A single risk assessment for the most common diseases of ageing, developed and validated on 10 cohort studies.

BACKGROUND: We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors. METHODS: Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. Disease-free participants at baseline were included, and 22 risk factors (sociodemographic, medical, lifestyle, laboratory biomarkers) were evaluated. Two risk tools (DemNCD and DemNCD-LR based on Fine and Gray sub-distribution and logistic regression [LR], respectively) were developed and validated. Predictive accuracies of these risk tools were assessed using Harrel's C-statistics and area under the curve (AUC) and 95% confidence interval (CI). Model calibration was conducted using Hosmer-Lemeshow goodness of fit test along calibration plots. RESULTS: Both the DemNCD and DemNCD-LR resulted in similar predictive accuracy for each outcome. The overall AUC (95% CI) for dementia, stroke, MI, and diabetes risk tool were 0·68 (0·65, 0·70), 0·58 (0·54, 0·61), 0·65 (0·61, 0·68), and 0·68 (0·64, 0·72), respectively, for males. For females, these figures were 0·65 (0·63, 0·67), 0·55 (0·52, 0·57), 0·65 (0·62, 0·68), and 0·61 (0·57, 0·65). CONCLUSIONS: The DemNCD is the first tool to predict both dementia and multiple cardio-metabolic diseases using comprehensive risk factors and provided similar predictive accuracy to existing risk tools. It has similar predictive accuracy as tools designed for single outcomes in this age-group. DemNCD has the potential to be used in community and clinical settings as it includes self-reported and routinely available clinical measures.

Maffucci Syndrome May Be a Heritable Thoracic Aortic Disease and a Cause of Aortic Dissection.

A woman with Maffucci syndrome (MS) presented post partum with type B aortic dissection leading to rupture of a thoracoabdominal aneurysm. Results of multiple-gene testing for heritable thoracic aortic disease were negative. Although conjectural, this patient's aortic disease may be related to MS, and surveillance for aortic disease in patients with MS may be appropriate.

Whole-genome sequencing resolves biochemical misidentification of Neisseria species from urogenital specimens.

Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) are human pathogens that sometimes occupy the same anatomical niche. Ng, the causative agent of gonorrhea, infects 87 million individuals annually worldwide and is an urgent threat due to increasing drug resistance. Ng is a pathogen of the urogenital tract and may infect the oropharyngeal or rectal site, often asymptomatically. Conversely, Nm is an opportunistic pathogen. While often a commensal in the oropharyngeal tract, it is also the leading cause of bacterial meningitis with 1.2 million cases globally, causing significant morbidity and mortality. Horizontal gene transfer (HGT) is likely to occur between Ng and Nm due to their shared anatomical niches and genetic similarity, which poses challenges for accurate detection and treatment. Routine surveillance through the Gonococcal Isolate Surveillance Project and Strengthening the U.S. Response to Resistant Gonorrhea detected six concerning urogenital Neisseria isolates with contradicting species identification in Milwaukee (MIL). While all six isolates were positive for Ng using nucleic acid amplification testing (NAAT) and matrix-assisted laser desorption/ionization time of flight identified the isolates as Ng, two biochemical tests, Gonochek-II and API NH, classified them as Nm. To address this discrepancy, we performed whole-genome sequencing (WGS) using Illumina MiSeq on all isolates and employed various bioinformatics tools. Species detection analysis using BMScan, which uses WGS data, identified all isolates as Ng. Furthermore, Kraken revealed over 98% of WGS reads mapped to the Ng genome and <1% to Nm. Recombination analysis identified putative HGT in all MIL isolates within the γ-glutamyl transpeptidase (ggt) gene, a key component in the biochemical tests used to differentiate between Nm and Ng. Further analysis identified Nm as the source of HGT event. Specifically, the active Nm ggt gene replaced the Ng pseudogenes, ggt1 and ggt2. Together, this study demonstrates that closely related Neisseria species sharing a niche underwent HGT, which led to the misidentification of species following biochemical testing. Importantly, NAAT accurately detected Ng. The misidentification highlights the importance of using WGS to continually evaluate diagnostic or bacterial identification tests.

Trauma and 'Whole' Body Computed Tomography: Role, Protocols, Appropriateness, and Evidence to Support its Use and When.

Imaging plays a crucial role in the immediate evaluation of the trauma patient, particularly using multi-detector computed tomography (CT), and especially in moderately to severely injured trauma patients. There are specific areas of relative consensus, while other aspects of whole-body computed tomography (WB-CT) use remain controversial and are subject to opinion/debate based on the current literature. Even a few hours of a delayed diagnosis may result in a detrimental outcome for the patient. One must utilize all the tools available to enhance the interpretation of images. It is also important to recognize imaging pitfalls and artifacts to avoid unnecessary intervention.

Snapshotting quantum dynamics at multiple time points.

Measurement-induced state disturbance is a major challenge in obtaining quantum statistics at multiple time points. We propose a method to extract dynamic information from a quantum system at intermediate time points, namely snapshotting quantum dynamics. To this end, we apply classical post-processing after performing the ancilla-assisted measurements to cancel out the impact of the measurements at each time point. Based on this, we reconstruct a multi-time quasi-probability distribution (QPD) that correctly recovers the probability distributions at the respective time points. Our approach can also be applied to simultaneously extract exponentially many correlation functions with various time-orderings. We provide a proof-of-principle experimental demonstration of the proposed protocol using a dual-species trapped-ion system by employing 171Yb+ and 138Ba+ ions as the system and the ancilla, respectively. Multi-time measurements are performed by repeated initialization and detection of the ancilla state without directly measuring the system state. The two- and three-time QPDs and correlation functions are reconstructed reliably from the experiment, negativity and complex values in the QPDs clearly indicate a contribution of the quantum coherence throughout dynamics.

Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase.

OBJECTIVE: Caloric restriction (CR) is known to enhance insulin sensitivity and reduce the risk of metabolic disorders; however, its molecular mechanisms are not fully understood. This study aims to elucidate specific proteins and pathways responsible for these benefits. METHODS: We examined adipose tissue from participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study, comparing proteomic profiles from individuals after 12 and 24 months of CR with baseline and an ad libitum group. Biochemical and cell-specific physiological approaches complemented these analyses. RESULTS: Our data revealed that CR upregulates prostacyclin synthase (PTGIS) in adipose tissue, an enzyme crucial for producing prostacyclin (PGI2). PGI2 improves the ability of insulin to stimulate the tether-containing UBX domain for GLUT4 (TUG) cleavage pathway, which is essential for glucose uptake regulation. Additionally, iloprost, a PGI2 analog, was shown to increase insulin receptor density on cell membranes, increasing glucose uptake in human adipocytes. CR also reduces carbonylation of GLUT4, a modification that is detrimental to GLUT4 function. CONCLUSIONS: CR enhances insulin sensitivity by promoting PTGIS expression and stimulating the TUG cleavage pathway, leading to increased GLUT4 translocation to the cell surface and decreased GLUT4 carbonylation. These findings shed light on the complex molecular mechanisms through which CR favorably impacts insulin sensitivity and metabolic health.

Joint self-supervised and supervised contrastive learning for multimodal MRI data: Towards predicting abnormal neurodevelopment.

The integration of different imaging modalities, such as structural, diffusion tensor, and functional magnetic resonance imaging, with deep learning models has yielded promising outcomes in discerning phenotypic characteristics and enhancing disease diagnosis. The development of such a technique hinges on the efficient fusion of heterogeneous multimodal features, which initially reside within distinct representation spaces. Naively fusing the multimodal features does not adequately capture the complementary information and could even produce redundancy. In this work, we present a novel joint self-supervised and supervised contrastive learning method to learn the robust latent feature representation from multimodal MRI data, allowing the projection of heterogeneous features into a shared common space, and thereby amalgamating both complementary and analogous information across various modalities and among similar subjects. We performed a comparative analysis between our proposed method and alternative deep multimodal learning approaches. Through extensive experiments on two independent datasets, the results demonstrated that our method is significantly superior to several other deep multimodal learning methods in predicting abnormal neurodevelopment. Our method has the capability to facilitate computer-aided diagnosis within clinical practice, harnessing the power of multimodal data. The source code of the proposed model is publicly accessible on GitHub: https://github.com/leonzyzy/Contrastive-Network.

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

In vivo Multi-perspective 3D + t Ultrasound Imaging and Motion Estimation of Abdominal Aortic Aneurysms.

Time-resolved three-dimensional ultrasound (3D + t US) is a promising imaging modality for monitoring abdominal aortic aneurysms (AAAs), providing their 3D geometry and motion. The lateral contrast of US is poor, a well-documented drawback which multi-perspective (MP) imaging could resolve. This study aims to show the feasibility of in vivo multi-perspective 3D + t ultrasound imaging of AAAs for improving the image contrast and displacement accuracy. To achieve this, single-perspective (SP) aortic ultrasound images from three different angles were spatiotemporally registered and fused, and the displacements were compounded. The fused MP had a significantly higher wall-lumen contrast than the SP images, for both patients and volunteers (P < .001). MP radial displacements patterns are smoother than SP patterns in 67% of volunteers and 92% of patients. The MP images from three angles have a decreased tracking error (P < .001 for all participants), and an improved SNRe compared to two out of three SP images (P < .05). This study has shown the added value of MP 3D + t US, improving both image contrast and displacement accuracy in AAA imaging. This is a step toward using multiple or large transducers in the clinic to capture the 3D geometry and strain more accurately, for patient-specific characterization of AAAs.

The Dunning‒Kruger effect in resident predicted and actual performance on the American Board of Emergency Medicine in-training examination.

Objectives: The Dunning-Kruger effect (DKE) is a cognitive bias wherein individuals who are unskilled overestimate their abilities, while those who are skilled tend to underestimate their capabilities. The purpose of this investigation is to determine if the DKE exists among American Board of Emergency Medicine (ABEM) in-training examination (ITE) participants. Methods: This is a prospective, cross-sectional survey of residents in Accreditation Council for Graduate Medical Education (ACGME)-accredited emergency medicine (EM) residency programs. All residents who took the 2022 ABEM ITE were eligible for inclusion. Residents from international programs, residents in combined training programs, and those who did not complete the voluntary post-ITE survey were excluded. Half of the residents taking the ITE were asked to predict their self-assessment of performance (percent correct), and the other half were asked to predict their performance relative to peers at the same level of training (quintile estimate). Pearson's correlation (r) was used for parametric interval data comparisons and a Spearman's coefficient (ρ) was determined for quintile-to-quintile comparisons. Results: A total of 7568 of 8918 (84.9%) residents completed their assigned survey question. A total of 3694 residents completed self-assessment (mean predicted percentage correct 67.4% and actual 74.6%), with a strong positive correlation (Pearson's r 0.58, p < 0.001). There was also a strong positive correlation (Spearman's ρ 0.53, p < 0.001) for the 3874 residents who predicted their performance compared to peers. Of these, 8.5% of residents in the first (lowest) quintile and 15.7% of residents in the fifth (highest) quintile correctly predicted their performance compared to peers. Conclusions: EM residents demonstrated accurate self-assessment of their performance on the ABEM ITE; however, the DKE was present when comparing their self-assessments to their peers. Lower-performing residents tended to overestimate their performance, with the most significant DKE observed among the lowest-performing residents. The highest-performing residents tended to underestimate their relative performance.

Using eDNA to Supplement Population Genetic Analyses for Cryptic Marine Species: Identifying Population Boundaries for Alaska Harbour Porpoises.

Isolation by distance and biogeographical boundaries define patterns of population genetic structure for harbour porpoise along the Pacific coast from California to British Columbia. Until recently, inadequate sample sizes in many regions constrained efforts to characterise population genetic structure throughout the coastal waters of Alaska. Here, tissue samples from beachcast strandings and fisheries bycatch were supplemented with targeted environmental DNA (eDNA) samples in key regions of Alaska coastal and inland waters. Using a geographically explicit, hierarchical approach, we examined the genetic structure of Alaska harbour porpoises, using both mitochondrial DNA (mtDNA) sequence data and multilocus SNP genotypes. Despite a lack of evidence of genetic differentiation from nuclear SNP loci, patterns of relatedness and genetic differentiation from mtDNA suggest natal philopatry at multiple geographic scales, with limited gene flow among sites possibly mediated by male dispersal. A priori clustering of sampled areas at an intermediate scale (eastern and western Bering Sea, Gulf of Alaska and Southeast Alaska) best explained the genetic variance (12.37%) among regions. In addition, mtDNA differentiation between the Gulf of Alaska and eastern Bering Sea, and among regions within the Gulf of Alaska, indicated significant genetic structuring of harbour porpoise populations in Southeast Alaska. The targeted collection of eDNA samples from strata within Southeast Alaska was key for elevating the statistical power of our mtDNA dataset, and findings indicate limited dispersal between neighbouring strata within coastal and inland waters. These results provide evidence supporting a population boundary within the currently recognised Southeast Alaska Stock. Together, these findings will prove useful for ongoing management efforts to reduce fisheries conflict and conserve genetic diversity in this iconic coastal species.

Gestational organophosphate esters (OPEs) and executive function in adolescence: The HOME Study.

BACKGROUND: Evidence from toxicological studies indicate organophosphate esters (OPEs) are neurotoxic, but few epidemiological studies investigated associations between gestational OPEs and executive function. OBJECTIVE: To examine the associations between gestational concentrations of OPE urinary metabolites and executive function at 12 years METHODS: We used data from 223 mother-adolescent dyads from the Health Outcomes of Measures of the Environment (HOME) Study. Women provided spot urine samples at 16 weeks gestation, 26 weeks gestation, and at delivery for quantification of bis(1,3-dichloro-2-propyl) phosphate, bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP). Executive function was assessed at age 12 years using the parent- and self-report Behavior Rating Inventory of Executive Function (BRIEF2). Covariate-adjusted associations between specific gravity-corrected OPEs and BRIEF2 scores were estimated using multiple informant models. Bayesian Kernel Machine Regression (BKMR) was used to assess the impact of all OPEs simultaneously. RESULTS: Parent- and self-report BRIEF2 indices and composite scores were weakly to moderately correlated (rs=0.32-0.41). A natural-log unit increase in BCEP at 26 weeks was associated with approximately a 1-point increase on the self-report Cognitive Regulation Index [CRI] (95% CI 0.4, 2.3), the Emotion Regulation Index [ERI] (95% CI 0.3, 2.2), and the Global Executive Composite [GEC] (95% CI 0.4, 2.2), indicating poorer performance. Higher DPHP at 16 weeks was associated with lower parent-report GEC score (ß=-1.1, 95% CI -2.3, -0.003). BKMR identified BCEP and DNBP at 26 weeks as important contributors to CRI and ERI, respectively. CONCLUSION: OPE metabolites during gestational development, particularly BCEP, may influence adolescent executive function. However, since the FDR p-values failed to reach statistical significance, additional studies would benefit from using larger cohorts.

Head-to-head comparison of 68 Ga-FAPI-46 PET/CT, 18F-FDG PET/CT, and contrast-enhanced CT for the detection of various tumors.

OBJECTIVE: FAPI-PET/CT exhibits high tumor uptake and low background accumulation, enabling high-sensitivity tumor detection. We compared the diagnostic performance of 68 Ga-FAPI-46 PET/CT plus contrast-enhanced CT (CE-CT), 18F-FDG PET/CT plus CE-CT, and standalone CE-CT in patients with various malignancies. METHODS: 232 patients underwent 68 Ga-FAPI-46 PET/CT,18F-FDG PET/CT, and CE-CT each within 4 weeks. Detection rates were assessed by a blinded reader, with ≥ 2 weeks between scans of the same patient to avoid recall bias. A sub-analysis of diagnostic performance was performed for 490 histopathologically validated lesions. Detection rates were compared using McNemar's test. RESULTS: Lesion-based detection rates in 68 Ga-FAPI-46 PET/CT plus CE-CT, 18F-FDG PET/CT plus CE-CT, and CE-CT alone were 91.2% (1540/1688), 82.5% (1393/1688) and 60.2% (1016/1688). The detection rates were significantly higher for 68 Ga-FAPI-46 PET/CT plus CE-CT than for 18F-FDG PET/CT plus CE-CT (p < 0.02 for primary lesions and p < 0.001 for total, abdominopelvic nodal, liver and other visceral lesions) and CE-CT (p < 0.0001 for total, primary, cervicothoracic nodal, abdominopelvic nodal, liver, other visceral, and bone lesions). In the sub-analysis, sensitivity, specificity, positive and negative predictive value, and accuracy were 61.3%, 96.7%, 81.4%, 91.4% and 90.0% for 68 Ga-FAPI-46 PET/CT plus CE-CT, 57.0%, 95.7%, 75.7%, 90.5% and 88.4% for 18F-FDG PET/CT plus CE-CT, and 51.6%, 97.2%, 81.4%, 89.6% and 88.6% for CECT, respectively. CONCLUSIONS: 68 Ga-FAPI-46 PET/CT plus CE-CT demonstrates a higher tumor detection rate than 18F-FDG PET/CT plus CE-CT and CE-CT in a diverse spectrum of malignancies, especially for primary, abdominopelvic nodal, liver, and other visceral lesions. Further studies on which entities draw particular benefit from 68 Ga-FAPI-46 PET/CT are warranted to aid appropriate diagnostic workup. TRIAL REGISTRATION: A total of N = 232 patients were analyzed. Of these, N = 50 patients were included in a prospective interventional trial (NCT05160051), and N = 175 in a prospective observational trial (NCT04571086) for correlation and clinical follow-up of PET findings; N = 7 patients were analyzed retrospectively.

Personal care product use and per- and polyfluoroalkyl substances in pregnant and lactating people in the Maternal-Infant Research on Environmental Chemicals study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous chemicals routinely detected in personal care products (PCPs). However, few studies have evaluated the impact of PCP use on PFAS concentrations in pregnant and lactating populations. OBJECTIVE: We investigated associations between PCP use and PFAS concentrations in prenatal plasma and human milk. METHODS: We leveraged the Maternal-Infant Research on Environmental Chemicals (MIREC) Study to evaluate the contribution of PCP use on PFAS concentrations in prenatal plasma (6 to 13 weeks' gestation; n = 1,940) and human-milk (2 to 10 weeks' postpartum; n = 664). Participants reported frequency of use across 8 PCP categories during the 1st and 3rd trimesters, 1 to 2 days postpartum, and 2 to 10 weeks' postpartum. We used adjusted linear regression models to quantify percent differences and corresponding 95 % confidence intervals. RESULTS: In 1st trimester pregnant people, we found higher use of nailcare products (≥once a week vs. never: perfluorooctanoic acid (PFOA): 21 % [9.7 %, 32 %]; perfluorooctane-sulfonic acid (PFOS): 11 % [0.3 %, 23 %]), fragrances (daily vs. never: PFOA: 14 % [7.8 %, 21 %]; PFOS: 7.8 % [1.3 %, 15 %]), makeup (daily vs. never: PFOA: 14 % [5.8 %, 23 %]), hair dyes (never vs. 1-2 times during pregnancy: PFOA: 8.3 % [2.4 %, 15 %]), and hair sprays or gels (daily vs. never: PFOA: 12 % [5.0 %, 19 %], PFOS: 7.1 % [0.2 %, 15 %]) were associated with higher plasma PFAS concentrations. Similar results were observed for 3rd trimester PCP use and 2 to 10 weeks' postpartum human-milk PFAS concentrations. In addition, we also found that people using colored-permanent dye 1 to 2 days postpartum had higher Sm-PFOS (18 % [2.7 %, 35 %]), PFOA (16 % [4.3 %, 29 %]), and perfluorononanoic acid (17 % [3.6 %, 33 %]) postpartum human-milk concentrations. CONCLUSIONS: Our results show that PCP use may be a modifiable source of PFAS exposure in pregnant and lactating populations. These results along with growing scientific evidence can help inform PFAS regulation and guide individual choices to reduce PFAS exposure.

Video-feedback intervention to promote positive parenting and sensitive discipline in early elementary education (VIPP-School): a randomized controlled trial.

The VIPP-SD (Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline) program has been shown to promote positive interactions between parents and children with behavior problems. This study evaluated an adapted version for teachers (VIPP-School) through a parallel-group randomized controlled trial involving 58 teacher-child dyads from kindergarten to second grade. Teacher-child dyads were randomly assigned to VIPP-School (n = 28) or an active control group (n = 30). Intention-to-treat analyses showed improvements in teacher sensitivity (d = 0.87) and supportive teacher classroom interactions (d = 0.53) in the VIPP-School condition compared to the control condition. VIPP-School had no significant effect on teachers' observed sensitive discipline (although changes were in the expected direction), nor on reported child externalizing behavior, overall relationship quality, school happiness or teacher self-efficacy. These findings show that the intervention, originally developed for families, could be effectively applied to early elementary education. The limited number of sessions increases the feasibility of VIPP-School.

Comparing efficiencies of population control methods for responding to introductions of transboundary animal diseases in wild pigs.

Introductions of transboundary animal diseases (TADs) into free-ranging wildlife can be difficult to control and devastating for domestic livestock trade. Combating a new TAD introduction in wildlife with an emergency response requires quickly limiting spread of the disease by intensely removing wild animals within a contiguous area. In the case of African swine fever virus (ASFv) in wild pigs (Sus scrofa), which has been spreading in many regions of the world, there is little information on the time- and cost-efficiency of methods for intensively and consistently culling wild pigs and recovering carcasses in an emergency response scenario. We compared the efficiencies of aerial operations, trapping, experimental toxic baiting, and ground shooting in northcentral Texas, USA during two months in 2023. Culling and recovering carcasses of wild pigs averaged a rate of 0.15 wild pigs/person hour and cost an average of $233.04/wild pig ($USD 2023) across all four methods. Aerial operations required the greatest initial investment but subsequently was the most time- and cost-efficient, costing an average of $7266 to reduce the population by a standard measure of 10 %, including recovering carcasses. Aerial operations required a ground crew of ∼7 people/helicopter to recover carcasses. Costs for reducing the population of wild pigs using trapping were similar, although took 13.5 times longer to accomplish. In cases where carcass recovery and disposal are needed (e.g., response to ASFv), a benefit of trapping was immediate carcass recovery. Toxic baiting was less efficient because both culling and carcass recovery required substantial time. We culled very few wild pigs with ground shooting in this landscape. Our results provide insight on the efficiencies of each removal method. Strategically combining removal methods may increase overall efficiency. Overall, our findings inform the preparation of resources, personnel needs, and deployment readiness for TAD responses involving wild pigs.

Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial.

Primary results (median follow-up, 10.7 months) from the pivotal EPCORE® NHL-1 study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrated deep, durable responses with epcoritamab, a CD3xCD20 bispecific antibody, when used as monotherapy. We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively. An estimated 64.2% of complete responders remained in CR at 24 months. Estimated 24-month PFS and OS rates among complete responders were 65.1% and 78.2%, respectively. Of 119 minimal residual disease (MRD)-evaluable patients, 45.4% had MRD negativity, which correlated with longer PFS and OS. CR rates were generally consistent across predefined subgroups: 36% prior chimeric antigen receptor (CAR) T-cell therapy, 32% primary refractory disease, and 37% International Prognostic Index ≥3. The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia (23.6%). These results underscore the long-term benefit of epcoritamab for treating R/R LBCL with deep responses across subgroups, including patients with hard-to-treat disease and expected poor prognosis (ClinicalTrials.gov Registration: NCT03625037).

Agricultural and Ecological Resources Safeguarded by the Prevention of Wild Pig Population Expansion.

Wild pigs (Sus scrofa) are one of the most destructive invasive species in the US, known for causing extensive damage to agricultural commodities, natural resources, and property, and for transmitting diseases to livestock. Following the establishment of the National Feral Swine Damage Management Program (NFSDMP) in 2014, the expansion of wild pig populations has been successfully slowed. This paper combines two modeling approaches across eight separate models to characterize the expansion of wild pig populations in the absence of intervention by the NFSDMP and forecasts the value of a subset of resources safeguarded from the threat of wild pigs. The results indicate that if wild pigs had continued spreading at pre-program levels, they would have spread extensively across the US, with significant geographic variation across modeling scenarios. Further, by averting the threat of wild pigs, a substantial amount of crops, land, property, and livestock was safeguarded by the NFSDMP. Cumulatively, between 2014 and 2021, wild pig populations were prevented from spreading to an average of 724 counties and an average of USD 40.2 billion in field crops, pasture, grasses, and hay was safeguarded. The results demonstrate that intervention by the NFSDMP has delivered significant ecological and economic benefits that were not previously known.

Taxonomic variation, plastic degradation, and antibiotic resistance traits of plastisphere communities in the maturation pond of a wastewater treatment plant.

Wastewater treatment facilities can filter out some plastics before they reach the open environment, yet microplastics often persist throughout these systems. As they age, microplastics in wastewater may both leach and sorb pollutants and fragment to provide an increased surface area for bacterial attachment and conjugation, possibly impacting antimicrobial resistance (AMR) traits. Despite this, little is known about the effects of persistent plastic pollution on microbial functioning. To address this knowledge gap, we deployed five different artificially weathered plastic types and a glass control into the final maturation pond of a municipal wastewater treatment plant in Otautahi-Christchurch, Aotearoa/New Zealand. We sampled the plastic-associated biofilms (plastisphere) at 2, 6, 26, and 52 weeks, along with the ambient pond water, at three different depths (20, 40, and 60 cm from the pond water surface). We investigated the changes in plastisphere microbial diversity and functional potential through metagenomic sequencing. Bacterial 16S ribosomal RNA genes composition did not vary among plastic types and glass controls (P = 0.997) but varied among sampling times [permutational multivariate analysis of variance (PERMANOVA), P = 0.001] and depths (PERMANOVA, P = 0.011). Overall, there was no polymer-substrate specificity evident in the total composition of genes (PERMANOVA, P = 0.67), but sampling time (PERMANOVA, P = 0.002) and depth were significant factors (PERMANOVA, P = 0.001). The plastisphere housed diverse AMR gene families, potentially influenced by biofilm-meditated conjugation. The plastisphere also harbored an increased abundance of genes associated with the biodegradation of nylon, or nylon-associated substances, including nylon oligomer-degrading enzymes and hydrolases.IMPORTANCEPlastic pollution is pervasive and ubiquitous. Occurrences of plastics causing entanglement or ingestion, the leaching of toxic additives and persistent organic pollutants from environmental plastics, and their consequences for marine macrofauna are widely reported. However, little is known about the effects of persistent plastic pollution on microbial functioning. Shotgun metagenomics sequencing provides us with the necessary tools to examine broad-scale community functioning to further investigate how plastics influence microbial communities. This study provides insight into the functional consequence of continued exposure to waste plastic by comparing the prokaryotic functional potential of biofilms on five types of plastic [linear low-density polyethylene (LLDPE), nylon-6, polyethylene terephthalate, polylactic acid, and oxygen-degradable LLDPE], glass, and ambient pond water over 12 months and at different depths (20, 40, and 60 cm) within a tertiary maturation pond of a municipal wastewater treatment plant.