility (odds ratio 1.28, 95% confidence interval: 1.22-1.33), initial non-operative management (odds ratio 1.17, 95% confidence interval: 1.12-1.23), leaving against medical advice (odds ratio 2.60, 95% confidence interval: 2.29-2.96), and discharge from private investor-owned hospitals (odds ratio 1.18, 95% confidence interval: 1.10-1.27). Care fragmentation was significantly associated with higher mortality. CONCLUSION: The burden of unplanned readmissions in older adult patients who survive an emergency general surgery admission is underestimated, and these patients frequently experience care fragmentation. Future directions should prioritize evaluating the impact of initiatives aimed at alleviating the incidence and complications of care fragmentation in geriatric emergency general surgery patients.

Discharge to Skilled Nursing Facility Is a Risk Factor for Readmission: A Nationwide Propensity-Matched Study.

INTRODUCTION: General surgery procedures place stress on geriatric patients, and postdischarge care options should be evaluated. We compared the association of discharge to a skilled nursing facility (SNF) versus home on patient readmission. METHODS: We retrospectively reviewed the Nationwide Readmission Database (2016-2019) and included patients ≥65 y who underwent a general surgery procedure between January and September. Our primary outcome was 30-d readmissions. Our secondary outcome was predictors of readmission after discharge to an SNF. We performed a 1:1 propensity-matched analysis adjusting for patient demographics and hospital course to compare patients discharged to an SNF with patients discharged home. We performed a sensitivity analysis on patients undergoing emergency procedures and a stepwise regression to identify predictors of readmission. RESULTS: Among 140,056 included patients, 33,916 (24.2%) were discharged to an SNF. In the matched population of 19,763 pairs, 30-d readmission was higher in patients discharged to an SNF. The most common diagnosis at readmission was sepsis, and a greater proportion of patients discharged to an SNF were readmitted for sepsis. In the sensitivity analysis, emergency surgery patients discharged to an SNF had higher 30-d readmission. Higher illness severity during the index admission and living in a small or fringe county of a large metropolitan area were among the predictors of readmission in patients discharged to an SNF, while high household income was protective. CONCLUSIONS: Discharge to an SNF compared to patients discharged home was associated with a higher readmission. Future studies need to identify the patient and facility factors responsible for this disparity.

Lost in transition: Impact of interhospital transfer on outcomes after emergency general surgery in the older adult population.

BACKGROUND: Emergency general surgery performed among patients over 65 years of age represents a particularly high-risk population. Although interhospital transfer has been linked to higher mortality in emergency general surgery patients, its impact on outcomes in the geriatric population remains uncertain. We aimed to establish the effect of interhospital transfer on postoperative outcomes in geriatric emergency general surgery patients. METHODS: Emergency general surgery patients 65 years and older were identified with American College of Surgeons National Surgical Quality Improvement Program 2013 to 2019. Patients were categorized based on admission source as either directly admitted or transferred from an outside hospital inpatient unit or emergency department. The primary outcomes evaluated were in-hospital mortality, 30-day mortality, and overall morbidity. Propensity score matching was used to control for confounders, including age, race, comorbidities, and preoperative conditions. Kaplan-Meier survival analysis and the log-rank test were used to compare 30-day survival in the matched cohort. RESULTS: Among the 88,424 patients identified, 13,872 (15.7%) were transfer patients. The median age was 74, and 53% were of female sex. Transfer patients had higher rates of comorbidities and preoperative conditions, including a higher prevalence of preoperative sepsis (21.8% vs 19.3%, P < .001) and ventilator dependence (6.4% vs 2.6%, P < .001). After propensity score-matched analysis, transferred patients exhibited higher rates of in-hospital mortality, 30-day mortality, and overall morbidity. Transfer patients were also less likely to be discharged home and more likely to be discharged to an acute care facility. Kaplan-Meier survival analysis confirmed a poorer 30-day survival in transferred patients. CONCLUSION: Interhospital transfer independently contributed to overall mortality and morbidity amongst geriatric emergency general surgery patients. Further investigation into improved coordination between hospitals, tailored care plans, and comprehensive risk assessments are needed to help mitigate the observed differences in outcomes.

EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with underdevelopment of left-sided heart structures. While previously uniformly fatal, surgical advances now provide highly effective palliation that allows most HLHS patients to survive their critical CHD. Nevertheless, there remains high morbidity and mortality with high risk of heart failure. As hemodynamic compromise from restricted aortic blood flow has been suggested to underlie the poor LV growth, this suggests the possibility of prenatal fetal intervention to recover LV growth. As such interventions have yielded ambiguous results, the optimization of therapy will require more mechanistic insights into the developmental etiology for HLHS. Clinical studies have shown high heritability for HLHS, with an oligogenic etiology indicated in conjunction with genetic heterogeneity. This is corroborated with the recent recovery of mutant mice with HLHS. With availability-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from HLHS mice and patients, new insights have emerged into the cellular and molecular etiology for the LV hypoplasia in HLHS. Cell proliferation defects were observed in conjunction with metaphase arrest and the disturbance of Hippo-YAP signaling. The left-sided restriction of the ventricular hypoplasia may result from epigenetic perturbation of pathways regulating left-right patterning. These findings suggest new avenues for fetal interventions with therapies using existing drugs that target the Hippo-YAP pathway and/or modulate epigenetic regulation.

Nurses' Perspectives on the Proposed Seclusion Elimination in Mental Health Wards.

Managing consumers with challenging behaviours by way of secluding them has been practiced for centuries. Many countries have attempted to eliminate seclusion but with very limited success. The Victorian government in Australia has embarked on a plan to stop seclusion within the coming 10 years. A qualitative research design using a purposive cluster sampling technique was utilised to understand nurses' perceptions on attempts to eliminate seclusions in acute wards. Semi-structured interviews and a thematic analysis were used to reveal participants' perceptions. Analysis revealed six themes: personal views, staff skills/resources, safety concerns, stakeholders' influence, doubt about elimination and participants' recommendations. Participants were doubtful of seclusion elimination success if there were no major improvements in nurse security, infrastructure, funding and staffing. Further research is required to establish and develop effective alternatives to seclusion.

The PP2A regulatory subunit PPP2R2A controls NAD+ biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.

The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD+ biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. NR inhibits murine Th17 and promotes Treg cell differentiation, in vitro, by PΑRylating histone H1.2 and causing its reduced occupancy in the Foxp3 loci and increased occupancy in the Il17a loci, leading to increased Foxp3 and decreased Il17a transcription. NR treatment suppresses disease in MRL.lpr mice and restores NAD+-dependent poly [ADP-ribose] polymerase 1 (PARP1) activity in CD4 T cells from patients with systemic lupus erythematosus (SLE), while reducing interferon (IFN)-γ and interleukin (IL)-17 production. We conclude that PPP2R2A controls the level of NAD+ through the NR-directed salvage pathway and promotes systemic autoimmunity. Translationally, NR suppresses lupus nephritis in mice and limits the production of proinflammatory cytokines by SLE T cells.

Outcomes of Combined Opioids and Benzodiazepines Consumption in Elderly Trauma: A Retrospective Cohort Study.

BACKGROUND: Acute substance intoxication is associated with traumatic injury and worse hospital outcomes. The objective of this study was to evaluate the association between simultaneous opioids and benzodiazepines (OB) use and hospital outcomes in elderly trauma patients. METHODS: We performed a retrospective analysis using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) 2017 database. We included trauma patients (age ≥ 65 years) examined by urine toxicology within 24 hours of presentation. The primary outcome was in-hospital mortality. Secondary outcomes included hospital and ICU lengths of stay (HLOS AND ICULOS), in-hospital complications (eg, ventilator-associated pneumonia), unplanned intubation, and duration of mechanical ventilation. Patients were stratified being both positive for opioids and benzodiazepines (OB+) or not (OB-) based on having positive or negative drug screen for both drugs, respectively. A 1:1 propensity score matching was performed controlling for demographics (eg, age and sex), comorbidities (eg, alcoholism), and injury characteristics. RESULTS: Of 77,311 tested patients, 849 OB+ were matched to OB- patients. Compared to OB- group, OB+ patients were more likely to have unplanned intubation (26 [3.1%] vs 8 [0.9%], P = 0.002) and had prolonged HLOS (≥2 days: 683 [84.0%] vs 625 [77.8%], P = 0.002). There were no differences in all other outcomes (P > 0.05). CONCLUSIONS: The OB intake is associated with higher incidence of unplanned intubation and longer HLOS in elderly trauma patients. Early identification of elderly trauma patient with OB+ can help provide necessary pharmacologic and behavioral interventions to treat their substance use and potentially improve outcomes.

The effect of a dynamic lighting schedule on neurobehavioral performance during a 45-day simulated space mission.

Study Objectives: We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days. Methods: Sixteen crewmembers (37.4 ±â€…6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (~6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) and blue-depleted (~3000-4000 K; L1: 21, L2: 2 melEDI lux) 3 hours before bed. In the standard lighting schedule (SLS; n = 8), lighting remained constant (~4500K; L1: 284, L2 62 melEDI lux). Effects of lighting condition (DLS/SLS), sleep condition (5/8 hours), time into mission, and their interactions, and time awake on PVT performance were analyzed using generalized linear mixed models. Results: The DLS was associated with fewer attentional lapses (reaction time [RT] > 500 milliseconds) compared to SLS. Lapses, mean RT, and 10% fastest/slowest RTs were worse following 5 compared to 8 hours of sleep but not between lighting conditions. There was an effect of time into mission on RTs, likely due to sleep loss. Overall performance differed by time of day, with longer RTs at the beginning and end of the day. There were more lapses and slower RTs in the afternoon in the SLS compared to the DLS condition. Conclusions: Future missions should incorporate DLS to enhance circadian alignment and performance. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.

Establishment of Cardiac Laterality.

Formation of the vertebrate heart with its complex arterial and venous connections is critically dependent on patterning of the left-right axis during early embryonic development. Abnormalities in left-right patterning can lead to a variety of complex life-threatening congenital heart defects. A highly conserved pathway responsible for left-right axis specification has been uncovered. This pathway involves initial asymmetric activation of a nodal signaling cascade at the embryonic node, followed by its propagation to the left lateral plate mesoderm and activation of left-sided expression of the Pitx2 transcription factor specifying visceral organ asymmetry. Intriguingly, recent work suggests that cardiac laterality is encoded by intrinsic cell and tissue chirality independent of Nodal signaling. Thus, Nodal signaling may be superimposed on this intrinsic chirality, providing additional instructive cues to pattern cardiac situs. The impact of intrinsic chirality and the perturbation of left-right patterning on myofiber organization and cardiac function warrants further investigation. We summarize recent insights gained from studies in animal models and also some human clinical studies in a brief overview of the complex processes regulating cardiac asymmetry and their impact on cardiac function and the pathogenesis of congenital heart defects.

Molecular Pathways and Animal Models of Defects in Situs.

Left-right patterning is among the least well understood of the three axes defining the body plan, and yet it is no less important, with left-right patterning defects causing structural birth defects with high morbidity and mortality, such as complex congenital heart disease, biliary atresia, or intestinal malrotation. The cell signaling pathways governing left-right asymmetry are highly conserved and involve multiple components of the TGF-ß superfamily of cell signaling molecules. Central to left-right patterning is the differential activation of Nodal on the left, and BMP signaling on the right. In addition, a plethora of other cell signaling pathways including Shh, FGF, and Notch also contribute to the regulation of left-right patterning. In vertebrate embryos such as the mouse, frog, or zebrafish, the specification of left-right identity requires the left-right organizer (LRO) containing cells with motile and primary cilia that mediate the left-sided propagation of Nodal signaling, followed by left-sided activation of Lefty and then Pitx2, a transcription factor that specifies visceral organ asymmetry. While this overall scheme is well conserved, there are striking species differences, including the finding that motile cilia do not play a role in left-right patterning in some vertebrates. Surprisingly, the direction of heart looping, one of the first signs of organ left-right asymmetry, was recently shown to be specified by intrinsic cell chirality, not Nodal signaling, possibly a reflection of the early origin of Nodal signaling in radially symmetric organisms. How this intrinsic chirality interacts with downstream molecular pathways regulating visceral organ asymmetry will need to be further investigated to elucidate how disturbance in left-right patterning may contribute to complex CHD.

A Lumped-Parameter Model of the Cardiovascular System Response for Evaluating Automated Fluid Resuscitation Systems.

Physiological closed-loop controlled (PCLC) medical devices, such as those designed for blood pressure regulation, can be tested for safety and efficacy in real-world clinical settings. However, relying solely on limited animal and clinical studies may not capture the diverse range of physiological conditions. Credible mathematical models can complement these studies by allowing the testing of the device against simulated patient scenarios. This research involves the development and validation of a low-order lumped-parameter mathematical model of the cardiovascular system's response to fluid perturbation. The model takes rates of hemorrhage and fluid infusion as inputs and provides hematocrit and blood volume, heart rate, stroke volume, cardiac output and mean arterial blood pressure as outputs. The model was calibrated using data from 27 sheep subjects, and its predictive capability was evaluated through a leave-one-out cross-validation procedure, followed by independent validation using 12 swine subjects. Our findings showed small model calibration error against the training dataset, with the normalized root-mean-square error (NRMSE) less than 10% across all variables. The mathematical model and virtual patient cohort generation tool demonstrated a high level of predictive capability and successfully generated a sufficient number of subjects that closely resembled the test dataset. The average NRMSE for the best virtual subject, across two distinct samples of virtual subjects, was below 12.7% and 11.9% for the leave-one-out cross-validation and independent validation dataset. These findings suggest that the model and virtual cohort generator are suitable for simulating patient populations under fluid perturbation, indicating their potential value in PCLC medical device evaluation.

The art of establishing mineral tolerances of dogs and cats.

For over six decades, nutritional science has provided well-developed, peer-reviewed nutrient recommendations to support the health of dogs and cats. These guidelines are updated based on new scientifically valid research and appropriate peer-review. Recent regulatory and scientific positions around health issues have resulted in strong opinions and desires for rapid regulatory action surrounding mineral nutrition, but with limited and conflicting scientific evidence. Pet Food Institute nutrition experts have come together to jointly author an article on the complexities of establishing mineral tolerances of dogs and cats to illustrate the limitations in defining mineral tolerances. This discussion covers how mineral requirements were determined, including the opportunities and pitfalls encountered. Scientific councils must review and clarify any proposed changes in conducting mineral nutrition research that might impact complete and balanced foods and surrounding regulations. It is important to clarify the multiple issues in mineral nutrition research and the necessity for thorough evaluation of data while avoiding arbitrary and potentially harmful guidelines.

Dogs and cats are living longer and healthier lives due, in part, to the scientific development of nutritional information. This information has allowed the building of many new types of foods, treats, and supplements that promote life, health, and enjoyment by the pet. There are several organizations that have provided helpful reviews of nutritional data through scientific councils that help identify safe and healthy criteria for all pet food products. These are readily available for those who want to learn more about pet nutrition. For many nutrients, there is a large database of information to help build products. Nutrients that are called macro- or micro-/trace minerals (e.g., sodium, potassium, zinc, copper, etc.) often have more limited information. Recently, strong opinions about pet health as related to mineral nutrition have been shared and robustly communicated without adequate scientific research to support the hypotheses. This has led to misinformation, concerns, and fear. To safeguard the health of companion animals and provide assistance to regulatory bodies regarding the nutritional welfare of dogs and cats, scientific panels have come together from industry, government, and academia to review, approve, and challenge nutritional guidelines. This overview provides the reader context into the rigor needed to establish safe mineral tolerances for dogs and cats.

The Open Abdomen After Intra-abdominal Contamination in Emergency General Surgery.

INTRODUCTION: Delayed fascial closure (DFC) is an increasingly utilized technique in emergency general surgery (EGS), despite a lack of data regarding its benefits. We aimed to compare the clinical outcomes of DFC versus immediate fascial closure (IFC) in EGS patients with intra-abdominal contamination. METHODS: This retrospective study was conducted using the 2013-2020 American College of Surgeons National Surgical Quality Improvement Program database. Adult EGS patients who underwent an exploratory laparotomy with intra-abdominal contamination [wound classification III (contaminated) or IV (dirty)] were included. Patients with agreed upon indications for DFC were excluded. A propensity-matched analysis was performed. The primary outcome was 30-d mortality. RESULTS: We identified 36,974 eligible patients. 16.8% underwent DFC, of which 51.7% were female, and the median age was 64 y. After matching, there were 6213 pairs. DFC was associated with a higher risk of mortality (15.8% versus 14.2%, P = 0.016), pneumonia (11.7% versus 10.1%, P = 0.007), pulmonary embolism (1.9% versus 1.6%, P = 0.03), and longer hospital stay (11 versus 10 d, P < 0.001). No significant differences in postoperative sepsis and deep surgical site infection rates between the two groups were observed. Subgroup analyses by preoperative diagnosis (diverticulitis, perforation, and undifferentiated sepsis) showed that DFC was associated with longer hospital stay in all subgroups, with a higher mortality rate in patients with diverticulitis (8.1% versus 6.1%, P = 0.027). CONCLUSIONS: In the presence of intra-abdominal contamination, DFC is associated with longer hospital stay and higher rates of mortality and morbidity. DFC was not associated with decreased risk of infectious complications. Further studies are needed to clearly define the indications of DFC.