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The development of high-resolution mapping models for forest attributes based on remote sensing data combined with machine or deep learning techniques has become a prominent topic in the field of forest observation and monitoring. This has resulted in the availability of multiple, sometimes conflicting, sources of information, but, at face value, it also makes it possible to learn about forest attribute uncertainty through the joint interpretation of multiple models. This article seeks to endorse the latter by utilizing the Bayesian model averaging approach to diagnose and interpret the differences between predictions from different models. The predictions in our case are forest canopy height estimations for metropolitan France arising from five different models. An independent reference dataset, containing four different definitions of forest height (dominant, mean, maximum, and Lorey's) was established based on around 5500 plots of the French National Forest Inventory (NFI), distributed across the entire area of interest. In this study, we evaluate models with respect to their probabilities of correctly predicting measurements or estimations obtained from NFI plots, highlighting the spatial variability in respective model probabilities across the study area. We observed significant variability in these probabilities depending on the forest height definition used, implying that the different models inadvertently predict different types of canopy height. We also present the respective inter-model and intra-model variance estimations, enabling us to grasp where the employed models have comparable contributions but contrasting predictions. We show that topography has an important impact on the models spread. Moreover, we observed that the forest stand vertical structure, the dominant tree species, and the type of forest ownership systematically emerge as statistically significant factors influencing the model divergences. Finally, we observed that the fitted higher-order mixtures, which enabled the presented analyses, do not necessarily reduce bias or prevent the saturation of the predicted heights observed in the individual models.

Objectives: Anterior spinal fusion (ASF) presents unique challenges, including the proximity of critical anatomic structures. Previous reports have detailed vascular injuries during exposure/approach; however, it is not well-documented whether structural aortic pathology, such as aneurysm, dissection, atherosclerosis, aortitis, or aortic tumors, impacts postoperative outcomes following anterior approach to the spine for spinal fusion. Materials and Methods: Using the New York State Statewide Planning and Research Cooperative System, thoracolumbar ASF patients with a history of aneurysm, dissection, atherosclerosis, aortitis, or aortic tumors (APath) were identified and matched to patients with no aortic pathologies (No-APath). The two cohorts were compared at 90-day and 2-year follow-up for complications, readmissions, and revisions. Multivariate binary stepwise logistic regression identified independent predictors of these outcomes. Results: Ninety-nine and 64 patients were included at 90-day and 2-year follow-ups, respectively. APath and No-APath had comparable demographics. Through 90-day follow-up, both cohorts had similar vascular complications and overall complications. No-APath patients had higher surgical complications (11.1% vs. 0%, P = 0.021). At 2-year follow-up, cohorts had comparable vascular complications, overall complications, and all other outcomes (P > 0.05). Neither group was observed to require any revisions through 2-year follow-up. The presence of a structural aortic pathology was not associated with increased odds of incurring adverse outcomes at 90-day and 2-year follow-ups. Conclusions: Structural aortic compromise in the setting of thoracolumbar ASF did not predispose patients to adverse vascular, spinal-related, or medical/surgical complications, nor to anterior spinal or vascular revision or repair through 2-year follow-up. These results highlight the need for well-powered studies to further delineate the risk of anterior spinal surgery in this cohort of patients.

Temperature trends in the upper stratosphere, particularly above ∼ 45 km, are difficult to quantify due to a lack of observational data with high vertical resolution in this region that span multiple decades. The recent v7.3 upper-stratospheric (35–60 km) temperature data product from the Optical Spectrograph and InfraRed Imager System (OSIRIS) includes over 22 years of observations that can be used to estimate temperature trends. The trends in OSIRIS temperatures over 2005–2021 are compared to those from two other satellite limb instruments: Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) and Microwave Limb Sounder (MLS). We find that the upper stratosphere cooled by ∼ 0.5 to 1 K per decade during this period. Results from the three instruments are generally in agreement. By merging the OSIRIS observations with those from channel 3 of the Stratospheric Sounding Unit (SSU), we find that the stratosphere cooled at a rate of approximately −0.6 K per decade between 1979 and 2021 near 45 km, in agreement with earlier results based on SSU and MLS. The similarity between OSIRIS temperature trends and those from other records improves confidence in observed upper-stratospheric temperature changes over the last several decades.

We used Medicare data to identify >88,000 adults >65 years of age diagnosed and treated for Lyme disease during 2016–2019 in the United States. Most diagnoses occurred among residents of high-incidence states, in summer, and among men. Incidence of diagnoses was substantially higher than that reported through public health surveillance.

BACKGROUND:. Accurate assessment of oxygen delivery relative to oxygen demand is crucial in the care of a critically ill patient. The central venous oxygen saturation (Svo2) enables an estimate of cardiac output yet obtaining these clinical data requires invasive procedures and repeated blood sampling. Interpretation remains subjective and vulnerable to error. Recognition of patient’s evolving clinical status as well as the impact of therapeutic interventions may be delayed. OBJECTIVE:. The predictive analytics algorithm, inadequate delivery of oxygen (IDo2) index, was developed to noninvasively estimate the probability of a patient’s Svo2 to fall below a preselected threshold. DERIVATION COHORT:. A retrospective multicenter cohort study was conducted using data temporally independent from the design and development phase of the IDo2 index. VALIDATION COHORT:. A total of 20,424 Svo2 measurements from 3,018 critically ill neonates, infants, and children were retrospectively analyzed. Collected data included vital signs, ventilator data, laboratory data, and demographics. PREDICTION MODEL:. The ability of the IDo2 index to predict Svo2 below a preselected threshold (30%, 40%, or 50%) was evaluated for discriminatory power, range utilization, and robustness. RESULTS:. Area under the receiver operating characteristic curve (AUC) was calculated for each index threshold. Datasets with greater amounts of available data had larger AUC scores. This was observed across each configuration. For the majority of thresholds, Svo2 values were observed to be significantly lower as the IDo2 index increased. CONCLUSIONS:. The IDo2 index may inform decision-making in pediatric cardiac critical care settings by providing a continuous, noninvasive assessment of oxygen delivery relative to oxygen demand in a specific patient. Leveraging predictive analytics to guide timely patient care, including support for escalation or de-escalation of treatments, may improve care delivery for patients and clinicians.

Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Methods Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan−Meier method. Results Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, treatment and age. Lower DLCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21–2.02) per 10 units lower (p

Background: In 2022, the catchment area of the Fred Hutchinson/University of Washington/Seattle Children’s Cancer Consortium (the Consortium) grew from 13-counties in Western Washington State to include all 39 counties in Washington.Methods: Widening the catchment area provided new opportunities for the Consortium to monitor the cancer burden, identify cancer-related health disparities, use a bidirectional approach to develop cancer focused programming, and facilitate research in clinical and community settings.Results: In this commentary, we describe the exploratory process of catchment area change led by the Consortium’s Office of Community Outreach and Engagement and new initiatives that followed that growth.Discussion: We hope that by sharing the ongoing, data-driven community engagement approach in the Consortium’s current, statewide catchment area, our experience will be of value to other cancer centers looking to engage with communities and develop bidirectional partnerships in new areas.

Background: Although several surgical landmarks have been proposed to localize the recurrent laryngeal nerve (RLN), there is still no reliable landmark. Aims: To validate the reliability of a novel reference point at the intersection of the inferior border of the cricopharyngeal muscle and the inferior cornu of thyroid cartilage for locating the RLN. Study Design: Cadaver dissection study in the academic department of otolaryngology-head and neck surgery. Methods: Sixty-four RLNs in cadavers were assessed, and measurements of different surgical landmarks in conjunction with the proposed surgical landmark were obtained. Descriptive statistics, Pearson’s chi-squared test, and Student’s t-test were performed to analyze the data using GraphPad Prism (version 9.4.1; Dotmatics, Boston, Massachusetts, USA). Results: The average distance from the proposed landmark to the RLN was 2.3 ± 0.85 mm. The RLN was located just posterior to the reference point in 95.31% of the cadavers. The RLN passed under the inferior constrictor muscle in 90.63% of the cadavers. There was no statistically significant difference between right- and left-sided RLNs in terms of their relation with the reference point. Conclusion: The proposed reference point can be used as a reliable landmark to locate the RLN. This reference point may help surgeons during difficult thyroidectomy surgeries by providing an additional anatomical landmark.

Abstract The CEPI Centralized Laboratory Network implemented key steps in the transfer and monitoring of the developed immunological SARS-CoV-2 assays to ensure standardization across all the facilities of the network. This comprehensive evaluation reinforces the reliability of the generated data and establishes a solid foundation for a standardized approach, enabling precise inter-laboratory comparisons and contributing to the overall integrity of our network’s clinical results. Herein, we will provide a brief elaboration on the specific measures and procedures implemented to standardize the transfer of assays across our network.

Abstract Interleukin-9 (IL-9) is a multifunctional cytokine with roles in a broad cross-section of human diseases. Like many cytokines, IL-9 is transcriptionally regulated by a group of noncoding regulatory elements (REs) surrounding the IL9 gene. These REs modulate IL-9 transcription by forming 3D loops that recruit transcriptional machinery. IL-9-promoting transcription factors (TFs) can bind REs to increase locus accessibility and permit chromatin looping, or they can be recruited to already accessible chromatin to promote transcription. Ample mechanistic and genome-wide association studies implicate this interplay between IL-9-modulating TFs and IL9 cis-REs in human physiology, homeostasis, and disease.

Background: Rupture of the pectoralis major is most commonly seen with eccentric contraction mechanisms, and surgical options in the setting of acute tear include direct repair, endocortical buttons, suture anchors, and transosseous tunnel fixation. This technique video will detail repair using a unicortical endobutton fixation construct. Indications: Surgical repair is indicated for acute, complete pectoralis major tears; incomplete tears involving rupture of the sternal head with intact clavicular head; and tears in the young, active, high-demand demographic. Delay in diagnosis increases the risk of tendon retraction and fatty atrophy. Recent literature has shown that acute repair is superior to chronic repair in functional outcome, pain relief, and overall cosmesis. Technique Description: A beach-chair position and a deltopectoral approach are used to identify and mobilize the torn and retracted sternal head of the pectoralis major. A No. 2 SutureTape is then passed through the disrupted sternal head in a Krackow fashion to allow for a 6-strand repair. Two of the suture strands are then shuttled through the endocortical button. A drill is used to create a corticectomy for endobutton placement, which is secured into place by sequentially tightening each limb. Two additional endobuttons are placed in a similar fashion to complete the construct. Results: Outcomes studies regarding patients with pectoralis major tendon ruptures who underwent endocortical button fixation reveal that 83% of patients had good or excellent outcomes in a recent systematic review. Another study showed no significant difference in functional outcomes, return to activity, or complication rate with endocortical button fixation compared with other mechanisms of fixation. Discussion/Conclusion: Unicortical endobutton fixation can provide another fixation strategy for acute pectoralis major tears in young, active high-demand individuals. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

The cause of the transition from Mesozoic and early Cenozoic crustal shortening to later extension in the western United States is debated. In many parts of the extant Sevier hinterland, now the Basin and Range Province, the sedimentary sections that provide the most direct record of that transition remain poorly studied and lack meaningful age control. In this paper, we present field characterization supported by U-Pb detrital zircon and 40Ar/39Ar feldspar ages for ten sections across southern Nevada. We describe a newly identified basin, here named the Fallout Hills basin, which preserves >1.0 km of sedimentary deposits as old as middle Eocene, ca. 48 Ma. Deposition occurred during the 20 m.y. (million years) before the 27.60 ± 0.03 Ma Monotony Tuff blanketed much of south-central Nevada, based on 47.6 Ma and younger detrital zircon maximum depositional ages (MDAs) from near the Pintwater and Spotted Ranges. Elsewhere in southern Nevada, prevolcanic Cenozoic strata commonly form thinner (~100 m), isolated exposures that yield detrital zircon MDAs ≤10 m.y. older than (and in some cases essentially the same age as) the ca. 27–28 Ma ignimbrites that cap the sections. A variable but overall upward-fining facies pattern is observed in both the Fallout Hills basin and the thinner sections. These localized patterns imply topographic changes that are unlikely to reflect plate-scale processes and are not consistent with large-magnitude extension. Instead, variable uplift due to magmatism combined with antecedent topographic relief from thrust faulting and subsequent erosion likely provided accommodation for these deposits.

IntroductionCompanion animals offer a unique opportunity to investigate risk factors and exposures in our shared environment. Passive sampling techniques have proven effective in capturing environmental exposures in dogs and humans.MethodsIn a pilot study, we deployed silicone monitoring devices (tags) on the collars of a sample of 15 dogs from the Dog Aging Project Pack cohort for a period of 120 h (5 days). We extracted and analyzed the tags via gas chromatography–mass spectrometry for 119 chemical compounds in and around participants’ homes.ResultsAnalytes belonging to the following chemical classes were detected: brominated flame retardants (BFRs), organophosphate esters (OPEs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), pesticides, phthalates, and personal care products. The types and amounts of analytes detected varied substantially among participants.DiscussionData from this pilot study indicate that silicone dog tags are an effective means to detect and measure chemical exposure in and around pet dogs’ households. Having created a sound methodological infrastructure, we will deploy tags to a geographically diverse and larger sample size of Dog Aging Project participants with a goal of further assessing geographic variation in exposures.

Abstract Farmers need accurate estimates of winter cover crop biomass to make informed decisions on termination timing or to estimate potential release of nitrogen from cover crop residues to subsequent cash crops. Utilizing data from an extensive experiment across 11 states from 2016 to 2020, this study explores the most reliable predictors for determining cereal rye cover crop biomass at the time of termination. Our findings demonstrate a strong relationship between early‐season and late‐season cover crop biomass. Employing a random forest model, we predicted late‐season cereal rye biomass with a margin of error of approximately 1,000 kg ha−1 based on early‐season biomass, growing degree days, cereal rye planting and termination dates, photosynthetically active radiation, precipitation, and site coordinates as predictors. Our results suggest that similar modeling approaches could be combined with remotely sensed early‐season biomass estimations to improve the accuracy of predicting winter cover crop biomass at termination for decision support tools. Core Ideas Cereal rye winter cover crop biomass modeled on data from 35 site‐years. We found a strong relationship between early and late‐season biomass. Random forest model with early‐season biomass and weather data performed well. Similar approach could improve decision support tools for cover crop management.

Purpose: Surgical fixation of olecranon fractures can lead to soft-tissue complications and return to the operating room for hardware removal. While some risk factors of complications after olecranon fracture fixation have been described, the effects of fixation timing on complications and reoperation have not been evaluated. The purpose of the present study was to assess whether the timing of olecranon fracture fixation affects complication and reoperation rates. Methods: All patients who underwent olecranon fracture open reduction and internal fixation at a single level 1 trauma center from January 2012 to February 2022 were included in the study. A retrospective review was performed to evaluate patients for inclusion and to identify patient demographic factors, medical comorbidities, concomitant injuries, mechanism of injury, and time to fixation. Operative and clinical notes were evaluated to identify fixation type and outcomes of interest. Patients were stratified into early, standard, and delayed fixation groups (0-3 days, 4–14 days, and >14 days, respectively) for independent analyses, and Fisher’s exact test was used to identify differences in complications and reoperations between groups. Multivariate analysis was used to assess associations between patient demographic factors, complication rates, and time to surgery. Results: A total of 97 patients met inclusion criteria of having an olecranon open reduction and internal fixation and had a minimum follow-up of at least 10 weeks, with an average follow-up of 7.1 months. The average time to surgery in the overall cohort was 9.3 days. There were no differences in the number of total complications and rate of reoperation among the three cohorts. Smoking was found to be significantly associated with total complications, while open fracture was significantly associated with reoperation. Polytrauma and open fracture were significantly associated with earlier operation, while smoking was significantly associated with delayed fixation. Conclusions: The timing of fixation of displaced olecranon fractures does not significantly increase the rate of early complications or reoperation. Type of study/level of evidence: Symptom Prevalence Study III.

Objectives: Limited data on performing bilateral pulmonary artery banding (BPAB) before stage 1 Norwood procedure suggest that some patients may benefit through the postponement of the major cardiopulmonary bypass procedure. The objective of this study was to evaluate the effectiveness of BPAB in the surgical management of high-risk patients with hypoplastic left heart syndrome (HLHS). Methods: A retrospective review of all high-risk neonates with HLHS who underwent BPAB at our institution was performed. No patients, including those with intact or highly restrictive atrial septum (IAS), were excluded. Results: Between October 2015 and April 2021, 49 neonates with HLHS (including 6 with IAS) underwent BPAB, 40 of whom progressed to the Norwood procedure. Risk factors for not progressing to the Norwood procedure after BPAP include low birth weight (P = .043), the presence of multiple extracardiac anomalies (P = .005), and the presence of genetic disorders (P = .028). Operative mortality was 7.5% (3/40). IAS was associated with operative mortality (P = .022). Conclusions: The strategy of BPAB prestage 1 Norwood procedure was successful in identifying at-risk patients and improving Norwood survival. Although not all patients will need this hybrid approach, a significant number can be expected to benefit from this tactic. These results support the need for a substantial hybrid strategy, in addition to a primary stage 1 Norwood surgical strategy, in the management of HLHS.

The contribution of forests to carbon storage and biodiversity conservation highlights the need for accurate forest height and biomass mapping and monitoring. In France, forests are managed mainly by private owners and divided into small stands, requiring 10 to 50 m spatial resolution data to be correctly separated. Further, 35 % of the French forest territory is covered by mountains and Mediterranean forests which are managed very extensively. In this work, we used a deep-learning model based on multi-stream remote-sensing measurements (NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission and ESA's Copernicus Sentinel-1 and Sentinel-2 satellites) to create a 10 m resolution canopy height map of France for 2020 (FORMS-H). In a second step, with allometric equations fitted to the French National Forest Inventory (NFI) plot data, we created a 30 m resolution above-ground biomass density (AGBD) map (Mg ha−1) of France (FORMS-B). Extensive validation was conducted. First, independent datasets from airborne laser scanning (ALS) and NFI data from thousands of plots reveal a mean absolute error (MAE) of 2.94 m for FORMS-H, which outperforms existing canopy height models. Second, FORMS-B was validated using two independent forest inventory datasets from the Renecofor permanent forest plot network and from the GLORIE forest inventory with MAE of 59.6 and 19.6 Mg ha−1, respectively, providing greater performance than other AGBD products sampled over France. Finally, we compared FORMS-V (for volume) with wood volume estimations at the ecological region scale and obtained an R2 of 0.63 with an MAE of 30 m3 ha−1. These results highlight the importance of coupling remote-sensing technologies with recent advances in computer science to bring material insights to climate-efficient forest management policies. Additionally, our approach is based on open-access data having global coverage and a high spatial and temporal resolution, making the maps reproducible and easily scalable. FORMS products can be accessed from https://doi.org/10.5281/zenodo.7840108 (Schwartz et al., 2023).

Borrelia miyamotoi, transmitted by Ixodes spp. ticks, was recognized as an agent of hard tick relapsing fever in the United States in 2013. Nine state health departments in the Northeast and Midwest have conducted public health surveillance for this emerging condition by using a shared, working surveillance case definition. During 2013–2019, a total of 300 cases were identified through surveillance; 166 (55%) were classified as confirmed and 134 (45%) as possible. Median age of case-patients was 52 years (range 1–86 years); 52% were male. Most cases (70%) occurred during June–September, with a peak in August. Fever and headache were common symptoms; 28% of case-patients reported recurring fevers, 55% had arthralgia, and 16% had a rash. Thirteen percent of patients were hospitalized, and no deaths were reported. Ongoing surveillance will improve understanding of the incidence and clinical severity of this emerging disease.

The frequency and intensity of summer droughts and heat waves in Western Europe have been increasing, raising concerns about the emergence of fire hazard in less fire-prone areas. This exposure of old-growth forests hosting unadapted tree species may cause disproportionately large biomass losses compared to those observed in frequently burned Mediterranean ecosystems. Therefore, analyzing fire seasons from the perspective of exposed burned areas alone is insufficient; we must also consider impacts on biomass loss. In this study, we focus on the exceptional 2022 summer fire season in France and use very high-resolution (10 m) satellite data to calculate the burned area, tree height at the national level, and subsequent ecological impact based on biomass loss during fires. Our high-resolution semi-automated detection estimated 42 520 ha of burned area, compared to the 66 393 ha estimated by the European automated remote sensing detection system (EFFIS), including 48 330 ha actually occurring in forests. We show that Mediterranean forests had a lower biomass loss than in previous years, whereas there was a drastic increase in burned area and biomass loss over the Atlantic pine forests and temperate forests. High biomass losses in the Atlantic pine forests were driven by the large burned area (28 600 ha in 2022 vs. 494 ha yr−1 in 2006–2021 period) but mitigated by a low exposed tree biomass mostly located on intensive management areas. Conversely, biomass loss in temperate forests was abnormally high due to both a 15-fold increase in burned area compared to previous years (3300 ha in 2022 vs. 216 ha in the 2006–2021 period) and a high tree biomass of the forests which burned. Overall, the biomass loss (i.e., wood biomass dry weight) was 0.25 Mt in Mediterranean forests and shrublands, 1.74 Mt in the Atlantic pine forest, and 0.57 Mt in temperate forests, amounting to a total loss of 2.553 Mt, equivalent to a 17 % increase of the average natural mortality of all French forests, as reported by the national inventory. A comparison of biomass loss between our estimates and global biomass/burned areas data indicates that higher resolution improves the identification of small fire patches, reduces the commission errors with a more accurate delineation of the perimeter of each fire, and increases the biomass affected. This study paves the way for the development of low-latency, high-accuracy assessment of biomass losses and fire patch contours to deliver a more informative impact-based characterization of each fire year.

Background Predictive scales have been used to prognosticate long-term outcomes of traumatic brain injury (TBI), but gaps remain in predicting mortality using initial trauma resuscitation data. We sought to evaluate the association of clinical variables collected during the initial resuscitation of intubated pediatric severe patients with TBI with in-hospital mortality.Methods Intubated pediatric trauma patients

Abstract Background Emotional eating is a complex problem fostering obesity and resulting from maladaptive emotion regulation. Traditional behavioural weight loss interventions have shown insignificant effect. They can be improved by targeting the specific needs of individuals with emotional eating. Objective The current study explored a tailored online approach with the aim to positively influence affect (positive and negative) and emotion regulation by applying one of three exercises: body scan, opposite action, and positive reappraisal. Design An embedded mixed-method design (questionnaire data (t0, t1, t2) and perceived usefulness of exercises in t2) was used to evaluate the effects of a two-week online quasi-experimental pilot study. Subjects/setting In total, 80 participants with self-reported emotional eating difficulties (DEBQ-E; M emo = 3.48, SD = .64, range 1.62–4.92) finished baseline measurements; 15 completed the intervention. The study sample was predominantly female (95%), from 18 till 66 (M age = 38,0 ± SD = 14.25). Results Participants reported that the exercises helped them to pay attention to their physical sensations, and to see positive aspects in negative matters. The exercises were considered difficult by the participants, with too little explanation, and dull, due to minor variation. The observed changes revealed small, and moreover, not significant improvements of the three exercises on positive and negative affect and overall emotion dysregulation. Although the quantitative results did not reach significance, the qualitative data highlighted which aspects of the tailored exercises may have contributed to mood and emotion regulation outcomes. A notable observation in the present study is the substantial dropout rate, with the number of participants decreasing from 80 at baseline (T0) to 15 at the post-intervention stage (T2). Conclusions Future studies should identify tailored online exercises in emotion regulation skills in more detail and explore the contexts in which they are most effective in a personalized virtual coach virtual coach to be developed for individuals with emotional eating. Given the high dropout rate, more emphasis should be given to a proper presentation of the exercises, as well as more explanation of their usefulness and how to perform them.

Abstract Background Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC). Methods The analyses were conducted by pooling data from three case–control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face‐to‐face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models. Results Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively. Conclusion In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.

Introduction Soft tissue defects are a devastating complication of prosthetic joint infections (PJI) after total knee arthroplasty (TKA). Rotational flaps are commonly utilized to address these defects with variable reports of success. This study aimed to identify predictors of poor outcomes in rotational muscle flap placement after prosthetic knee infections. The authors hypothesized that outcomes may vary based on infecting pathogen and treatment characteristics. Methods 44 cases of rotational muscle flaps for prosthetic knee infection were retrospectively evaluated at a tertiary referral hospital from 2007 to 2020. Muscle flap types included 39 medial and four lateral gastrocnemius, and one anterior tibialis. Minimum follow-up was 1 year (median: 3.4 years). Primary outcome was flap-related complications. Secondary outcomes included recurrent infection requiring additional surgery, final joint outcomes, and mortality. Results One-year complication-free flap survivorship was 83.9%, recurrent infection-free survivorship was 65.7%, and amputation-free survivorship was 79%. Multivariable cox regression revealed that rheumatoid arthritis diagnosis (HR: 3.4; p = .028) and methicillin-resistant Staphylococcus aureus -positive culture (HR: 4.0; p = .040) had increased risk, while Coagulase-negative Staphylococcus infections had reduced risk for recurrent or persistent infection (HR: 0.2; p = .023). Final joint outcome was retained TKA implant in 18 (40.9%), amputation in 15 (34.1%) patients, and definitive treatment with articulating spacer in 10 (22.7%). 5-years survivorship from death was 71.4%. Conclusion Rotational muscle flaps for soft tissue coverage of the knee are often performed in limb salvage situations with poor survivorship from flap complications, reinfections, and amputation. When considering surgical options for limb salvage, patients should be counseled on these risks.

Abstract Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of recombinant IL2 (rIL2), an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, CD4 + effector T cells (Teff), and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the rIL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.

IntroductionLarge scale data on the prevalence of diverse medical conditions among dog breeds in the United States are sparse. This cross-sectional study sought to estimate the lifetime prevalence of medical conditions among US dogs and to determine whether purebred dogs have higher lifetime prevalence of specific medical conditions compared to mixed-breed dogs.MethodsUsing owner-reported survey data collected through the Dog Aging Project (DAP) Health and Life Experience Survey for 27,541 companion dogs, we identified the 10 most commonly reported medical conditions in each of the 25 most common dog breeds within the DAP cohort. Lifetime prevalence estimates of these medical conditions were compared between mixed-breed and purebred populations. The frequency of dogs for whom no medical conditions were reported was also assessed within each breed and the overall mixed-breed and purebred populations.ResultsA total of 53 medical conditions comprised the top 10 conditions for the 25 most popular breeds. The number of dogs for whom no medical conditions were reported was significantly different (p = 0.002) between purebred (22.3%) and mixed-breed dogs (20.7%). The medical conditions most frequently reported within the top 10 conditions across breeds were dental calculus (in 24 out of 25 breeds), dog bite (23/25), extracted teeth (21/25), osteoarthritis (15/25), and Giardia (15/25).DiscussionPurebred dogs in the DAP did not show higher lifetime prevalence of medical conditions compared to mixed-breed dogs, and a higher proportion of purebred dogs than mixed-breed dogs had no owner-reported medical conditions. Individual breeds may still show higher lifetime prevalence for specific conditions.

BackgroundTucatinib is an oral human epidermal growth factor receptor 2 (HER2)-directed therapy approved in combination with trastuzumab and capecitabine for use in patients with previously treated HER2+ metastatic breast cancer (MBC) with/without brain metastases (BM). To inform clinical decision-making, it is important to understand tucatinib use in real-world clinical practice. We describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib treatment in the real-world setting.MethodsThis retrospective cohort study included patients diagnosed with HER2+ MBC (January 2017-December 2022) who received tucatinib treatment in a nationwide, de-identified electronic health record–derived metastatic breast cancer database. Patient demographics and clinical characteristics were described at baseline (prior to tucatinib initiation). Key outcomes included real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS).ResultsOf 3,449 patients with HER2+ MBC, 216 received tucatinib treatment (n=153 with BM; n=63 without BM) and met inclusion criteria. Median (range) age of patients was 56 (28-84) years, 57.9% were White, and 68.5% had Eastern Cooperative Oncology Group performance status ≤1. Median (IQR) follow-up from start of tucatinib treatment was 12 (6-18) months. Among all patients who received tucatinib treatment, median (95% CI) rwTTD was 6.5 (5.4-8.8) months with 39.8% and 21.4% remaining on treatment at 12 and 24 months, respectively. Median (95% CI) rwTTNT was 8.7 (6.8-10.7) months. Patients who received the approved tucatinib triplet combination after ≥1 HER2-directed regimen in the metastatic setting had a similar median (95% CI) rwTTD (any line: 8.1 [5.7-9.5] months; second-line (2L) and third-line (3L): 9.4 [6.3-14.1] months) and rwTTNT (any line: 8.8 [7.1-11.8] months; 2L and 3L: 9.8 [6.8-14.1] months) to the overall population. Overall, median (95% CI) rwOS was 26.6 (20.2-not reached [NR]) months, with similar findings for patients who received the tucatinib triplet (26.1 [18.8-NR] months) and was NR in the subgroup limited to the 2L/3L population.ConclusionTucatinib treatment in the real-world setting was associated with a similar median rwTTD, rwTTNT, and rwOS as in the pivotal HER2CLIMB trial, with particular effectiveness in patients in the 2L/3L setting. These results highlight the importance of earlier use of tucatinib in HER2+ MBC.

Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.

Abstract Canine cognitive dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP) (n = 15,019). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and receiver operating curve (ROC) analysis. When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.

Adoptive T cell immunotherapy has been used to restore immunity against multiple viral targets in immunocompromised patients after bone-marrow transplantation and has been proposed as a strategy for preventing coronavirus 2019 (COVID-19) in this population. Ideally, expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-virus-specific T cells (CSTs) should demonstrate marked cell expansion, T cell specificity, and CD8+ T cell skewing prior to adoptive transfer. However, current methodologies using IL-4 + IL-7 result in suboptimal specificity, especially in CD8+ cells. Using a microexpansion platform, we screened various cytokine cocktails (IL-4 + IL-7, IL-15, IL-15 + IL-4, IL-15 + IL-6, and IL-15 + IL-7) for the most favorable culture conditions. IL-15 + IL-7 optimally balanced T cell expansion, polyfunctionality, and CD8+ T cell skewing of a final therapeutic T cell product. Additionally, the transcriptomes of CD4+ and CD8+ T cells cultured with IL-15 + IL-7 displayed the strongest induction of antiviral type I interferon (IFN) response genes. Subsequently, microexpansion results were successfully translated to a Good Manufacturing Practice (GMP)-applicable format where IL-15 + IL-7 outperformed IL-4 + IL-7 in specificity and expansion, especially in the desirable CD8+ T cell compartment. These results demonstrate the functional implications of IL-15-, IL-4-, and IL-7-containing cocktails for therapeutic T cell expansion, which could have broad implication for cellular therapy, and pioneer the use of RNA sequencing (RNA-seq) to guide viral-specific T cell (VST) product manufacturing.

Introduction:Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events.Methods:Seventeen client-owned dogs aged 6–10 years, weighing 18–36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks.Results:There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04).Discussion:While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events.