Targeting both GD2 and B7-H3 using bispecific antibody improves tumor selectivity for GD2-positive tumors.

Objectives: Disialoganglioside 2 (GD2), overexpressed by cancers such as melanoma and neuroblastoma, is a tumor antigen for targeted therapy. The delivery of conventional IgG antibody technologies targeting GD2 is limited clinically by its co-expression on nerves that contributes to toxicity presenting as severe neuropathic pain. To improve the tumor selectivity of current GD2-targeting approaches, a next-generation bispecific antibody targeting GD2 and B7-H3 (CD276) was generated. Methods: Differential expression of human B7-H3 (hB7-H3) was transduced into GD2+ B78 murine melanoma cells and confirmed by flow cytometry. We assessed the avidity and selectivity of our GD2-B7-H3 targeting bispecific antibodies (INV34-6, INV33-2, and INV36-6) towards GD2+/hB7-H3- B78 cells relative to GD2+/hB7-H3+ B78 cells using flow cytometry and competition binding assays, comparing results an anti-GD2 antibody (dinutuximab, DINU). The bispecific antibodies, DINU, and a non-targeted bispecific control (bsAb CTRL) were conjugated with deferoxamine for radiolabeling with Zr-89 (t1/2 = 78.4 h). Using positron emission tomography (PET) studies, we evaluated the in vivo avidity and selectivity of the GD2-B7-H3 targeting bispecific compared to bsAb CTRL and DINU using GD2+/hB7-H3+ and GD2+/hB7-H3- B78 tumor models. Results: Flow cytometry and competition binding assays showed that INV34-6 bound with high avidity to GD2+/hB7-H3+ B78 cells with high avidity but not GD2+/hB7-H3+ B78 cells. In comparison, no selectivity between cell types was observed for DINU. PET in mice bearing the GD2+/hB7-H3- and GD2+/hB7-H3+ B78 murine tumor showed similar biodistribution in normal tissues for [89Zr]Zr-Df-INV34-6, [89Zr]Zr-Df-bsAb CTRL, and [89Zr]Zr-Df-DINU. Importantly, [89Zr]Zr-Df-INV34-6 tumor uptake was selective to GD2+/hB7-H3+ B78 over GD2+/hB7-H3- B78 tumors, and substantially higher to GD2+/hB7-H3+ B78 than the non-targeted [89Zr]Zr-Df-bsAb CTRL control. [89Zr]Zr-Df-DINU displayed similar uptake in both GD2+ tumor models, with uptake comparable to [89Zr]Zr-Df-INV34-6 in the GD2+/hB7-H3+ B78 model. Conclusion: The GD2-B7-H3 targeting bispecific antibodies successfully improved selectivity to cells expressing both antigens. This approach should address the severe toxicities associated with GD2-targeting therapies by reducing off-tumor GD2 binding in nerves. Continued improvements in bispecific antibody technologies will continue to transform the therapeutic biologics landscape.

Outcomes of Visceral Arterial Interposition Graft Reconstruction for Locally Advanced Pancreatic Cancer.

OBJECTIVE: The aim of this study is to determine perioperative outcomes and the patency of interposition conduits for visceral arterial reconstruction in this setting. SUMMARY BACKGROUND DATA: Visceral arterial encasement in locally advanced pancreatic cancer was historically a contraindication for surgery. With modern effective neoadjuvant strategies, our recent experience has made advanced vascular resection and reconstruction feasible in selected patients. METHODS: A retrospective review was performed of patients undergoing pancreatic tumor resection with en bloc arterial resection and interposition revascularization between 6/2002-10/2022. Endpoints included graft patency, vascular-related complications, reinterventions, morbidity, and mortality. RESULTS: Visceral arterial reconstruction with interposition grafting was performed in 111 patients undergoing en bloc arterial resections for pancreatic cancer. Graft types included autologous arterial conduits (n=66, 58 superficial femoral artery (SFA) and 8 splenic artery), cryopreserved arterial allografts (n=24), autologous saphenous veins (n=12), synthetic conduits (n=8), and composite autologous artery and synthetic (n=1). Perioperative 90-day mortality decreased significantly over time to 5% in the last six years. Vascular complications related to arterial reconstruction occurred in 11% (n=12) and included pseudoaneurysm (n=6), graft thrombus (n=2), stenosis requiring reintervention (n=2), hepatic failure (n=1), and hepatic and intestinal ischemia (n=1). Nine (8%) patients underwent vascular-related reinterventions. After median follow-up of 17-months, primary patency was 81% for the entire cohort and was highest in the SFA group (95%). The donor limb/harvest site complication rate was 8% with 100% primary patency. CONCLUSION: Visceral arterial resection with interposition reconstruction for locally advanced pancreatic cancer can be performed with acceptable vascular morbidity and durable patency. Autologous SFA was the most suitable conduit for reconstructions in our experience, with highest primary patency.

The construct validity of attitudes toward sex offenders (ATS) scale: ATS is more strongly linked to the acceptance of sex offenders than other offenders or non-offenders.

Negative attitudes toward offenders may hinder the rehabilitation process. The present study examines the relationship between attitudes toward sex offenders and stated acceptance of offenders and non-offenders into various aspects of daily life. Sixty female members of the public (18-50 years old, UK residents, recruited by word of mouth and via social media) completed an attitudes towards sex offenders (ATS) scale and indicated for each of eight vignettes describing ex-offenders and non-offenders whether they would accept them in various situations (housing, employment, day-to-day activities). Results indicate that in this group of female participants, harsher attitudes toward sex offenders are associated with lower acceptance of sex offenders (around 50% less acceptance) and other offenders (around 25% less acceptance), but not non-offenders, suggesting a tight coupling between attitudes and acceptance. The observed coupling between attitudes toward sex offenders and acceptance of offenders suggests that it will be difficult to change one without changing the other.

Different roads, same destination: The shared future of plant ecophysiology and ecohydrology.

Terrestrial water fluxes are substantially mediated by vegetation, while the distribution, growth, health, and mortality of plants are strongly influenced by the availability of water. These interactions, playing out across multiple spatial and temporal scales, link the disciplines of plant ecophysiology and ecohydrology. Despite this connection, the disciplines have provided complementary, but largely independent, perspectives on the soil-plant-atmosphere continuum since their crystallization as modern scientific disciplines in the late 20th century. This review traces the development of the two disciplines, from their respective origins in engineering and ecology, their largely independent growth and maturation, and the eventual development of common conceptual and quantitative frameworks. This common ground has allowed explicit coupling of the disciplines to better understand plant function. Case studies both illuminate the limitations of the disciplines working in isolation, and reveal the exciting possibilities created by consilience between the disciplines. The histories of the two disciplines suggest opportunities for new advances will arise from sharing methodologies, working across multiple levels of complexity, and leveraging new observational technologies. Practically, these exchanges can be supported by creating shared scientific spaces. This review argues that consilience and collaboration are essential for robust and evidence-based predictions and policy responses under global change.

Assessing the stops framework for coping with intraoperative errors: Evidence of efficacy, hints of hubris, and a bridge to abridging burnout.

BACKGROUND: Answering calls in the literature, we developed and introduced an evidence-based tool for surgeons facing errors in the operating room: the STOPS framework (stop, talk to you team, obtain help, plan, succeed). The purpose of this research was to assess the impact of presenting this psychological tool on resident coping in the operating room and the related outcome of burnout while examining sex differences. METHODS: In a natural experiment, general surgery residents were invited to attend 2 separate educational conferences regarding coping with errors in the operating room. Three months later, all residents were asked to fill out a survey assessing their coping in the operating room, level of burnout, and demographics. We assessed the impact of the educational intervention by comparing those who attended the coping conferences with those who did not attend. RESULTS: Thirty-five residents responded to the survey (65% response rate, 54% female respondents, 49% junior residents). Our hypothesized moderated mediation model was supported. Sex was found to moderate the impact of the STOPS framework-female residents who attended the coping educational conference reported higher coping self-efficacy, whereas attendance had no statistically significant impact on male levels of coping self-efficacy. In turn, higher coping self-efficacy was associated with lower levels of burnout. CONCLUSION: Our results suggest that there is evidence of efficacy in this instruction-female residents presented this material report higher levels of coping in the operating room compared to those who did not receive the framework. Further, increase in coping ability was associated with reduced levels of burnout for both genders.

Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid.

INTRODUCTION: Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types. METHODS: We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases. RESULTS: Protein co-expression network analysis identified unique cerebrovascular modules significantly correlated with amyloid plaques, cerebrovascular amyloid angiopathy (CAA), and/or tau pathology. The protein products within AD genetic risk loci were concentrated within cerebrovascular modules. The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with cerebrovascular network highlighted a significant increase of matrisome proteins, SMOC1 and SMOC2, in CSF, plasma, and brain. DISCUSSION: These findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases.

Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial and ethnic groups. Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS). Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals. Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.

Lead poisoning of raptors: state of the science and cross-discipline mitigation options for a global problem.

Lead poisoning is an important global conservation problem for many species of wildlife, especially raptors. Despite the increasing number of individual studies and regional reviews of lead poisoning of raptors, it has been over a decade since this information has been compiled into a comprehensive global review. Here, we summarize the state of knowledge of lead poisoning of raptors, we review developments in manufacturing of non-lead ammunition, the use of which can reduce the most pervasive source of lead these birds encounter, and we compile data on voluntary and regulatory mitigation options and their associated sociological context. We support our literature review with case studies of mitigation actions, largely provided by the conservation practitioners who study or manage these efforts. Our review illustrates the growing awareness and understanding of lead exposure of raptors, and it shows that the science underpinning this understanding has expanded considerably in recent years. We also show that the political and social appetite for managing lead ammunition appears to vary substantially across administrative regions, countries, and continents. Improved understanding of the drivers of this variation could support more effective mitigation of lead exposure of wildlife. This review also shows that mitigation strategies are likely to be most effective when they are outcome driven, consider behavioural theory, local cultures, and environmental conditions, effectively monitor participation, compliance, and levels of raptor exposure, and support both environmental and human health.

Synthesis and Evaluation of a Novel PET Radioligand for Imaging Glutaminyl Cyclase Activity as a Biomarker for Detecting Alzheimer's Disease.

Several new lines of research have demonstrated that a significant number of amyloid-ß peptides found in Alzheimer's disease (AD) are truncated and undergo post-translational modification by glutaminyl cyclase (QC) at the N-terminal. Notably, QC's products of Abeta-pE3 and Abeta-pE11 have been active targets for investigational drug development. This work describes the design, synthesis, characterization, and in vivo validation of a novel PET radioligand, [18F]PB0822, for targeted imaging of QC. We report herein a simplified and robust chemistry for the synthesis of the standard compound, [19F]PB0822, and the corresponding [18F]PB0822 radioligand. The PET probe was developed with 99.9% radiochemical purity, a molar activity of 965 Ci.mmol-1, and an IC50 of 56.3 nM, comparable to those of the parent PQ912 inhibitor (62.5 nM). Noninvasive PET imaging showed that the probe is distributed in the brain 5 min after intravenous injection. Further, in vivo PET imaging with [18F]PB0822 revealed that AD 5XFAD mice harbor significantly higher QC activity than WT counterparts. The data also suggested that QC activity is found across different brain regions of the tested animals.

Consumption of ß-Caryophyllene Increases the Mating Success of Bactrocera zonata Males (Diptera: Tephritidae).

The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae), is an economically important polyphagous quarantine pest of horticultural crops endemic to South and Southeast Asia. Methyl eugenol (ME), a naturally occurring phenylpropanoid, is a male attractant used to lure and (when mixed with an insecticide) annihilate the males from the wild population, a method of pest control termed the male annihilation technique (MAT). ME is reported to enhance the mating success of sterile males of Bactrocera spp., which is critical for enhancing the effectiveness of the sterile insect technique (SIT). The suppressed response of ME-treated males to ME-baited traps/devices allows the simultaneous application of the MAT and SIT, increasing the efficiency of area-wide integrated pest management (AW-IPM) programs. However, ME treatment in sterile males in SIT facilities is logistically difficult. ß-caryophyllene (BCP) is a widely occurring, safer plant compound and is considered suitable for treating males in SIT facilities. Here, we demonstrate that BCP feeding enhanced B. zonata male mating success to the same extent as ME feeding. Feeding on BCP suppressed the male's subsequent attraction to ME-baited traps, but not to the same degree as feeding on ME. The results are discussed and BCP is suggested as an alternative to ME for the concurrent use of the MAT and SIT.

Implications and late outcomes of type II endoleaks after endovascular aneurysm repair.

OBJECTIVE: Type II endoleaks (T2ELs) are the most common cause of reintervention after endovascular aneurysm repair (EVAR). Although most resolve spontaneously, the long-term implications of T2ELs remain elusive. We aim to evaluate the impact of persistent and late T2ELs on clinical outcomes after EVAR. METHODS: This was a single-institution retrospective review of patients who underwent EVAR for degenerative infrarenal abdominal aortic aneurysm between January 2010 and June 2022 with no type I (T1EL) or III (T3EL) endoleak seen at EVAR completion. Patients were categorized based on T2EL status. Group 1 included patients with never detected or transient T2ELs (detected at EVAR completion but not after). Group 2 encompassed persistent T2ELs (seen at EVAR completion and again during follow-up) and late T2ELs (detected for the first time at any point during follow-up). Time-to-event analysis was conducted using a time-dependent approach to T2EL status. Primary outcomes included freedom from sac enlargement (SE), aneurysm-related reinterventions, and overall survival. RESULTS: A total of 803 patients met inclusion criteria. Group 1 included 418 patients (52%), of which 85% had no T2ELs and 15% had transient T2ELs. Group 2 had 385 patients; 23% had persistent T2ELs, and 77% developed a new T2EL. Patients in group 1 had a higher prevalence of smoking (88% vs 83%; P < .001), chronic obstructive pulmonary disease (33% vs 25%; P = .008), chronic kidney disease (13% vs 8%; P = .021), and a higher mean Society for Vascular Surgery score (7 vs 6 points; P = .049). No differences were found in aneurysm diameter or morphology. Mean follow-up was 5 years for the entire cohort. In Group 2, 58 patients (15%) underwent T2EL treatment, most commonly transarterial embolization. At 10 years after EVAR, Group 2 was associated with lower freedom from SE (P < .001) and abdominal aortic aneurysm-related reinterventions (P < .001) and comparable overall survival (P = .42). More T1ELs were detected during follow-up in Group 2 (6 [1%] vs 20 [5%]; P = .004), with 15 (75%) of these detected at a median of 3 years after the T2EL. No difference between groups was observed in explant (0.7% vs 2.1%; P = .130) or aneurysm rupture (0.5% vs 1.3%; P = .269) rates. CONCLUSIONS: One-half of patients treated with infrarenal EVAR developed persistent/late T2ELs, which are associated with a higher risk of SE and reinterventions. No difference in overall survival or aneurysm rupture risk was seen at 10 years, based on T2EL status or T2EL intervention. A conservative approach to T2ELs may be appropriate for most patients with absent T1ELs or T3ELs.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

Inhibiting CRF Projections from the Central Amygdala to Lateral Hypothalamus and Amygdala Deletion of CRF Alters Binge-Like Ethanol Drinking in a Sex-Dependent Manner.

Background: Binge alcohol drinking is a dangerous pattern of consumption that can contribute to the development of more severe alcohol use disorders (AUDs). Importantly, the rate and severity of AUDs has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in central CRF systems. Methods: In the present report we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice. Results: Using chemogenetic tools we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male, but not female, mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF type-1 receptor (CRF1R) in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF2R activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking blunted CRF mRNA in the CeA regardless of sex. Conclusions: These observations provide novel evidence that CRF+ CeA to LH neurocircuitry modulates binge-like ethanol intake in male, but not female mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.

Hybrid repair of tandem high-grade innominate and carotid artery stenosis in an asymptomatic male.

Tandem atherosclerotic lesions of the innominate artery (IA) and internal carotid artery (ICA) are challenging and represent an inherent risk of cerebrovascular accident. Treating asymptomatic patients is controversial; therefore, it is critical to minimize the risk of a cerebrovascular accident if repair is undertaken. An asymptomatic 78-year-old man with a chronically occluded left ICA and tandem stenoses of the IA and right ICA underwent a hybrid intervention with stenting of the IA lesion and right ICA endarterectomy. The intra- and postoperative course was successful, without any signs of neurological sequelae. Sixteen months later, the patient remained asymptomatic, with patent reconstructions.

Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.

Objective: To identify imaging subtypes of the cortico-basal syndrome (CBS) based solely on a data-driven assessment of MRI atrophy patterns, and investigate whether these subtypes provide information on the underlying pathology. Methods: We applied Subtype and Stage Inference (SuStaIn), a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 CBS cases (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and validated using follow-up MRI. We compared the clinical phenotypes of each subtype and investigated whether there were differences in associated pathology between the subtypes. Results: SuStaIn identified two subtypes with distinct sequences of atrophy progression; four-repeat-tauopathy confirmed cases were most commonly assigned to the Subcortical subtype (83% of CBS-PSP and 75% of CBS-CBD), while CBS-AD was most commonly assigned to the Fronto-parieto-occipital subtype (81% of CBS-AD). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. Interpretation: By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in CBS that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with CBS at baseline has important implications for screening on entry into clinical trials, as well as for tracking disease progression.

Accuracy and Usability of Smartphone-Based Distance Estimation Approaches for Visual Assistive Technology Development.

Goal: Distance information is highly requested in assistive smartphone Apps by people who are blind or low vision (PBLV). However, current techniques have not been evaluated systematically for accuracy and usability. Methods: We tested five smartphone-based distance-estimation approaches in the image center and periphery at 1-3 meters, including machine learning (CoreML), infrared grid distortion (IR_self), light detection and ranging (LiDAR_back), and augmented reality room-tracking on the front (ARKit_self) and back-facing cameras (ARKit_back). Results: For accuracy in the image center, all approaches had <±2.5 cm average error, except CoreML which had ±5.2-6.2 cm average error at 2-3 meters. In the periphery, all approaches were more inaccurate, with CoreML and IR_self having the highest average errors at ±41 cm and ±32 cm respectively. For usability, CoreML fared favorably with the lowest central processing unit usage, second lowest battery usage, highest field-of-view, and no specialized sensor requirements. Conclusions: We provide key information that helps design reliable smartphone-based visual assistive technologies to enhance the functionality of PBLV.

Influence of microclimate and forest management on bat species faced with global change.

Climate refugia, areas where climate is expected to remain relatively stable, can offer a near-term safe haven for species sensitive to warming temperatures and drought. Understanding the influence of temperature, moisture, and disturbance on sensitive species is critical during this time of rapid climate change. Coastal habitats can serve as important refugia. Many of these areas consist of working forestlands, and there is a growing recognition that conservation efforts worldwide must consider the habitat value of working lands, in addition to protected areas, to effectively manage large landscapes that support biodiversity. The sensitivity of forest bats to climate and habitat disturbance makes them a useful indicator taxon. We tested how microclimate and forest management influence habitat use for 13 species of insectivorous bats in a large climate refugium in a global biodiversity hotspot. We examined whether bat activity during the summer dry season is greater in forests where coastal fog provides moisture and more stable temperatures across both protected mature stands and those regularly logged. Acoustic monitoring was conducted at a landscape scale with 20 study sites, and generalized linear mixed models were used to examine the influence of habitat variables. Six species were positively associated with warmer nighttime temperature, and 5 species had a negative relationship with humidity or a positive relationship with climatic moisture deficit. Our results suggest that these mammals may have greater climate adaptive capacity than expected, and, for now, that habitat use may be more related to optimal foraging conditions than to avoidance of warming temperatures and drought. We also determined that 12 of the 13 regionally present bat species were regularly detected in commercial timberland stands. Because forest bats are highly mobile, forage over long distances, and frequently change roosts, the stewardship of working forests must be addressed to protect these species.

Influencia del microclima y el manejo forestal sobre especies de murciélagos ante el cambio global Resumen Los refugios climáticos, áreas en donde se espera que el clima permanezca relativamente estable, pueden ofrecer un santuario a corto plazo para las especies sensibles al aumento de temperaturas y la sequía. Es muy importante entender la influencia de la temperatura, la humedad y las perturbaciones sobre las especies sensibles durante estos tiempos de cambio climático repentino. Los hábitats costeros pueden funcionar como refugios importantes. Muchas de estas áreas consisten en bosques funcionales y cada vez hay más reconocimiento de que los esfuerzos mundiales de conservación deben considerar el valor del hábitat de los suelos funcionales, además de las áreas protegidas, para manejar de manera efectiva los extensos paisajes que mantienen a la biodiversidad. La sensibilidad de los murciélagos de los bosques ante las perturbaciones climáticas y de hábitat hace que sean un taxón indicador útil. Analizamos cómo los microclimas y el manejo forestal influyen sobre el uso de hábitat de 13 especies de murciélagos insectívoros en un refugio climático amplio dentro de un punto caliente de biodiversidad mundial. Examinamos si la actividad de los murciélagos durante la temporada seca de verano es mayor en los bosques en donde la niebla costera proporciona humedad y temperaturas más estables tanto en los árboles maduros como aquellos que son talados con regularidad. Realizamos el monitoreo acústico a escala de paisaje en 20 estudios de sitio y usamos modelos lineales mixtos generalizados para examinar la influencia de las variables del hábitat. Seis especies estuvieron asociadas positivamente con la temperatura nocturna más cálida y cinco especies tuvieron una relación negativa con la humedad o una relación positiva con el déficit climático de humedad. Nuestros resultados sugieren que estos mamíferos pueden tener una mayor capacidad de adaptación climática de lo que se pensaba y, por ahora, que el uso de hábitat puede estar más relacionado con las condiciones óptimas de forrajeo que con la evasión de las temperaturas elevadas y la sequía. También determinamos que 12 de las 13 especies con presencia regional fueron detectadas con regularidad en los puntos de tala comercial. Ya que los murciélagos del bosque tienden a moverse mucho, forrajear a lo largo de grandes distancias y con frecuencia cambiar de nido, debemos abordar la administración de los bosques funcionales para proteger a estas especies.

Association of mesenteric volvulus in police working dogs with and without a prior prophylactic laparoscopic gastropexy.

OBJECTIVE: To evaluate the association of mesenteric volvulus (MV) in New York Police Department police working dogs (PWDs) with and without a prior prophylactic laparoscopic gastropexy (PLG). ANIMALS: 370 PWDs (82 with and 288 without PLG). METHODS: Medical records and surgery and radiology reports were reviewed from 2012 to 2022. Signalment, pertinent history (medical and surgical), gastropexy status, temperament, and training type were recorded. Statistical analysis was used to identify the relationship between prophylactic gastropexy and MV within the patient population. RESULTS: 3 cases of mesenteric volvulus were noted in this patient population. Two (2.4%) of the 82 PWDs that had undergone prophylactic laparoscopic gastropexy developed MV, whereas 1 (0.3%) of the 288 PWDs that had not undergone a gastropexy procedure developed MV. Police working dogs with PLG were estimated to be at 7.2 times greater odds of MV (point estimate OR, 7.18; 95% CI, 0.642 to 80.143); however, the low incidence of MV in this population limited statistical power, and thus this effect did not achieve statistical significance. Evaluation of MV incidence in additional populations of working dogs will allow greater precision in the point estimate. CLINICAL RELEVANCE: Prophylactic gastropexy may be associated with an increased risk for MV. However, patients without prophylactic gastropexy are at risk for gastric dilatation and volvulus, which is more common than MV. Therefore, the authors continue to recommend prophylactic gastropexy to decrease the risk for gastric dilatation and volvulus.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.