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The San Joaquin Valley (SJV) experiences some of the worst ozone air quality in the US, frequently exceeding the California 8 h standard of 70.4 ppb. To improve our understanding of trends in the number of ozone violations in the SJV, we analyze observed relationships between organic reactivity, nitrogen oxides (NOx), and daily maximum temperature in the southern SJV using measurements made as part of California at the Nexus of Air Quality and Climate Change in 2010 (CalNex-SJV). We find the daytime speciated organic reactivity with respect to OH during CalNex-SJV has a temperature-independent portion with molecules typically associated with motor vehicles being the major component. At high temperatures, characteristic of days with high ozone, the largest portion of the total organic reactivity increases exponentially with temperature and is dominated by small, oxygenated organics and molecules that are unidentified. We use this simple temperature classification to consider changes in organic emissions over the last and next decade. With the CalNex-SJV observations as constraints, we examine the sensitivity of ozone production (PO3) to future NOx and organic reactivity controls. We find that PO3 is NOx-limited at all temperatures on weekends and on weekdays when daily maximum temperatures are greater than 29 °C. As a consequence, NOx reductions are the most effective control option for reducing the frequency of future ozone violations in the southern SJV. © 2014 Author(s).

We examine spatial variations in the weekday-weekend pattern of NO 2 over the Los Angeles metropolitan area using the Ozone Monitoring Instrument (OMI) and then compare the observations to calculations using the WRF-Chem model. We find that the spatial pattern of the weekday-weekend variations of the NO2 column in the model is significantly different than observed. A sensitivity study shows that the contrasting spatial pattern of NO2 on weekdays and weekends is a useful diagnostic of emissions and chemistry. These improvements suggest that constraints from space-based observations of the processes affecting urban photochemistry (e.g., spatial patterns of emissions, ratios of VOC to NOx emissions, rate constants) are possible at a level of detail not previously described. © 2014 Author(s).

Background: Canine vector-borne diseases (VBDs) induce non-specific dysproteinemias, detectable by serum protein electrophoresis (SPE). VBDs have been reported to induce a monoclonal gammopathy pattern. Monoclonal gammopathies are commonly the result of paraprotein (M-protein) produced by an immunoglobulin-secreting neoplasm., Objectives: The aims of this study were to characterize and compare SPE and immunofixation (IF) changes, evaluate the performance of previously identified SPE and IF interpretative criteria, and identify M-proteins in a cohort of dogs seropositive for a VBD and with an unknown history for an immunoglobulin-secreting neoplasm., Methods: A total of 143 serum samples from dogs that tested seropositive for different vector-borne pathogens were assessed by SPE. Cases with abnormal globulin fractions were further characterized by IF. Protein fraction and IF labeling results were evaluated using Kruskal-Wallis with Dunn's multiple comparisons and principal component analysis (PCA)., Results: IF was performed in 112 VBD-seropositive samples with dysproteinemia evaluated by SPE. Most (84/112, 75%) had a polyclonal expansion. Only two dogs had findings suggestive of an M-protein when considering both SPE and immunofixation. PCA clustered E.canis/A.phagocytophilum and B.gibsoni/CM.haematoparvum groups with relatively more γ-globulins than albumin and α-globulins, and the B.gibsoni/CM.haematoparvum group with more prominent IgA and IgM labeling than IgG labeling. Additionally, D.immitis clustered with more prominent β-globulins than γ-globulins and more IgG4 than IgG-FC., Conclusions: The previously derived interpretative criteria suggested an M-protein in very few VBD-seropositive dogs. PCA identified SPE and immunofixation pattern differences between dogs seropositive for different infectious agents., (© 2024 The Author(s). Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0896.

Atrial fibrillation, the most prevalent cardiac arrhythmia, has witnessed significant advancements in treatment modalities, transitioning from invasive procedures like the maze procedure to minimally invasive catheter ablation techniques. This review focuses on recent improvements in anesthetic approaches that enhance outcomes in catheter atrial fibrillation ablation. We highlight the efficacy of contact force sensing catheters with steerable introducer sheaths, which outperform traditional catheters by ensuring more effective contact time and lesion formation. Comparing general anesthesia with conscious sedation, we find that general anesthesia provides superior catheter stability due to reduced respiratory variability, resulting in more effective lesion formation, and reduced pulmonary vein reconnection. The use of high-frequency jet ventilation under general anesthesia, delivering low tidal volumes, effectively minimizes left atrial movement, decreasing catheter displacement and procedure time, and reducing recurrence in paroxysmal atrial fibrillation. An alternative, high-frequency low tidal volume ventilation using conventional ventilators, also shows improved catheter stability and lesion durability compared to traditional ventilation methods. However, a detailed comparative study of high-frequency jet ventilation, high-frequency low tidal volume ventilation, and conventional mechanical ventilation in catheter ablation for atrial fibrillation is lacking. This review emphasizes the need for such studies to identify optimal anesthetic techniques, potentially enhancing patient outcomes in atrial fibrillation treatment. Our findings suggest that careful selection of anesthetic methods, including ventilation strategies, plays a crucial role in the success of catheter ablation for atrial fibrillation, warranting further research for evidence-based practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acute mountain sickness occurs due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but inhibits exercise performance. Methazolamide (MZ), an analogous drug, has similar prophylactic benefits but does not impair isolated muscle mass exercise performance in normoxia. We sought to compare whole-body exercise performance in acute hypoxia (F I O 2 = 0.15) between AZ, MZ and placebo (PLA). Fifteen healthy participants completed 5 testing visits: day 1 maximal exercise test, day 2 a familiarization, and days 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial performed after a 2-day dosing protocol of either AZ (250 mg t.i.d.), MZ (100 mg b.i.d.) or PLA (t.i.d.); the order was randomized and double-blinded. Prior to exercise, capillary blood samples were taken, and maximal voluntary contractions of quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest compared to PLA (capillary H + 47±3, 43±2, 39±2 nmol for AZ, MZ and PLA respectively, p<0.01). Time to complete 5-km with PLA (562±32 seconds, p<0.01) was significantly faster than AZ and MZ (577±38 vs. 581±37s respectively), with no differences between AZ and MZ (p=0.96). There were no differences in average ventilation (124±27, 127±24, 127±19 l/min) and oxyhemoglobin saturation (87±2, 88±2, 88±3%) between AZ, MZ and PLA respectively (p>0.05). Overall, both AZ and MZ impair whole-body exercise performance in acute normobaric hypoxia.

Objective: Research has demonstrated the effectiveness of interventions to reduce organizational skills deficits and homework problems, including the clinic-based Organizational Skills Training (OST-C) program (Abikoff et al., 2013). In this study, OST-C was adapted for schools as a small-group (Tier 2) intervention delivered by school partners (OST-T2)., Method: The study was conducted in 22 schools serving students from diverse backgrounds. Students (n = 186; 122 male) in Grades 3-5, ages 8-12 (M = 9.7 years; SD = 0.88) with organizational skills deficits referred by teachers were enrolled. Schools were randomly assigned to OST-T2 or treatment as usual with waitlist. OST-T2 consisted of sixteen 35-min child sessions, two caregivers, and two teacher consultations. Outcomes were evaluated with longitudinal mixed effects modeling at posttreatment, 5-month and 12-month follow-up using caregiver and teacher reports of organizational skills, homework, and academic performance., Results: OST-T2 resulted in reductions in organizational skills deficits on caregiver and teacher report (p < .001) at posttreatment and 5-month follow-up (effect sizes [ES], Cohen's d = 0.96, 1.20). Findings also revealed a reduction in caregiver-reported homework problems at posttreatment and 5-month follow-up (p < .001, ES = 0.60, 0.72), and an improvement in teacher-rated homework at posttreatment (p = .007, ES = 0.64). Effects were attenuated at 12-month follow-up. The effects of OST-T2 on academic measures were not significant., Conclusions: Findings provide evidence for the immediate and short-term effectiveness of OST-T2 delivered by school professionals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Multiple listing (ML) is a practice used to increase the potential for transplant but is controversial due to concerns that it disproportionately benefits patients with greater access to health care resources., Research Question: Is there disparity in ML practices based on social deprivation in the United States and does ML lead to quicker time to transplant?, Study Design and Methods: A retrospective cohort study of adult (≥ 18 years of age) lung transplant candidates listed for transplant (2005-2018) was conducted. Exclusion criteria included heart only or heart and lung transplant and patients relisted during the observation period. Data were obtained from the United Network for Organ Sharing Standard Transplant Analysis and Research File. The first exposure of interest was the Social Deprivation Index with a primary outcome of ML status, to assess disparities between ML and single listing (SL) participants. The second exposure of interest was ML status with a primary outcome of time to transplant, to assess whether implementation of ML leads to quicker time to transplant., Results: A total of 35,890 patients were included in the final analysis, of whom 791 (2.2%) were ML and 35,099 (97.8%) were SL. ML participants had lower median level of social deprivation (5 units, more often female: 60.0% vs 42.3%) and lower median lung allocation score (35.3 vs 37.3). ML patients were more likely to be transplanted than SL patients (OR, 1.42; 95% CI, 1.17-1.73), but there was a significantly quicker time to transplant only for those whom ML was early (within 6 months of initial listing) (subdistribution hazard ratio, 1.17; 95% CI, 1.04-1.32)., Interpretation: ML is an uncommon practice with disparities existing between ML and SL patients based on several factors including social deprivation. ML patients are more likely to be transplanted, but only if they have ML status early in their transplant candidacy. With changing allocation guidelines, it is yet to be seen how ML will change with the implementation of continuous distribution., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung transplantation lags behind other solid organ transplants in donor lung utilization due, in part, to uncertainty regarding donor quality. We sought to develop an easy-to-use donor risk metric that, unlike existing metrics, accounts for a rich set of donor factors. Our study population consisted of n = 26 549 adult lung transplant recipients abstracted from the United Network for Organ Sharing Standard Transplant Analysis and Research file. We used Cox regression to model graft failure (GF; earliest of death or retransplant) risk based on donor and transplant factors, adjusting for recipient factors. We then derived and validated a Lung Donor Risk Index (LDRI) and developed a pertinent online application (https://shiny.pmacs.upenn.edu/LDRI&#95;Calculator/). We found 12 donor/transplant factors that were independently predictive of GF: age, race, insulin-dependent diabetes, the difference between donor and recipient height, smoking, cocaine use, cytomegalovirus seropositivity, creatinine, human leukocyte antigen (HLA) mismatch, ischemia time, and donation after circulatory death. Validation showed the LDRI to have GF risk discrimination that was reasonable (C = 0.61) and higher than any of its predecessors. The LDRI is intended for use by transplant centers, organ procurement organizations, and regulatory agencies and to benefit patients in decision-making. Unlike its predecessors, the proposed LDRI could gain wide acceptance because of its granularity and similarity to the Kidney Donor Risk Index., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at approximately 1,535 m above sea level and compare these findings with healthy, nonsedated, brachycephalic dogs living at the same altitude., Animals: 120 adult nonbrachycephalic dogs and 20 adult brachycephalic dogs., Methods: Cases were prospectively enrolled from October 2021 to June 2022. Dogs were enrolled from the community or after presentation for wellness examinations or minor injuries including lacerations, nail injuries, and lameness. Physical examinations and systolic blood pressure (sBP) measurements were obtained before blood sample collection. Arterial blood was collected from the dorsal pedal artery or femoral artery. After data collection, brachycephalic dogs underwent pre- and postexercise tolerance assessments., Results: The mean and RI values for arterial pH (7.442; 7.375 to 7.515), partial pressure of oxygen in arterial blood (Pao2; 78.3; 59.2 to 92.7 mm Hg), partial pressure of carbon dioxide in arterial blood (Paco2; 28.0; 21.5 to 34.4 mm Hg), saturation of arterial oxygen (Sao2; 98.4; 84.3% to 101.4%), HCO3 (18.9; 14.9 to 22.4 mmol/L), concentration of total hemoglobin (ctHb; 17.5; 13.4 to 21.1 g/dL), and sBP (133; 94 to 180 mm Hg) were established for healthy nonbrachycephalic dogs at 1,535-m altitude. All aBG measurements were statistically and clinically different from those previously reported for dogs at sea level. Brachycephalic dogs had significantly lower Pao2 and Sao2 (P = .0150 and P = .0237, respectively) and significantly higher ctHb (P = .0396) compared to nonbrachycephalic dogs acclimatized to the same altitude; the nonbrachycephalic RIs were not transferable to the brachycephalic dogs for Pao2., Clinical Relevance: This study represents the first collation of aBG measurements for healthy nonbrachycephalic dogs acclimatized to an altitude of 1,535 m. Additionally, this study identified differences in arterial oxygenation measurements between brachycephalic and nonbrachycephalic dogs. RIs in brachycephalic dogs need to be established.

Current guidelines recommend using Bland-Altman plots (BA-plots), also called Difference plots, as part of method comparison evaluation in the veterinary clinical pathology laboratory. Analysis of differences can meaningfully augment linear regression techniques and allows fuller summarization of the performance of two methods relative to each other. This work summarizes the current literature on BA-plot composition and evaluation. Model data is used to demonstrate data evaluation approaches based on the observed differences, the combined inherent imprecision of the methods, and clinically relevant performance goals. Common limitations of the approaches, including points of frequent misinterpretation, are presented. BA-plot analysis can be part of an intentionally crafted method comparison study that provides analytically and clinically relevant data., (© 2023 The Author. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

This study examined 24-h hydration parameters among collegiate, male soccer players (n = 17) during twice (X2) and once (X1) per day practice schedules in the heat. Urine specific gravity (USG) and body mass were measured before morning practices, afternoon practice (X2)/team meeting (X1), and the next morning practices. Fluid intake, sweat losses, and urinary losses were assessed during each 24-h window. Pre-practice body mass or USG did not differ among the timepoints. Sweat losses differed among all practices (p < 0.05) and averaged approximately 2.181±0.693 (X2AM) 1.710±0.474 (X2PM), and 3.361±0.956 L (X1AM), but players averaged replacing >50% of sweat losses with fluid intake every practice. Fluid intake during and between practices from practice 1 to the afternoon practice for X2 resulted in a positive fluid balance for X2 (+0.446±0.916 L). However, higher sweat loss during the initial morning practice and lower relative fluid intake prior to the afternoon team meeting the following morning resulted in a negative fluid balance (-0.304±0.675 L; p < 0.05: Cohen's d = 0.94) over the same time period for X1. By the start of the next morning practice sessions, both X1 (+0.664±1.051 L) and X2 (+0.446±0.916 L) were in positive fluid balance, respectively. Ample fluid consumption opportunities, scaled down practice intensities during X2, and potentially intentional greater relative fluid intake during X2 training resulted in no difference in fluid shift versus an X1 schedule before the start of practices. The majority of players maintained fluid balance drinking ad libitum regardless of practice schedule., Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Inc.)

The ratio of κ light chains to λ light chains (κ:λ) in serum is used as a biomarker of immunoglobulin secreting neoplasia in humans but has not been evaluated in dogs. A mass-spectrometry based method for determining the canine serum κ:λ was developed and used to evaluate samples from control dogs, dogs with an infectious aetiology, dogs with secretory plasma cell tumours (sPCT) and dogs with non-secretory B cell neoplasia. A human-targeted immunoturbidometric κ:λ assay and immunofixation using antisera targeting human κ light chain or λ light chain was also performed on all samples. Using whole serum samples, the MS-based κ:λ method identified 5 sPCT as κ-predominant (mean κ:λ = 3.307) and 5 sPCT as λ-predominant (mean κ:λ = 0.023) and documented differences between these groups and all other groups (p < 0.05 for all). The infectious aetiology group had a lower mean κ:λ ratio (mean κ:λ = 0.069) than control samples (mean κ:λ = 0.103, p = 0.035). Similar results were obtained when samples were enriched for proteins between 10 and 50 kDa using size exclusion chromatography, except for the statistical difference between the control and infectious aetiology group. All λ-predominant cases had only anti-human λ light chain labelling by immunofixation. Three κ-predominant cases had only anti-human κ-light chain labelling and the remaining two cases did not label with either antisera by immunofixation. The immunoturbidometric method had high analytical CV% (λ light chain CV = 13%, κ light chain CV = 50%), was unable to measure light chains in 20.5% of samples and did not distinguish groups. The data suggests that the human-targeted immunoturbidometric method would not be diagnostically useful and that the MS-derived serum κ:λ may be a useful biomarker of canine immunoglobulin secretory neoplasia which may have the ability to distinguish neoplasia from infectious causes of immunoglobulin secretion., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes 1 . Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear 2,3 . Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake 4-7 . Here we find that, in addition to suppressing appetite, GDF15 counteracts compensatory reductions in energy expenditure, eliciting greater weight loss and reductions in non-alcoholic fatty liver disease (NAFLD) compared to caloric restriction alone. This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL-β-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice. These data indicate that therapeutic targeting of the GDF15-GFRAL pathway may be useful for maintaining energy expenditure in skeletal muscle during caloric restriction., (© 2023. The Author(s).)

Cardiomyopathy has become one of the leading causes of death in patients with Duchenne muscular dystrophy (DMD). We recently reported that the inhibition of the interaction between the receptor activator of nuclear factor κB ligand (RANKL) and receptor activator of nuclear factor κB (RANK) significantly improves muscle and bone functions in dystrophin-deficient mdx mice. RANKL and RANK are also expressed in cardiac muscle. Here, we investigate whether anti-RANKL treatment prevents cardiac hypertrophy and dysfunction in dystrophic mdx mice. Anti-RANKL treatment significantly reduced LV hypertrophy and heart mass, and maintained cardiac function in mdx mice. Anti-RANKL treatment also inhibited NFκB and PI3K, two mediators implicated in cardiac hypertrophy. Furthermore, anti-RANKL treatment increased SERCA activity and the expression of RyR, FKBP12, and SERCA2a, leading possibly to an improved Ca 2+ homeostasis in dystrophic hearts. Interestingly, preliminary post hoc analyses suggest that denosumab, a human anti-RANKL, reduced left ventricular hypertrophy in two patients with DMD. Taken together, our results indicate that anti-RANKL treatment prevents the worsening of cardiac hypertrophy in mdx mice and could potentially maintain cardiac function in teenage or adult patients with DMD.

Rationale: Low and high body mass index (BMI) are associated with increased mortality after lung transplantation. Why extremes of BMI might increase risk of death is unknown. Objectives: To estimate the association of extremes of BMI with causes of death after transplantation. Methods: We performed a retrospective study of the United Network for Organ Sharing database, including 26,721 adults who underwent lung transplantation in the United States between May 4, 2005, and December 2, 2020. We mapped 76 reported causes of death into 16 distinct groups. We estimated cause-specific hazards for death from each cause using Cox models. Results: Relative to a subject with a BMI of 24 kg/m 2 , a subject with a BMI of 16 kg/m 2 had 38% (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 0.99-1.90), 82% (HR, 1.82; 95% CI, 1.34-2.46), and 62% (HR, 1.62; 95% CI, 1.18-2.22) increased hazards of death from acute respiratory failure, chronic lung allograft dysfunction (CLAD), and infection, respectively, and a subject with a BMI of 36 kg/m 2 had 44% (HR, 1.44; 95% CI, 0.97-2.12), 42% (HR, 1.42; 95% CI, 0.93-2.15), and 185% (HR, 2.85; 95% CI, 1.28-6.33) increased hazards of death from acute respiratory failure, CLAD, and primary graft dysfunction, respectively. Conclusions: Low BMI is associated with increased risk of death from infection, acute respiratory failure, and CLAD after lung transplantation, whereas high BMI is associated with increased risk of death from primary graft dysfunction, acute respiratory failure, and CLAD.