Overcoming the pitfalls of categorizing continuous variables in ecology, evolution and behaviour.

Many variables in biological research-from body size to life-history timing to environmental characteristics-are measured continuously (e.g. body mass in kilograms) but analysed as categories (e.g. large versus small), which can lower statistical power and change interpretation. We conducted a mini-review of 72 recent publications in six popular ecology, evolution and behaviour journals to quantify the prevalence of categorization. We then summarized commonly categorized metrics and simulated a dataset to demonstrate the drawbacks of categorization using common variables and realistic examples. We show that categorizing continuous variables is common (31% of publications reviewed). We also underscore that predictor variables can and should be collected and analysed continuously. Finally, we provide recommendations on how to keep variables continuous throughout the entire scientific process. Together, these pieces comprise an actionable guide to increasing statistical power and facilitating large synthesis studies by simply leaving continuous variables alone. Overcoming the pitfalls of categorizing continuous variables will allow ecologists, ethologists and evolutionary biologists to continue making trustworthy conclusions about natural processes, along with predictions about their responses to climate change and other environmental contexts.

Race, Ethnicity, and Gender Disparities in Acute Myocardial Infarction.

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States. Despite advancements in medical care, there remain persistent racial, ethnic, and gender disparity in the diagnosis, treatment, and prognosis of individuals with cardiovascular disease. In this review we seek to discuss differences in pathophysiology, clinical course, and risk profiles in the management and outcomes of acute myocardial infarction and related high-risk states. We also seek to highlight the demographic and psychosocial inequities that cause disparities in acute cardiovascular care.

Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia.

Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. Despite this, we find that MPAL blasts express a shared stem cell-like transcriptional profile indicative of high differentiation potential. Patients with the highest differentiation potential demonstrate inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in the most stem-like MPAL cells, is applicable to bulk RNA sequencing data and is predictive of survival in an independent patient cohort, suggesting a potential strategy for clinical risk stratification.

Acute brain injury risk prediction models in venoarterial extracorporeal membrane oxygenation patients with tree-based machine learning: An Extracorporeal Life Support Organization Registry analysis.

Objective: We aimed to determine if machine learning can predict acute brain injury and to identify modifiable risk factors for acute brain injury in patients receiving venoarterial extracorporeal membrane oxygenation. Methods: We included adults (age ≥18 years) receiving venoarterial extracorporeal membrane oxygenation or extracorporeal cardiopulmonary resuscitation in the Extracorporeal Life Support Organization Registry (2009-2021). Our primary outcome was acute brain injury: central nervous system ischemia, intracranial hemorrhage, brain death, and seizures. We used Random Forest, CatBoost, LightGBM, and XGBoost machine learning algorithms (10-fold leave-1-out cross-validation) to predict and identify features most important for acute brain injury. We extracted 65 total features: demographics, pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation laboratory values, and pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation settings. Results: Of 35,855 patients receiving venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation) (median age of 57.8 years, 66% were male), 7.7% (n = 2769) experienced acute brain injury. In venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation), the area under the receiver operator characteristic curves to predict acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.67, 0.67, and 0.62, respectively. The true-positive, true-negative, false-positive, false-negative, positive, and negative predictive values were 33%, 88%, 12%, 67%, 18%, and 94%, respectively, for acute brain injury. Longer extracorporeal membrane oxygenation duration, higher 24-hour extracorporeal membrane oxygenation pump flow, and higher on-extracorporeal membrane oxygenation partial pressure of oxygen were associated with acute brain injury. Of 10,775 patients receiving extracorporeal cardiopulmonary resuscitation (median age of 57.1 years, 68% were male), 16.5% (n = 1787) experienced acute brain injury. The area under the receiver operator characteristic curves for acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.72, 0.73, and 0.69, respectively. Longer extracorporeal membrane oxygenation duration, older age, and higher 24-hour extracorporeal membrane oxygenation pump flow were associated with acute brain injury. Conclusions: In the largest study predicting neurological complications with machine learning in extracorporeal membrane oxygenation, longer extracorporeal membrane oxygenation duration and higher 24-hour pump flow were associated with acute brain injury in nonextracorporeal cardiopulmonary resuscitation and extracorporeal cardiopulmonary resuscitation venoarterial extracorporeal membrane oxygenation.

Designing Survey-Based Mobile Interfaces for Rural Patients With Cancer Using Apple's ResearchKit and CareKit: Usability Study.

BACKGROUND: Despite the increased accessibility and availability of technology in recent years, equality and access to health-related technology remain limited to some demographics. In particular, patients who are older or from rural communities represent a large segment of people who are currently underusing mobile health (mHealth) solutions. System usability continues to hinder mHealth adoption among users with nontraditional digital literacy. OBJECTIVE: This study aims to investigate if state-of-the-art mobile app interfaces from open-source libraries provide sufficient usability for rural patients with cancer, with minimal design changes and forgoing the co-design process. METHODS: We developed Assuage (Network Reconnaissance Lab) as a research platform for any mHealth study. We conducted a pilot study using Assuage to assess the usability of 4 mobile user interfaces (UIs) based on open-source libraries from Apple's ResearchKit and CareKit. These UIs varied in complexity for reporting distress symptoms. Patients with cancer were recruited at the Markey Cancer Center, and all research procedures were conducted in person. Participants completed the distress assessment using a randomly selected UI in Assuage with little to no assistance. Data were collected on participant age, location, mobile app use, and familiarity with mHealth apps. Participants rated usability with the System Usability Scale (SUS), and usability issues were documented and compared. A one-way ANOVA was used to compare the effect of the UIs on the SUS scores. RESULTS: We recruited 30 current or postsurgery patients with cancer for this pilot study. Most participants were aged >50 years (24/30, 80%), from rural areas (25/30, 83%), had up to a high school education (19/30, 63%), and were unfamiliar with mHealth apps (21/30, 70%). General mobile app use was split, with 43% (14/30) of the patients not regularly using mobile apps. The mean SUS score across the UIs was 75.8 (SD 22.2), with UI 3 and UI 4 achieving an SUS score ≥80, meeting the industry standard for good usability of 80. Critical usability issues were related to data input and navigation with touch devices, such as scale-format questions, vertical scrolling, and traversing multiple screens. CONCLUSIONS: The findings from this study show that most patients with cancer (20/30, 67%) who participated in this study rated the different interfaces of Assuage as above-average usability (SUS score >68). This suggests that Apple's ResearchKit and CareKit libraries can provide usable UIs for older and rural users with minimal interface alterations. When resources are limited, the design stage can be simplified by omitting the co-design process while preserving suitable usability for users with nontraditional technical proficiency. Usability comparable to industry standards can be achieved by considering heuristics for interface and electronic survey design, specifically how to segment and navigate surveys, present important interface elements, and signal gestural interactions.

Utilization of inpatient palliative care services in cardiac arrest complicating acute pulmonary embolism.

Introduction: The role of palliative care services in patients with cardiac arrest complicating acute pulmonary embolism has been infrequently studied. Methods: All adult admissions with pulmonary embolism complicating cardiac arrest were identified using the National Inpatient Sample (2016-2020). The primary outcome of interest was the utilization of palliative care services. Secondary outcomes included predictors of palliative care utilization and its association of with in-hospital mortality, do-not-resuscitate status, discharge disposition, length of stay, and total hospital charges. Multivariable regression analysis was used to adjust for confounding. Results: Between 01/01/2016 and 12/31/2020, of the 7,320 admissions with pulmonary embolism complicating cardiac arrest, 1229 (16.8 %) received palliative care services. Admissions receiving palliative care were on average older (68.1 ± 0.9 vs. 63.2 ± 0.4 years) and with higher baseline comorbidity (Elixhauser index 6.3 ± 0.1 vs 5.6 ± 0.6) (all p < 0.001). Additionally, this cohort had higher rates of non-cardiac organ failure (respiratory, renal, hepatic, and neurological) and invasive mechanical ventilation (all p < 0.05). Catheter-directed therapy was used less frequently in the cohort receiving palliative care, (2.8 % vs 7.9 %; p < 0.001) whereas the rates of systemic thrombolysis, mechanical and surgical thrombectomy were comparable. The cohort receiving palliative care services had higher in-hospital mortality (85.7 % vs. 69.1 %; adjusted odds ratio 2.20 [95 % CI 1.41-3.42]; p < 0.001). This cohort also had higher rates of do-not-resuscitate status and fewer discharges to home, but comparable hospitalization costs and length of hospital stay. Conclusions: Palliative care services are used in only 16.8 % of admissions with cardiac arrest complicating pulmonary embolism with significant differences in the populations, suggestive of selective consultation.

Observed declines in body size have differential effects on survival and recruitment, but no effect on population growth in tropical birds.

Declines in body size can be an advantageous physiological response to warming temperatures, or a result of physiological and nutritional stress. Either way, studies often assume that these climate-induced trait changes have important implications for fitness and demography. We leveraged almost three decades of capture-mark-recapture data of 51 bird species in Panama to examine if body size has changed through time, how sensitive body size is to changes in weather, and if body size impacts population demography. We evaluated two metrics of body size, structural size (wing length), and body condition (residual body mass). Over the study, wing length changed in varying directions for 88% of species (23 decrease, 22 increase), but the effects were weak, and change was only significant for two species. Conversely, body condition declined for 88% of species (45), effects were stronger, and that change was significant for 22% of species (11). This suggests that nutritional stress is likely the cause of changes in body size, not an adaptive response to warming. Precipitation metrics impacted body condition across three of our four feeding guilds, while wing length was only impacted by weather metrics for two guilds. This suggests that body condition is more sensitive to change in weather metrics compared to wing length. Lastly, we found that the impact of changes in body size on survival and recruitment was variable across species, but these relationships were in the opposite direction, ultimately resulting in no change in population growth for all but one species. Thus, while different stages (adult survival and recruitment) of populations may be impacted by body size, populations appear to be buffered from changes. The lack of an effect on population growth rate suggests that populations may be more resilient to changes in body size, with implications for population persistence under expected climate change.

Invasive Mechanical Ventilation Is Associated with Worse Right Ventricular Strain in Acute Respiratory Failure Patients.

Right ventricular (RV) dysfunction is associated with poor prognosis in acute respiratory failure (ARF). Our study evaluates the efficacy of RV strain in detecting RV dysfunction in ARF patients requiring invasive mechanical ventilation (IMV) compared to tricuspid annular plane systolic excursion (TAPSE). In this retrospective study involving 376 patients diagnosed with ARF and requiring IMV, we extracted clinical and outcome data from patient records. RV global longitudinal strain (RVGLS), free wall longitudinal strain (FWLS), and TAPSE were measured retrospectively using speckle tracking echocardiography (STE) and traditional echocardiography, respectively. We divided the cohort into three groups: TTE during IMV (TTE-IMV, 223 patients), before IMV (TTE-bIMV, 68 patients), and after IMV (TTE-aIMV, 85 patients). Multivariable regression analysis, adjusted for covariates, revealed significantly higher RVGLS and FWLS in the groups not on IMV at the time of TTE compared to the TTE-IMV group. Specifically, the TTE-bIMV group showed higher RVGLS (ß = 7.28, 95% CI 5.07, 9.48) and FWLS (ß = 5.83, 95% CI 3.36, 8.31), while the TTE-aIMV group exhibited higher RVGLS (ß = 9.39, 95% CI 6.10, 12.69) and FWLS (ß = 7.54, 95% CI 4.83, 10.24). TAPSE did not reveal any significant differences across the groups. Our study suggests an association between IMV and lower RVGLS and FWLS in ARF patients, indicating that IMV itself may contribute to RV dysfunction. RVGLS and FWLS appear to be more sensitive than TAPSE in detecting changes in RV function that were previously subclinical in patients on IMV. Prospective studies with TTE before, during, and after IMV are necessary to assess the primary driver of RV dysfunction and to prognosticate STE-detected RV dysfunction in this population.

Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis. Although our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease.

Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle.

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p < 0.0001) and GLO1 activity by 42 ± 0.12 % (p = 0.0150). KD of NAMPT also resulted in attenuation of GLO1 protein (28 ± 0.069 %, p = 0.003), activity (67 ± 0.09 %, p = 0.011) and transcripts (50 ± 0.13 %, p = 0.049). Neither the provision of the NAD+ precursors NR nor NMN were able to prevent this attenuation in GLO1 protein. However, NR did augment GLO1 specific activity (p = 0.022 vs NAMPT KD). These perturbations did not alter GLO1 acetylation status. SIRT1, SIRT2 and NAMPT protein levels were all equivocal in skeletal muscle tissue biopsies from individuals with obesity and lean individuals. These data implicate NAD+-dependent regulation of GLO1 in skeletal muscle independent of altered GLO1 acetylation and provide rationale for exploring NR supplementation to rescue attenuated GLO1 abundance and activity in conditions such as obesity.

Impact of Joint Laxity on 2-Year KOOS Outcomes of Posterior Stabilized Total Knee Arthroplasty.

The objective of this study was to determine relationships between intraoperative posterior cruciate ligament (PCL) sacrificing posterior stabilized (PS) total knee arthroplasty (TKA) laxity measurements throughout flexion and patient outcomes at 2 years post-TKA and to define clinically relevant laxity thresholds to optimize patient outcomes.In a single-surgeon study, PCL sacrificing TKA using a robotics-assisted platform with a digital joint tensioning device was performed in 115 knees in 115 patients. Final intraoperative joint laxity was recorded, and 2-year Knee Injury and Osteoarthritis Outcome Scores (KOOSs) were obtained. A Simulated Annealing optimization algorithm was used to identify medial and lateral laxity windows which maximized the 2-year KOOS pain score. Wilcoxon nonparametric tests were used to compare outcomes between groups.Significant associations were found between intraoperative joint laxity and 2-year KOOS pain outcomes throughout flexion. Clinically relevant laxity windows were defined medially and laterally in mid-flexion and flexion for improved outcomes, whereas only a lateral laxity window could be defined in extension. When all laxity windows were satisfied, a 14.5-KOOS point improvement was found (97.2 vs. 77.8, p = 0.0060) compared to knees which did not satisfy any window. Improvements in Activities of Daily Living (Δ8.8, p = 0.0143), Sports (Δ22.5, p = 0.0108), and Quality of Life (Δ18.7, p = 0.0011) KOOS subscores were also found in knees which satisfied all windows versus 0-1 window.Intraoperative joint laxity is associated with postoperative outcomes in a PS knee design, wherein patients balanced within identified laxity targets reported improved outcomes over those that did not. Clinically significant thresholds were defined and were predominately found in mid-flexion and flexion for medial and lateral laxity. When target windows were combined further improved outcomes were identified.

Sexual Identity Differences in Chronic Pain: Results from the 2019 to 2021 National Health Interview Survey.

INTRODUCTION: Chronic pain has been highlighted as an important public health and clinical health issue. The prevalence of chronic pain has been increasing, with notable disparities for many minoritized populations. However, evidence regarding sexual minoritized populations and chronic pain is lacking. Therefore, the purpose of this study is to compare the prevalence of chronic pain among men and women by sexual identity. METHODS: Data from the 2019 to 2021 National Health Interview Survey (n=78,686), a population-based public health surveillance system were analyzed in 2023-2024. This included 592 lesbian/gay and 952 bisexual women as well as 868 gay and 317 bisexual men. Chronic pain measures included frequency, amount of pain, pain limiting activities, and pain affecting family and others. Covariates included age, race/ethnicity, relationship status, education attainment, income, and employment status. RESULTS: After adjusting for covariates, significantly (p<0.05) more gay/lesbian (26.7%) and bisexual (31.6%) women reported experiencing chronic pain "most days or everyday" than straight women (21.7%). More bisexual women reported chronic pain as well as negative impacts in their life due to chronic pain than straight women. More bisexual men also reported experiencing chronic pain "most days or everyday" compared to straight men (26.1% versus 19.6%), although no differences were found for other aspects of pain. CONCLUSIONS: Sexual minoritized populations have a greater burden of chronic pain that should be considered in moving forward in pain work. Future work in this area is needed to understand why these disparities exist and how best to provide care and treatment to those affected.

Extrapulmonary manifestations of pulmonary arterial hypertension.

INTRODUCTION: Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH. AREAS COVERED: A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers. EXPERT OPINION: Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.

Habitat use of Amazonian birds varies by age and foraging guild along a disturbance gradient.

Patterns of habitat use directly influence a species' fitness, yet for many species an individual's age can influence patterns of habitat use. However, in tropical rainforests, which host the greatest terrestrial species diversity, little is known about how age classes of different species use different adjacent habitats of varying quality. We use long-term mist net data from the Amazon rainforest to assess patterns of habitat use among adult, adolescent (teenage) and young understory birds in forest fragments, primary and secondary forest at the Biological Dynamics of Forest Fragments Project in Brazil. Insectivore adults were most common in primary forest, adolescents were equally likely in primary and secondary forest, and all ages were the least common in forest fragments. In contrast to insectivores, frugivores and omnivores showed no differences among all three habitat types. Our results illustrate potential ideal despotic distributions among breeding populations of some guilds of understory birds where adult insectivores may competitively exclude adolescent individuals from primary forest. Secondary forest recovery appears to hold promise as a breeding habitat for frugivore and omnivore species but only as a pre-breeding habitat for insectivores, but as the forest ages, the demographic structure of bird populations should match that of primary forest.

Inhomogeneous high temperature melting and decoupling of charge density waves in spin-triplet superconductor UTe2.

Charge, spin and Cooper-pair density waves have now been widely detected in exotic superconductors. Understanding how these density waves emerge - and become suppressed by external parameters - is a key research direction in condensed matter physics. Here we study the temperature and magnetic-field evolution of charge density waves in the rare spin-triplet superconductor candidate UTe2 using scanning tunneling microscopy/spectroscopy. We reveal that charge modulations composed of three different wave vectors gradually weaken in a spatially inhomogeneous manner, while persisting to surprisingly high temperatures of 10-12 K. We also reveal an unexpected decoupling of the three-component charge density wave state. Our observations match closely to the temperature scale potentially related to short-range magnetic correlations, providing a possible connection between density waves observed by surface probes and intrinsic bulk features. Importantly, charge density wave modulations become suppressed with magnetic field both below and above superconducting Tc in a comparable manner. Our work points towards an intimate connection between hidden magnetic correlations and the origin of the unusual charge density waves in UTe2.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

RATIONALE: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. OBJECTIVES: We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). METHODS: We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. MEASUREMENTS AND MAIN RESULTS: Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups. CONCLUSIONS: Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03229499.

Fatally impaired glucose digestion by propylene glycol in Aedes aegypti (Diptera: Culicidae) and co-formulation with terpenoids for enhancing attractive toxic sugar baits.

Propylene glycol (PG) demonstrates greater efficacy than other sugar polyols. However, the attributes it confers for toxicity and possible co-formulation with other ingredients are unknown. To evaluate this, α-glucosidase and glucose oxidase reactions were performed in Aedes aegypti (L.) (Diptera: Culicidae) to categorize if PG behaves similarly to prior studied sugar alcohols. A combination of no-choice and choice assays was used to determine effective ratios of PG and sucrose, competitiveness against a control of 10% sucrose, and whether mosquitoes recovered from PG consumption. The final trials included ß-cyclodextrin encapsulated cinnamon leaf oil, clove stem oil, patchouli oil, garlic oil, cedarwood oil, and papaya seed oil formulated with 5% sucrose + 5% PG. PG functioned as a linear competitive inhibitor of α-glucosidase. The efficacy of PG was synergized by co-ingestion with equivalent ratios of sucrose. Unlike the high diuretic response to other sugar alcohols, PG resulted in diminished excretion regardless of being co-formulated with sucrose or terpenoids. PG is not especially competitive against unadulterated sugar meals but is likewise not clearly repellent. Although mosquitoes did not recover from ingestion of the glycol meals, there was no indication that mortality would continue to accumulate once the treatments were removed. Of the terpenoids tested, cinnamon and patchouli caused ~50% or less mortality; garlic, cedarwood, and clove caused 80-90% mortality; and papaya seed caused 100% mortality, exceeding all other test groups and the formulation blank. PG is a useful supporting ingredient in attractive toxic sugar bait formulations with flexibility in formulation.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction which can impact other solid organs. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied. OBJECTIVES: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2014. METHODS: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. MEASUREMENTS AND MAIN RESULTS: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on six-minute walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. CONCLUSIONS: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared to placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Skeletal muscle architecture and aging: A comparison of ultrasound techniques and an assessment of intrarater reliability.

OBJECTIVE: To assess intrarater reliability of ultrasound-determined measurements of skeletal muscle characteristics across different measurement outcomes, imaging techniques, and age groups. METHODS: 2D ultrasound images (B-mode) of the quadriceps were obtained from young (26 ± 4 year, n = 8 M, 8 F) and older (70 ± 7 year, n = 7 M, 5 F) adults on two occasions, separated by 6 ± 3 days. With participants in both standing and supine postures, images were collected from five anatomical sites along the anterior (two sites) and lateral (three sites) compartments of the thigh corresponding to 56%, 39%, and 22% (lateral only) of femur length. Images were analysed for muscle thickness, pennation angle, and echogenicity. Intraclass correlation coefficients (ICC) were used to assess reliability. RESULTS: Muscle thickness values were higher (p < 0.05) on images collected in the stand versus supine posture only for muscles of the anterior compartment, independent of age. Echogenicity values were higher (p < 0.05) in the vastus intermedius on images collected in the supine versus stand posture only in older adults. Pennation angle values were not impacted by imaging posture (p > 0.05). ICC values for thickness, echogenicity, and pennation angle were generally higher for analyses conducted on images collected in the supine versus stand posture. Imaging posture generated a greater difference in ICC values in the lateral versus anterior muscles and in older versus younger participants. CONCLUSION: Our findings suggest that participant posture during imaging impacts the absolute values and intrarater reliability of ultrasound-determined muscle characteristics in a muscle-specific fashion, and this effect is greater in older compared to younger individuals.