Occurrence of "Natural Selection" in Successful Small Molecule Drug Discovery.

Published compounds from ChEMBL version 32 are used to seek evidence for the occurrence of "natural selection" in drug discovery. Three measures of natural product (NP) character were applied, to compare time- and target-matched compounds reaching the clinic (clinical compounds in phase 1-3 development and approved drugs) with background compounds (reference compounds). Pseudo-NPs (PNPs), containing NP fragments combined in ways inaccessible by nature, are increasing over time, reaching 67% of clinical compounds first disclosed since 2010. PNPs are 54% more likely to be found in post-2008 clinical versus reference compounds. The majority of target classes show increased clinical compound NP character versus their reference compounds. Only 176 NP fragments appear in >1000 clinical compounds published since 2008, yet these make up on average 63% of the clinical compound's core scaffolds. There is untapped potential awaiting exploitation, by applying nature's building blocks─"natural intelligence"─to drug design.

Duration of triple antithrombotic therapy and clinical outcomes after percutaneous coronary intervention in atrial fibrillation.

BACKGROUND: Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. RESEARCH DESIGN AND METHODS: A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. RESULTS: Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). CONCLUSIONS: TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.

Assessment of bronchodilator response in preschoolers: A systematic review.

BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.

Cardiovascular Responses to Occupational Physical Activity are Exaggerated by Work-Related Stress and Low Fitness.

OBJECTIVES: Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness. METHODS: OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (HR x BP, RPP) were measured objectively for 24-hours in nineteen male workers. Work-related stress was measured using the Stress-in-General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions. RESULTS: Associations between OPA and RPP, HR, and BP were stronger with high stress (p < 0.05). Associations of work-time MVPA and RPP were attenuated with higher fitness (p < 0.05). CONCLUSIONS: OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA.

Intraoperative fluid management is not predictive of AKI in major pancreatic surgery: a retrospective cohort study.

BACKGROUND: Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery. METHODS: This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018-December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes. RESULTS: AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8-35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4-16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality. CONCLUSION: In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.

Biochemical characterisation of a cassava (Manihot esculenta crantz) diversity panel for post-harvest physiological deterioration; metabolite involvement and environmental influence.

Cassava (Manihot esculenta Crantz) produces edible roots, a major carbohydrate source feeding more than 800 million people in Africa, Latin America, Oceania and Asia. Post-harvest physiological deterioration (PPD) renders harvested cassava roots unpalatable and unmarketable. Decades of research on PPD have elucidated several genetic, enzymatic and metabolic processes involved. Breeding populations were established to enable verification of robust biomarkers for PPD resistance. For comparison, these PPD populations have been cultivated concurrently with diversity population for carotenoid (ß-carotene) content. Results highlighted a significant variation of the chemotypes due to environmental factors. Less than 3% of the detected molecular features showed consistent trends between the two harvest years and were putatively identified as phenylpropanoid derived compounds (e.g. caffeoyl rutinoside). The data corroborated that ∼20 µg ß-carotene/g DW can reduced the PPD response of the cassava roots to a score of ∼1. Correlation analysis showed a significant correlation of ß-carotene content at harvest to PPD response (R2 -0.55). However, the decrease of ß-carotene over storage was not significantly correlated to initial content or PPD response. Volatile analysis observed changes of apocarotenoids derived from ß-carotene, lipid oxidation products (alkanes, alcohols and carbonyls and esters) and terpenes. The majority of these volatiles (>90%) showed no significant correlation to ß-carotene or PPD. Observed data indicated an increase (∼2-fold) of alkanes in varieties with ß-carotene >10 µg/g DW and a decrease (∼60%) in varieties with less ß-carotene. Fatty acid methyl esters with a chain length > C9 were detected solely after storage and show lower levels in varieties with higher ß-carotene content. In combination with correlation values to PPD (R2 ∼0.3; P-value >0.05), the data indicated a more efficient ROS quenching mechanism in PPD resistant varieties.

In-Home Health Risk Assessments And Chart Reviews Contribute To Coding Intensity In Medicare Advantage.

There is widespread agreement that taxpayers pay more when Medicare beneficiaries are enrolled in Medicare Advantage (MA) plans than if those beneficiaries were enrolled in traditional Medicare. MA plans are paid on the basis of submitted diagnoses and thus have a clear incentive to encourage providers to find and report as many diagnoses for their enrollees as possible. Two mechanisms that MA plans use to identify diagnoses that are not available for beneficiaries in traditional Medicare are in-home health risk assessments and chart reviews. Using MA encounter data for 2015-20, I isolated the impact of these two types of encounters on the risk scores used for payments to MA plans during 2016-21. I found that encounter-based risk scores for MA enrollees were higher by 0.091 points, or 7.4 percent, in 2021 when in-home health risk assessments and chart reviews were included than they would have been without the use of these tools.

Examining for gender differences in return to learn following sport-related concussion in high school student athletes.

OBJECTIVE: Prior studies have investigated associations between gender, symptom resolution, and time to return to play following sport-related concussion (SRC). However, there is a notable gap in research regarding the association between gender and return to learn (RTL) in adolescents. Therefore, this study 1) compared the patterns of RTL between boys and girls who are high school student athletes, and 2) evaluated the possible association between gender and time to RTL after adjusting for covariates. METHODS: A retrospective cohort study of a prospective surveillance program that monitored concussion recovery of athletes in high schools throughout the state of Maine between February 2015 and January 2023 was performed. The primary independent variable was gender, dichotomized as boys and girls. The primary outcome was time to RTL, defined by the number of days for an athlete to return to school without accommodations. Mann-Whitney U-tests were used to compare RTL between the boys and girls. Each athlete's RTL status was dichotomized (i.e., returned vs had not returned) at several time points following injury (i.e., 1, 2, 3, and 4 weeks), and chi-square tests were performed to compare the proportions who achieved RTL between groups. Multivariable linear regression analyses were performed to evaluate the predictive value of gender on RTL. Covariates included age, number of previous concussions, history of learning disability or attention-deficit disorder or attention-deficit/hyperactivity disorder, history of a psychological condition, history of headaches or migraines, initial Sport Concussion Assessment Tool (SCAT3/SCAT5) score, and days to evaluation. RESULTS: Of 895 high school athletes, 488 (54.5%) were boys and 407 (45.5%) were girls. There was no statistically significant difference in median [IQR] days to RTL between genders (6.0 [3.0-11.0] vs 6.0 [3.0-12.0] days; U = 84,365.00, p < 0.375). A greater proportion of boys successfully returned to learn without accommodations by 3 weeks following concussion (93.5% vs 89.4%; χ2 = 4.68, p = 0.030), but no differences were found at 1, 2, or 4 weeks. A multivariable model predicting days to RTL showed that gender was not a significant predictor of RTL (p > 0.05). Longer days to evaluation (ß = 0.10, p = 0.021) and higher initial SCAT3/SCAT5 scores (ß = 0.15, p < 0.001) predicted longer RTL. CONCLUSIONS: In a cohort of high school athletes, RTL did not differ between boys and girls following SRC. Gender was not a significant predictor of RTL. Longer days to evaluation and higher initial symptom scores were associated with longer RTL.

The Aromatic Scents of Four Plants in Learning and Memory of Drosophila melanogaster.

Introduction: Folkloric claims have surrounded essential oils, including their enhancement of learning and memory through inhalational exposure. Few studies in humans have shown a benefit in cognition, albeit incremental. However, this benefit may not be entirely attributable to the essential oil aroma but may be confounded by psychological associations. We investigated rosemary, peppermint, lemon, and coffee aromas in a learning and memory model of Drosophila melanogaster to eliminate this confounder. Methods: We screened for concentrations of the four treatments that are non-stimulatory for altered locomotory behavior in the flies. At these concentrations, we determined if they were chemoneutral (i.e., neither chemoattractant nor chemorepellent) to the flies. Learning and memory of the flies exposed to these aromas were determined using an Aversive Phototaxis Suppression (APS) assay. Results: The aromas of rosemary, peppermint, and lemon that did not elicit altered mobility in the flies were from dilute essential oil solutions that ranged from 0.2 to 0.5% v/v; whereas for the aroma in coffee, it was at a higher concentration of 7.5% m/v. At these concentrations, the aromas used were found to be chemoneutral towards the flies. We observed no improvement in both learning and memory in the four aromas tested. While a significant reduction (p < 0.05) in learning was observed when flies were treated with the aromas of rosemary, peppermint, and coffee, a significant reduction (p < 0.05) in memory was only observed in the peppermint aroma treatment. Conclusion: This study demonstrated that in the absence of psychological association, the four aromas do not enhance learning and memory.

Estimation of Acceptable Daily Intake Values based on Modeling and In Vivo Mutagenicity of NDSRIs of Fluoxetine, Duloxetine and Atomoxetine.

Nitrosamine drug substance related impurities or NDSRIs can be formed if an active pharmaceutical ingredient (API) has an intrinsic secondary amine that can undergo nitrosation. This is a concern as 1) nitrosamines are potentially highly potent carcinogens, 2) secondary amines in API are common, and 3) NDSRIs that might form from such secondary amines will be of unknown carcinogenic potency. Approaches for evaluating NDSRIs include read across, quantum mechanical modeling of reactivity, in vitro mutation data, and transgenic in vivo mutation data. These approaches were used here to assess NDSRIs that could potentially form from the drugs fluoxetine, duloxetine and atomoxetine. Based on a read across informed by modeling of physicochemical properties and mechanistic activation from quantum mechanical modeling, NDSRIs of fluoxetine, duloxetine, and atomoxetine were 10-100-fold less potent compared with highly potent nitrosamines such as NDMA or NDEA. While the NDSRIs were all confirmed to be mutagenic in vitro (Ames assay) and in vivo (TGR) studies, the latter data indicated that the potency of the mutation response was > 4400 ng/day for all compounds- an order of magnitude higher than published regulatory limits for these NDSRIs. The approaches described herein can be used qualitatively to better categorize NDSRIs with respect to potency and inform whether they are in the ICH M7R2-designated Cohort of Concern.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Developing transcriptomic signatures as a biomarker of cellular senescence.

Cellular senescence is a cell fate driven by different types of stress, where damaged cells exit from the cell cycle and, in many cases, develop an inflammatory senescence-associated secretory phenotype (SASP). Senescence has often been linked to driving aging and the onset of multiple diseases conferred by the harmful SASP, which disrupts tissue homeostasis and impairs the regular function of many tissues. This phenomenon was first observed in vitro when fibroblasts halted replication after approximately 50 population doublings. In addition to replication-induced senescence, factors such as DNA damage and oncogene activation can induce cellular senescence both in culture and in vivo. Despite their contribution to aging and disease, identifying senescent cells in vivo has been challenging due to their heterogeneity. Although senescent cells can express the cell cycle inhibitors p16Ink4a and/or p21Cip1 and exhibit SA-ß-gal activity and evidence of a DNA damage response, there is no universal biomarker for these cells, regardless of inducer or cell type. Recent studies have analyzed the transcriptomic characteristics of these cells, leading to the identification of signature gene sets like CellAge, SeneQuest, and SenMayo. Advancements in single-cell and spatial RNA sequencing now allow for analyzing senescent cell heterogeneity within the same tissue and the development of machine learning algorithms, e.g., SenPred, SenSig, and SenCID, to discover cellular senescence using RNA sequencing data. Such insights not only deepen our understanding of the genetic pathways driving cellular senescence, but also promote the development of its quantifiable biomarkers. This review summarizes the current knowledge of transcriptomic signatures of cellular senescence and their potential as in vivo biomarkers.

Benzene-1,2,4,5-tetrol.

The crystal structure of the title compound was determined at 120 K. It crystallizes in the triclinic space group P with four independent mol-ecules in the asymmetric unit. In the crystal, each symmetry-unique mol-ecule forms π-π stacks on itself, giving four unique π-π stacking inter-actions. Inter-molecular hydrogen bonding is observed between each pair of independent mol-ecules, where each hy-droxy group can act as a hydrogen-bond donor and acceptor.

Genomic determinants, architecture, and constraints in drought-related traits in Corymbia calophylla.

BACKGROUND: Drought adaptation is critical to many tree species persisting under climate change, however our knowledge of the genetic basis for trees to adapt to drought is limited. This knowledge gap impedes our fundamental understanding of drought response and application to forest production and conservation. To improve our understanding of the genomic determinants, architecture, and trait constraints, we assembled a reference genome and detected ~ 6.5 M variants in 432 phenotyped individuals for the foundational tree Corymbia calophylla. RESULTS: We found 273 genomic variants determining traits with moderate heritability (h2SNP = 0.26-0.64). Significant variants were predominantly in gene regulatory elements distributed among several haplotype blocks across all chromosomes. Furthermore, traits were constrained by frequent epistatic and pleiotropic interactions. CONCLUSIONS: Our results on the genetic basis for drought traits in Corymbia calophylla have several implications for the ability to adapt to climate change: (1) drought related traits are controlled by complex genomic architectures with large haplotypes, epistatic, and pleiotropic interactions; (2) the most significant variants determining drought related traits occurred in regulatory regions; and (3) models incorporating epistatic interactions increase trait predictions. Our findings indicate that despite moderate heritability drought traits are likely constrained by complex genomic architecture potentially limiting trees response to climate change.

The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wildtype and -mutant lower grade gliomas.

BACKGROUND: IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear. METHODS: We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling. RESULTS: We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion. CONCLUSIONS: Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.

Administration of 4% tetrasodium EDTA lock solution and central venous catheter complications in high-risk pediatric patients with intestinal failure: A retrospective cohort study.

BACKGROUND: Selection of central venous catheter (CVC) lock solution impacts catheter mechanical complications and central line-associated bloodstream infections (CLABSIs) in pediatric patients with intestinal failure. Disadvantages of the current clinical standards, heparin and ethanol lock therapy (ELT), led to the discovery of new lock solutions. High-risk pediatric patients with intestinal failure who lost access to ELT during a recent shortage were offered enrollment in a compassionate use trial with 4% tetrasodium EDTA (T-EDTA), a lock solution with antimicrobial, antibiofilm, and antithrombotic properties. METHODS: We performed a descriptive cohort study including 14 high-risk pediatric patients with intestinal failure receiving 4% T-EDTA as a daily catheter lock solution. CVC complications were documented (repairs, occlusions, replacements, and CLABSIs). Complication rates on 4% T-EDTA were compared with baseline rates, during which patients were receiving either heparin or ELT (designated as heparin/ELT). RESULTS: Patients initiated 4% T-EDTA at the time they were enrolled in the compassionate use protocol. Use of 4% T-EDTA resulted in a 50% reduction in CVC complications, compared with baseline rates on heparin/ELT (incidence rate ratio: 0.50; 95% CI, 0.25-1.004; P = 0.051). CONCLUSION: In a compassionate use protocol for high-risk pediatric patients with intestinal failure, the use of 4% T-EDTA reduced composite catheter complications, including those leading to emergency department visits, hospital admissions, additional procedures, and mortality. This outcome suggests 4% T-EDTA has benefits over currently available lock solutions.

Ammonium halide selective ion pair recognition and extraction with a chalcogen bonding heteroditopic receptor.

The first example of a heteroditopic receptor capable of cooperative recognition and extraction of ammonium salt (NH4X) ion-pairs is described. Consisting of a bidentate 3,5-bis-tellurotriazole chalcogen bond donor binding cleft, the appendage of benzo-15-crown-5 (B15C5) substituents to the tellurium centres facilitates binding of the ammonium cation via a co-facial bis-B15C5 sandwich complex, which serves to switch on chalcogen bonding-mediated anion binding potency. Extensive quantitative ion-pair recognition 1H NMR titration studies in CD3CN/CDCl3 (1 : 1, v/v) solvent media reveal impressive ion-pair binding affinities towards a variety of ammonium halide, nitrate and thiocyanate salts, with the heteroditopic receptor displaying notable ammonium halide salt selectivity. The prodigious solution phase NH4X recognition also translates to efficient solid-liquid and liquid-liquid extraction capabilities.

Distinguishing Mechanisms for Reactive Uptake at Liquid Surfaces via Angular Distributions of Inelastically Scattered Molecules.

Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated) have been measured. A pulsed, rotationally cold molecular beam (Ei = 35 kJ mol-1) of OH was scattered from refreshed liquid surfaces in a vacuum. Spatially and temporally resolved OH number densities were measured by pulsed, planar laser-induced fluorescence. Results are compared with those for the inert liquid perfluoropolyether. The clearly asymmetric distributions for 45° incidence add to the weight of evidence for predominantly impulsive scattering from all three liquids. However, we propose that significant differences in their shapes may be diagnostic of contrasting reaction mechanisms. Direct, near-specular trajectories survive preferentially on squalene, consistent with an addition mechanism removing those at more backward angles. This trend is reversed for squalane, as expected for direct abstraction. The results reinforce the need to consider the effects of composition-dependent contributions from different reaction mechanisms in the modeling of OH-aging of atmospheric aerosol particles.

Deep learning model utilizing clinical data alone outperforms image-based model for hernia recurrence following abdominal wall reconstruction with long-term follow up.

BACKGROUND: Deep learning models (DLMs) using preoperative computed tomography (CT) imaging have shown promise in predicting outcomes following abdominal wall reconstruction (AWR), including component separation, wound complications, and pulmonary failure. This study aimed to apply these methods in predicting hernia recurrence and to evaluate if incorporating additional clinical data would improve the DLM's predictive ability. METHODS: Patients were identified from a prospectively maintained single-institution database. Those who underwent AWR with available preoperative CTs were included, and those with < 18 months of follow up were excluded. Patients were separated into a training (80%) set and a testing (20%) set. A DLM was trained on the images only, and another DLM was trained on demographics only: age, sex, BMI, diabetes, and history of tobacco use. A mixed-value DLM incorporated data from both. The DLMs were evaluated by the area under the curve (AUC) in predicting recurrence. RESULTS: The models evaluated data from 190 AWR patients with a 14.7% recurrence rate after an average follow up of more than 7 years (mean ± SD: 86 ± 39 months; median [Q1, Q3]: 85.4 [56.1, 113.1]). Patients had a mean age of 57.5 ± 12.3 years and were majority (65.8%) female with a BMI of 34.2 ± 7.9 kg/m2. There were 28.9% with diabetes and 16.8% with a history of tobacco use. The AUCs for the imaging DLM, clinical DLM, and combined DLM were 0.500, 0.667, and 0.604, respectively. CONCLUSIONS: The clinical-only DLM outperformed both the image-only DLM and the mixed-value DLM in predicting recurrence. While all three models were poorly predictive of recurrence, the clinical-only DLM was the most predictive. These findings may indicate that imaging characteristics are not as useful for predicting recurrence as they have been for other AWR outcomes. Further research should focus on understanding the imaging characteristics that are identified by these DLMs and expanding the demographic information incorporated in the clinical-only DLM to further enhance the predictive ability of this model.

Measuring Access to Mental Health Services Among Primary Care Patients.

BACKGROUND: The lifetime risk of mental health disorders is almost 50% and, in any year, about 25% of the population have a psychiatric disorder. Many of those people are cared for in primary care settings. RESEARCH OBJECTIVE: Measure access to mental health services, such as getting counselling or prescription mental health medications, using new patient survey questions that can be added to Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. STUDY DESIGN: Surveys were conducted with a stratified probability sample of patients receiving primary care services in a single state in 2018-2019. Medicaid and privately insured patients were surveyed by mail or telephone, respectively. RESULTS: Approximately 14% of sampled patients responded to a survey. More than 10% of privately insured respondents and about 20% of Medicaid respondents got or tried to get appointments for mental health care. About 15% of privately insured respondents and 11% of Medicaid respondents reported problems getting appointments with counselors. Only 8%-9% of respondents seeking mental health medicines reported problems getting appointments for prescriptions. A composite measure combining access to counselors and prescribers of mental health medicines evidenced adequate internal consistency reliability. Group level reliability estimates were low. CONCLUSIONS: Many respondents got or tried to get mental health services and a substantial number reported problems getting appointments or getting mental health prescriptions. The tested questions can be combined into an Access to Mental Health Care measure, which can be included in patient experience surveys for ambulatory care to monitor access to behavioral health care.