Techniques in Management of Cholesteatoma: Subtotal Petrosectomy; Blind Sac Closure.

Subtotal petrosectomy plays a critical role in the management of late-stage cholesteatoma. This procedure is indicated either for recurrent cholesteatoma that has failed prior surgical therapies or when life-threatening infectious complications are present. By exenterating all diseased areas of the temporal bone and closing off the ear canal, subtotal petrosectomy has a much greater chance of removing cholesteatoma and preventing recidivism.

Fiddler crabs (Afruca tangeri) detect second-order motion in both intensity and polarization.

Motion vision is vital for a wide range of animal behaviors. Fiddler crabs, for example, rely heavily on motion to detect the movement of avian predators. They are known to detect first-order motion using both intensity (defined by spatiotemporal correlations in luminance) and polarization information (defined separately as spatiotemporal correlations in the degree and/or angle of polarization). However, little is known about their ability to detect second-order motion, another important form of motion information; defined separately by spatiotemporal correlations in higher-order image properties. In this work we used behavioral experiments to test how fiddler crabs (Afruca tangeri) responded to both second-order intensity and polarization stimuli. Fiddler crabs responded to a number of different intensity based second-order stimuli. Furthermore, the crabs also responded to second-order polarization stimuli, a behaviorally relevant stimulus applicable to an unpolarized flying bird when viewed against a polarized sky. The detection of second-order motion in polarization is, to the best of our knowledge, the first demonstration of this ability in any animal. This discovery therefore opens a new dimension in our understanding of how animals use polarization vision for target detection and the broader importance of second-order motion detection for animal behavior.

Hierarchical deep compartment modeling: A workflow to leverage machine learning and Bayesian inference for hierarchical pharmacometric modeling.

Population pharmacokinetic (PK) modeling serves as the cornerstone for understanding drug behavior within a specific population. It integrates subject covariates to elucidate the variability in PK parameters, thus enhancing predictive accuracy. However, covariate modeling within this framework can be intricate and time-consuming due to the often obscure structural relationship between covariates and PK parameters. Previous attempts, such as deep compartment modeling (DCM), aimed to streamline this process using machine learning techniques. Nonetheless, DCM fell short in assessing residual errors and interindividual variability (IIV), potentially leading to model misspecification and overfitting. Furthermore, DCM lacked the ability to quantify model uncertainty. To address these limitations, we introduce hierarchical deep compartment modeling (HDCM) as an advancement of DCM. HDCM harnesses machine learning to discern the interplay between covariates and PK parameters while simultaneously evaluating diverse levels of random effects and quantifying uncertainty through Bayesian inference. This tutorial provides a comprehensive application of the HDCM workflow using open-source Julia tools.

Emulating the Delivery of Sawtooth Proton Arc Therapy Plans on a Cyclotron-Based Proton Beam Therapy System.

Purpose: To evaluate and compare the deliverability of 'sawtooth' proton arc therapy (PAT) plans relative to static intensity modulated proton therapy (IMPT) at a cyclotron-based clinical facility. Methods: The delivery of single and dual arc Sawtooth PAT plans for an abdominal CT phantom and multiple clinical cases of brain, head and neck (H&N) and base of skull (BoS) targets was emulated under the step-and-shoot and continuous PAT delivery regimes and compared to that of a corresponding static IMPT plan. Results: Continuous PAT delivery increased the time associated with beam delivery and gantry movement in single/dual PAT plans by 4.86/7.34 min (brain), 7.51/12.40 min (BoS) and 6.59/10.57 min (H&N) on average relative to static IMPT. Step-and-shoot PAT increased this delivery time further by 4.79 min on average as the delivery was limited by gantry motion. Conclusions: The emulator can approximately model clinical sawtooth PAT delivery but requires experimental validation. No clear benefit was observed regarding beam-on time for sawtooth PAT relative to static IMPT.

Aerobic exercise training-induced bone and vascular adaptations in mice lacking adiponectin.

Adiponectin regulates lipid and glucose metabolism, and insulin sensitivity in various target organs; however, the effects of adiponectin on bone health remain controversial. Exercise training can enhance bone density, bone microarchitecture, and blood flow. This study aimed to elucidate the role of adiponectin in adaptations of bone microarchitecture and bone vasculature in response to aerobic exercise training. Adult male C57BL/6 wild-type (WT) and homozygous adiponectin knockout (AdipoKO) mice were either treadmill exercise trained or remained sedentary for 8-10 weeks. The trabecular structures of the distal femoral metaphysis, a weight-bearing bone, and the mandible, a non-weight-bearing bone, were examined using microcomputed tomography. The femoral principal nutrient arteries were isolated to assess vasoreactivity (vasodilation and vasoconstriction) and structural remodeling. At the femoral metaphysis, impaired trabecular bone structures, including reduced connectivity density and increased trabecular spacing, were observed in AdipoKO mice compared to WT mice. In addition, nitric oxide-mediated, endothelium-dependent vasodilation was substantially reduced, and wall-to-lumen ratio was significantly increased in the femoral principal nutrient artery of AdipoKO mice. Interestingly, although exercise training-induced enhancements in trabecular connectivity density were observed at the femoral metaphysis of both WT and AdipoKO, increased vasoconstrictor responses were only observed in the femoral principal nutrient artery of WT mice, not in the AdipoKO mice. In mandibular trabecular bone, exercise training increased trabecular bone volume fraction (BV/TV, %) and intersection surface in the mandible of both WT and AdipoKO mice. These findings indicate that adiponectin is crucial for maintaining normal bone microarchitecture and vasculature. Although the absence of adiponectin compromises bone vascular adaptation to exercise training in mice, some exercise training-induced alterations in bone microarchitecture occurred in the absence of adiponectin, suggesting contribution of compensatory mechanisms during exercise training.

Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial.

OBJECTIVE: To determine whether the relationship between average glucose (AG) levels and hemoglobin A1c (HbA1c) differs across racial/ethnic groups. RESEARCH DESIGN AND METHODS: We performed a prospective substudy of GRADE, a comparative effectiveness randomized trial conducted in 36 centers in the U.S. A total of 1,454 of the 5,047 participants in the GRADE cohort, including 534 non-Hispanic White (NHW), 389 non-Hispanic Black (NHB), and 327 Hispanic White patients and 204 patients of other racial/ethnic backgrounds, were included in the substudy. Continuous glucose monitoring (CGM) performed for 10 days was used to calculate AG10. Immediately after CGM, HbA1c and glycated albumin were measured. Fasting plasma glucose (FPG) and glucose area under the curve (AUC) were derived from a 75-g oral glucose tolerance test. RESULTS: The relationship between AG10 and HbA1c was significantly different for NHB compared with NHW patients and those of other racial/ethnic groups. HbA1c levels were 0.2-0.6 percentage points higher in NHB than in NHW patients for AG10 levels from 100 to 250 mg/dL. For an HbA1c of 7%, AG10 was 11 mg/dL higher for NHW than for NHB patients. Similar findings were observed across races for relationships of FPG and AUC with HbA1c and for glucose measurements with glycated albumin levels. Differences in the relationship between AG10 and HbA1c across racial groups remained after adjustments for any demographic or other differences between racial/ethnic subgroups. CONCLUSIONS: The relationship between several measures of glucose with HbA1c and glycated albumin consistently differed across races. These findings should be considered in setting treatment goals and diagnostic levels.

Genomic Diversity Illuminates the Environmental Adaptation of Drosophila suzukii.

Biological invasions carry substantial practical and scientific importance and represent natural evolutionary experiments on contemporary timescales. Here, we investigated genomic diversity and environmental adaptation of the crop pest Drosophila suzukii using whole-genome sequencing data and environmental metadata for 29 population samples from its native and invasive range. Through a multifaceted analysis of this population genomic data, we increase our understanding of the D. suzukii genome, its diversity and its evolution, and we identify an appropriate genotype-environment association pipeline for our dataset. Using this approach, we detect genetic signals of local adaptation associated with nine distinct environmental factors related to altitude, wind speed, precipitation, temperature, and human land use. We uncover unique functional signatures for each environmental variable, such as the prevalence of cuticular genes associated with annual precipitation. We also infer biological commonalities in the adaptation to diverse selective pressures, particularly in terms of the apparent contribution of nervous system evolution to enriched processes (ranging from neuron development to circadian behavior) and to top genes associated with all nine environmental variables. Our findings therefore depict a finer-scale adaptive landscape underlying the rapid invasion success of this agronomically important species.

Development of a General Composite Scale (GENCOMS) for Progressive Neurodegenerative Diseases and Implications for the Assessment of Disease-Modifying Therapies.

INTRODUCTION: The reliable assessment of treatment outcomes for disease-modifying therapies (DMT) in neurodegenerative disease is challenging. The objective of this paper is to describe a generalized framework for developing composite scales that can be applied in diverse, degenerative conditions, termed "GENCOMS." Composite scales optimize the sensitivity for detecting clinically meaningful effects that slow disease progression. METHODS: The GENCOMS method relies on robust natural history data and/or placebo arm data from DMT trials. Validated scales that are core to the disease process have been identified, and item level data obtained to standardize the response outcomes from 0 (best possible score) to 1 (worst possible score). A partial least squares regression analysis was conducted with temporal change as the dependent variable and change scores in standardized items as the explanatory variables. The derived model coefficients constitute a weighted sum of items that most effectively measure disease progression. RESULTS: The resultant composite scale was optimized to detect disease progression and can be examined in a range of slow or fast progressing populations. The scale can be used in studies with comparable patient populations as an endpoint optimized to measure disease progression and therefore ideally suited to assess treatment effects in DMTs. CONCLUSION: The methodology presented here provides a generalizable framework for developing composite scales in the assessment of neurodegenerative disease progression and evaluation of DMT effects. By objectively selecting and weighting items from previously validated measures based solely on their sensitivity to disease progression, this methodology allows for the creation of a more responsive measurement of clinical decline. This heightened sensitivity to clinical decline can be utilized to detect modest yet meaningful treatment effects in the early stages of neurogenerative diseases, when it is optimal to begin a DMT.

The test-retest reliability and validity of food photography and food diary analyses.

AIMS: To assess test-retest reliability of both food photography and food diary methods and validity of these data against known values derived from food labels. METHODS: Test-retest reliability analyses of food diary and food photography were compared using single foodstuffs using intra-class correlation coefficients, coefficients of variation, and limits of agreement. For food diaries, 24-h test-retest reliability was also examined. Validity was assessed against weighed analyses. As part of habitual intake, a single foodstuff (randomly allocated from 14 common foods) was consumed by 26 participants over 24-h. On two occasions (14 days apart), single-blind dietary analyses allowed estimation of foodstuff-specific energy and macronutrient content and 24-h intakes. RESULTS: For food diaries, test-retest reliability was acceptable (weight, energy, carbohydrate, protein, and fat: all intra-class correlation coefficients: >0.990, coefficient of variation percentage: <0.1%, limits of agreements: <0.1 to <0.1, p > 0.05, and effect size: <0.01). For food photography, test-retest reliability was acceptable for weight, energy, carbohydrate, and protein (all intra-class correlation coefficients: >0.898, coefficient of variation percentage: 3.6%-6.2%, limits of agreements: 1.1 to - 44.9, and effect size: 0.01-0.12). Food photography validity was worse than food diaries for all variables (percentage difference: 8.8%-15.3%, coefficient of variation percentage: 7.5%-13.8%, all p ≤ 0.05, and effect size: 0.001-0.11). CONCLUSIONS: Greater reliability and validity occurred in food diaries versus food photography. These findings suggest that using food photography may lead to an underestimation of energy and macronutrient content, which may have implications for dietary interventions and nutritional strategies.

Predicting recurrence of instability after a primary traumatic anterior shoulder dislocation.

Aims: The risk factors for recurrent instability (RI) following a primary traumatic anterior shoulder dislocation (PTASD) remain unclear. In this study, we aimed to determine the rate of RI in a large cohort of patients managed nonoperatively after PTASD and to develop a clinical prediction model. Methods: A total of 1,293 patients with PTASD managed nonoperatively were identified from a trauma database (mean age 23.3 years (15 to 35); 14.3% female). We assessed the prevalence of RI, and used multivariate regression modelling to evaluate which demographic- and injury-related factors were independently predictive for its occurrence. Results: The overall rate of RI at a mean follow-up of 34.4 months (SD 47.0) was 62.8% (n = 812), with 81.0% (n = 658) experiencing their first recurrence within two years of PTASD. The median time for recurrence was 9.8 months (IQR 3.9 to 19.4). Independent predictors increasing risk of RI included male sex (p < 0.001), younger age at PTASD (p < 0.001), participation in contact sport (p < 0.001), and the presence of a bony Bankart (BB) lesion (p = 0.028). Greater tuberosity fracture (GTF) was protective (p < 0.001). However, the discriminative ability of the resulting predictive model for two-year risk of RI was poor (area under the curve (AUC) 0.672). A subset analysis excluding identifiable radiological predictors of BB and GTF worsened the predictive ability (AUC 0.646). Conclusion: This study clarifies the prevalence and risk factors for RI following PTASD in a large, unselected patient cohort. Although these data permitted the development of a predictive tool for RI, its discriminative ability was poor. Predicting RI remains challenging, and as-yet-undetermined risk factors may be important in determining the risk.

Evaluation of a Novel Emergency General Surgery Handover: A Prospective Feasibility Study.

INTRODUCTION: High-quality health information handovers are critical to optimal patient care and trainee education. The purposes of this study were to assess the feasibility of implementing an emergency general surgery (EGS) morning handover and to explore its impact upon markers of clinical care. METHODS: This prospective feasibility study was conducted at a single academic tertiary-care medical center following implementation of a novel EGS morning handover process. We assessed organizational perspective through a two-part anonymous survey delivered to the EGS service staff (n = 29) and collected feasibility metrics daily at the morning handover meetings. Exploratory clinical metrics of quality improvement were compared between parallel 5-month periods preimplementation and postimplementation of the handover. Data were compared by descriptive statistics. RESULTS: One hundred and seventeen patients from March 1, 2022, to July 31, 2022, and 185 patients from March 1, 2023, to July 31, 2023, were identified prehandover and posthandover implementation, respectively, with an increase in time to operating room posting by 49% (95% confidence interval [CI]: 1.03-2.14) and no statistically significant change in length of stay. The average duration of the formalized EGS morning handover was 14 min (95% CI: 12:18-15:42) having an average of 12 questions asked (95% CI: 9.98-14.02) and an average attendance of 70% from essential personnel. Eighty-four percent of postimplementation survey responses indicated positive regard toward the new EGS handover. CONCLUSIONS: The implementation of an EGS morning handover is feasible, necessitating further studies to define the impact of the EGS morning handover upon clinical outcomes.

Selective deletion of Tsc1 from mouse cerebellar Purkinje neurons drives sex-specific behavioral impairments linked to autism.

There is a striking sex bias in the prevalence and severity of autism spectrum disorder (ASD) with 80% of diagnoses occurring in males. Because the molecular etiology of ASD is likely combinatorial, including interactions across multiple genetic and environmental factors, it is difficult to investigate the physiological mechanisms driving sex-specific differences. Loss of function mutations in TSC1 result in dysregulated mTORC1 signaling and underlie a multi-system disorder known as tuberous sclerosis (TSC). Interestingly, more than 50% of individuals diagnosed with TSC are also diagnosed with ASD, making TSC mutations one of the most prevalent monogenic causes of ASD. Mice harboring targeted deletion of Tsc1 selectively in cerebellar Purkinje neurons, referred to here as Tsc1 mut/mut , have multiple ASD-linked behavioral impairments, including deficits in social interactions, motor coordination, and vocalizations. However, these ASD-linked behavioral deficits have only been investigated using male Tsc1 mut/mut animals. Here, we used cohorts of male and female Tsc1 mut/mut animals to determine if behavioral impairments, previously identified in this model, are similar across sex. Specifically, we measured balance and motor coordination and social interaction behaviors in two age groups across sex. W e determined balance and motor coordination deficits are similar in male and female Tsc1 mut/mut mice, and that deficits in the firing of Tsc1 mut/mut Purkinje neurons located in the cerebellar vermis are also similar across sex. However, impairments in social approach behavior were found to be significantly more severe in Tsc1 mut/mut males compared to females. These results indicate the selective deletion of Tsc1 in Purkinje neurons differentially impairs cerebellar circuits based on sex.

Minimally Invasive Vacuum-Aided Extraction Technique for the Lipid Analysis of Historic Parchment.

Parchment is an ancient writing support formed from dehaired animal skins. Its manufacture comprises a series of liming and scraping steps before being stretched and dried under tension. Historical parchment represents a valuable source of cultural heritage which, until now, has limited investigations to noninvasive analyses to infer ink composition, degradation, or physical changes over time. We highlight the prospect of the molecular and isotope compositions of animal lipids from parchment as an untapped record of its production and the animal's diet and environment. We report a minimally invasive, total lipid extraction aided by a vacuum for historical parchments. The quantitative and qualitative compositions of lipid extracts obtained using this method are compared with those obtained using invasive sampling for nine sacrificial membranes dated 1765-1825 CE. This extraction method is then applied to membranes from the Chancery Parliament Rolls (1814-1820 CE) held by The National Archives, UK to obtain lipids and derive taxonomic and dietary information using their stable carbon isotope compositions. This novel vacuum-aided extraction allows, for the first time, animal lipids to be obtained from parchment minimally invasively, paving the way for dietary and paleoclimate studies using this well-dated and common material.

QCL Infrared Spectroscopy Combined with Machine Learning as a Useful Tool for Classifying Acetaminophen Tablets by Brand.

The development of new methods of identification of active pharmaceutical ingredients (API) is a subject of paramount importance for research centers, the pharmaceutical industry, and law enforcement agencies. Here, a system for identifying and classifying pharmaceutical tablets containing acetaminophen (AAP) by brand has been developed. In total, 15 tablets of 11 brands for a total of 165 samples were analyzed. Mid-infrared vibrational spectroscopy with multivariate analysis was employed. Quantum cascade lasers (QCLs) were used as mid-infrared sources. IR spectra in the spectral range 980-1600 cm-1 were recorded. Five different classification methods were used. First, a spectral search through correlation indices. Second, machine learning algorithms such as principal component analysis (PCA), support vector classification (SVC), decision tree classifier (DTC), and artificial neural network (ANN) were employed to classify tablets by brands. SNV and first derivative were used as preprocessing to improve the spectral information. Precision, recall, specificity, F1-score, and accuracy were used as criteria to evaluate the best SVC, DEE, and ANN classification models obtained. The IR spectra of the tablets show characteristic vibrational signals of AAP and other APIs present. Spectral classification by spectral search and PCA showed limitations in differentiating between brands, particularly for tablets containing AAP as the only API. Machine learning models, specifically SVC, achieved high accuracy in classifying AAP tablets according to their brand, even for brands containing only AAP.

Correction: Hyporheic hydraulic geometry: Conceptualizing relationships among hyporheic exchange, storage, and water age.

[This corrects the article DOI: 10.1371/journal.pone.0262080.].

Coordination structure and intermolecular interactions in copper(II) acetate complexes with 1,10-phenanthroline and 2,2'-bipyridine.

The crystal structures of two coordination compounds, (acetato-κO)(2,2'-bipyridine-κ2N,N')(1,10-phenanthroline-κ2N,N')copper(II) acetate hexahydrate, [Cu(C2H3O2)(C10H8N2)(C12H8N2)](C2H3O2)·6H2O or [Cu(bipy)(phen)Ac]Ac·6H2O, and (acetato-κO)bis(2,2'-bipyridine-κ2N,N')copper(II) acetate-acetic acid-water (1/1/3), [Cu(C2H3O2)(C10H8N2)2](C2H3O2)·C2H4O2·3H2O or [Cu(bipy)2Ac]Ac·HAc·3H2O, are reported and compared with the previously published structure of [Cu(phen)2Ac]Ac·7H2O (phen is 1,10-phenanthroline, bipy for 2,2'-bipyridine, ac is acetate and Hac is acetic acid). The geometry around the metal centre is pentacoordinated, but highly distorted in all three cases. The coordination number and the geometric distortion are both discussed in detail, and all complexes belong to the space group P-1. The analysis of the geometric parameters and the Hirshfeld surface properties dnorm and curvedness provide information about the metal-ligand interactions in these complexes and allow comparison with similar systems.

A Scoping Review of Animal Models for Development of Abdominal Adhesion Prevention Strategies.

INTRODUCTION: Abdominal adhesions represent a chronic postsurgical disease without reliable prophylaxis. Animal modeling has been a cornerstone of novel therapeutic development but has not produced reliable clinical therapies for prevention of adhesive small bowel obstruction. The purpose of this scoping review is to analyze animal models for abdominal adhesion generation by key considerations of external validity (i.e., fidelity, homology, and discrimination). METHODS: A literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews guidelines. Peer-reviewed publications were included that described the development or quality assessment of experimental animal models for abdominal adhesions with inclusion of a scoring system. Studies that focused on treatment evaluation, implantation of surgical devices, models of nonsurgical etiologies for abdominal adhesions, non-in vivo modeling, and investigations involving human subjects were excluded. RESULTS: Four hundred and fifteen (n = 415) articles were identified by prespecified search criteria. Of these, 13 studies were included for review. CONCLUSIONS: Translation of investigational therapeutics for abdominal adhesion prevention is dependent upon high-quality experimental animal models that reproduce the clinical adhesions seen in the operating room as a disease of the entire abdomen.

Clinical and Biological Perspectives on Noncanonical Esophageal Squamous Cell Carcinoma in Rare Subtypes.

Esophageal squamous cell carcinoma (ESCC) remains the most common malignancy of the esophagus worldwide. Environmental and lifestyle exposures such as alcohol and tobacco have been well defined in the pathogenesis of ESCC, acting in concert with cell intrinsic epigenomic, genomic and transcriptomic changes. However, a variety of nonenvironmental etiologies including Fanconi anemia, lichen planus, chronic mucocutaneous candidiasis, esophageal epidermoid metaplasia, epidermolysis bullosa, tylosis, esophageal atresia, and achalasia receive minimal attention despite a high risk of ESCC in these diseases. The goal of this review was to promote clinical recognition and suggest a diagnostic framework for earlier detection of ESCC in patients with these rare diseases. In all the discussed conditions, a change in symptoms should trigger a prompt endoscopic evaluation, and endoscopic surveillance programs with advanced imaging techniques and chromoendoscopy should be considered. Moreover, we leverage the convergence of these diseases on ESCC to identify common mechanisms underlying malignant transformation including aberrant proliferation, mucosal barrier dysfunction, increased inflammation, and genome instability. In this study, we summarize the clinical presentation, pathologic findings, potential screening strategies, and common mechanisms of malignant transformation associated with these rare diseases that drive ESCC.

Suicide by Ethyl Methacrylate Ingestion.

ABSTRACT: This case report characterizes a unique way in which suicide was accomplished through ingestion of chemicals typically used to create acrylic fingernails that resulted in death. Ethyl methacrylate and acrylic powder are commonly combined to form acrylic nails in nail salons. The process of applying acrylic nails utilizes each substance by mixing both before it typically solidifies within seconds of combining the two compounds. Ingestion of these compounds has not been previously described within the medical literature. The decedent was a nail technician at a local salon. He was found unresponsive in his yard which led to a 911 call. At the scene, a mostly empty 16-oz bottle of ethyl methacrylate, a chemical used at the salon where he worked, was found. At autopsy, the decedent's body had a strong chemical odor consistent with odors present at nail salons. Significant gastrointestinal tract damage was seen including discoloration within the esophagus, and the stomach contained a molded, hardened nail compound. The cause of death was ruled as complications of nail acrylic powder and liquid ethyl methacrylate ingestion. This case shows the unusual findings seen at autopsy from a decedent who committed suicide by ingestion of ethyl methacrylate with acrylic powder.