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Tropical cyclones are an important cause of forest disturbance, and major storms caused severe structural damage and elevated tree mortality in coastal tropical forests. Model capabilities that can be used to understand post-hurricane forest recovery are still limited. We use a vegetation demography model, the Functionally Assembled Terrestrial Ecosystem Simulator, coupled with the Energy Exascale Earth System Model Land Model (ELM-FATES) to study the processes and the key factors regulating post-hurricane forest recovery. We implemented hurricane-induced forest damage, including defoliation, structural biomass reduction, and tree mortality, performed ensemble model simulations, and used random forest feature importance. For the simulation in the Luquillo Experimental Forest, Puerto Rico, we identified factors controlling the post-hurricane forest recovery, and quantified the sensitivity of key model parameters to the post-hurricane forest recovery. The results indicate a tendency for the Bisley forests to shift toward the light demanding plant functional type (PFT) when the pre-hurricane biomass between the light demanding and shade tolerant PFTs is nearly equal and forests experience hurricane disturbance with mortality >60% for both the two PFTs. Under more realistic conditions where the shade tolerant PFT is initially dominant, mortality >80% is required for a shift toward dominance of the light demanding PFT at Bisley. Hurricane mortality and background mortality are the two major factors regulating post-hurricane forest recovery in simulations. This research improves understanding of the ELM-FATES model behavior associated with hurricane disturbance and provides guidance for dynamic vegetation model development in representing hurricane induced forest damage with varied intensities.

PurposeTo report a large uveal melanoma with extra-scleral extension which underwent spontaneous infarction and its unique molecular signature profile.ObservationsAn 81-year-old female presented with a blind, painful eye. Intraocular pressure was 48 mm Hg. There was a large subconjunctival melanotic mass overlying a choroidal melanoma with anterior extension involving the ciliary body and the iridocorneal angle and iris. Ultrasonography confirmed a dome-shaped anterior cilio-choroidal mass with extra-scleral extension. The patient underwent enucleation and pathologic evaluation confirmed cilio-choroidal melanoma. The posterior half of the tumor involving the ciliary body and the extra-scleral component were spontaneously infarcted and were composed of large melanophages. Next-generation sequencing demonstrated a splice site mutation in PBRM1 and whole-genome doubling in addition to a GNAQ hotspot mutation, chromosome 3 loss and 8q gain.Conclusions and importanceThis case of a large, auto-infarcted uveal melanoma demonstrates a PBRM1 mutation and whole-genome doubling.

Abstract This study critically examines the use of geodetic strain rates for forecasting long-term earthquake rates in a slow-deforming region such as Italy, challenging the prevailing assumption of their temporal stationarity in interseismic stages for seismic hazard analyses. Typically, earthquake-rate models derived from geodesy assume stationary interseismic loading rates, with stress rates in the upper crust proportional to geodetic strain rates, leading to earthquake rates directly proportional to these strain rate tensors. However, our analysis unveils a pronounced correlation between the epicenters of earthquakes that occurred in the past 60–120 years and areas forecasted for higher future earthquake rates based on geodetic strain rates. This correlation appears weak and scattered in analyses of even older earthquakes. To corroborate our findings, we select the 2009 L’Aquila earthquake (mw = 6.3) to prove that its apparently marginal viscoelastic relaxation significantly alters the time series of adjacent benchmarks for the following ~ 30–60 years, explaining the high correlation between recent earthquakes and strain rate peaks. Our findings require a methodological shift in interpreting geodetic data for earthquake forecasting, emphasizing the two-component (plate-tectonics-driven stationary long-term deformation, and decadal transient viscoelastic relaxation after an earthquake) nature of crustal stress accumulation recorded in geodetic data. We underscore the potential of geodesy-derived forecasts to provide deeper insights into seismic hazards, stressing the importance of acknowledging the long-term temporal variability inherent in geodetic measurements.

In-hospital electrocardiographic (ECG) monitors are typically configured to alarm for premature ventricular complexes (PVCs) due to the potential association of PVCs with ventricular tachycardia (VT). However, no contemporary hospital-based studies have examined the association of PVCs with VT. Hence, the benefit of PVC monitoring in hospitalized patients is largely unknown. This secondary analysis used a large PVC alarm data set to determine whether PVCs identified during continuous ECG monitoring were associated with VT, in-hospital cardiac arrest (IHCA), and/or death in a cohort of adult intensive care unit patients. Six PVC types were examined (i.e., isolated, bigeminy, trigeminy, couplets, R-on-T, and run PVCs) and were compared between patients with and without VT, IHCA, and/or death. Of 445 patients, 48 (10.8%) had VT; 11 (2.5%) had IHCA; and 49 (11%) died. Isolated and run PVC counts were higher in the VT group (p = 0.03 both), but group differences were not seen for the other four PVC types. The regression models showed no significant associations between any of the six PVC types and VT or death, although confidence intervals were wide. Due to the small number of cases, we were unable to test for associations between PVCs and IHCA. Our findings suggest that we should question the clinical relevance of activating PVC alarms as a forewarning of VT, and more work should be done with larger sample sizes. A more precise characterization of clinically relevant PVCs that might be associated with VT is warranted.

BackgroundFalse ventricular tachycardia (VT) alarms are common during in-hospital electrocardiographic (ECG) monitoring. Prior research shows that the majority of false VT can be attributed to algorithm deficiencies.PurposeThe purpose of this study was: (1) to describe the creation of a VT database annotated by ECG experts and (2) to determine true vs. false VT using a new VT algorithm created by our group.MethodsThe VT algorithm was processed in 5320 consecutive ICU patients with 572,574 h of ECG and physiologic monitoring. A search algorithm identified potential VT, defined as: heart rate >100 beats/min, QRSs > 120 ms, and change in QRS morphology in >6 consecutive beats compared to the preceding native rhythm. Seven ECG channels, SpO2 , and arterial blood pressure waveforms were processed and loaded into a web-based annotation software program. Five PhD-prepared nurse scientists performed the annotations.ResultsOf the 5320 ICU patients, 858 (16.13%) had 22,325 VTs. After three levels of iterative annotations, a total of 11,970 (53.62%) were adjudicated as true, 6485 (29.05%) as false, and 3870 (17.33%) were unresolved. The unresolved VTs were concentrated in 17 patients (1.98%). Of the 3870 unresolved VTs, 85.7% (n = 3281) were confounded by ventricular paced rhythm, 10.8% (n = 414) by underlying BBB, and 3.5% (n = 133) had a combination of both.ConclusionsThe database described here represents the single largest human-annotated database to date. The database includes consecutive ICU patients, with true, false, and challenging VTs (unresolved) and could serve as a gold standard database to develop and test new VT algorithms.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and despite excellent local control, more than 50% of patients develop and die from metastatic disease. Loss of BAP1 nuclear staining, a surrogate marker of BAP1 mutation, and preferentially expressed antigen in melanoma (PRAME) messenger RNA overexpression, as assessed using qPCR, have previously been shown to correlate with increased metastasis rate in UM. In this study, we demonstrated that UM could be successfully risk-stratified using a combination of BAP1 and PRAME immunohistochemical (IHC) stains. We retrospectively reviewed 318 UM cases with sufficient tissue and performed BAP1 and PRAME IHC to stratify them as BAP1+/PRAME- (group 1, n = 135), BAP1+/PRAME+ (group 2, n = 43), BAP1-/PRAME- (group 3, n = 94), and BAP1-/PRAME+ (group 4, n = 46). Increasing the study risk group on the basis of loss of BAP1 expression and positive PRAME staining was associated with a higher rate of metastasis and disease-specific death and lower metastasis-free survival (MFS) and disease-specific survival (DSS). Among tumors with loss of BAP1 staining, PRAME positivity was associated with shorter MFS (P = .018) and showed a trend toward shorter DSS (P = .061). Among tumors with retained BAP1 staining, PRAME positivity was associated with shorter MFS and DSS (P = .001 and P = .021, respectively). In summary, a combination of BAP1 and PRAME IHC can be used for risk stratification of UMs.

Abstract Background Robust solutions to global, national, and regional burdens of communicable and non-communicable diseases, particularly related to diet, demand interdisciplinary or transdisciplinary collaborations to effectively inform risk analysis and policy decisions. Objective U.S. outbreak data for 2005–2020 from all transmission sources were analyzed for trends in the burden of infectious disease and foodborne outbreaks. Methods Outbreak data from 58 Microsoft Access® data tables were structured using systematic queries and pivot tables for analysis by transmission source, pathogen, and date. Trends were examined using graphical representations, smoothing splines, Spearman’s rho rank correlations, and non-parametric testing for trend. Hazard Identification was conducted based on the number and severity of illnesses. Results The evidence does not support increasing trends in the burden of infectious foodborne disease, though strongly increasing trends were observed for other transmission sources. Morbidity and mortality were dominated by person-to-person transmission; foodborne and other transmission sources accounted for small portions of the disease burden. Foods representing the greatest hazards associated with the four major foodborne bacterial diseases were identified. Fatal foodborne disease was dominated by fruits, vegetables, peanut butter, and pasteurized dairy. Conclusion The available evidence conflicts with assumptions of zero risk for pasteurized milk and increasing trends in the burden of illness for raw milk. For future evidence-based risk management, transdisciplinary risk analysis methodologies are essential to balance both communicable and non-communicable diseases and both food safety and food security, considering scientific, sustainable, economic, cultural, social, and political factors to support health and wellness for humans and ecosystems.

ObjectiveTo analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication.DesignRetrospective case-control study.SubjectsPatients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea.MethodsTargeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features.Main outcome measuresPresence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence.ResultsHotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized.ConclusionsIn this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.

Functionally bivalent non-covalent Fab dimers (Bi-Fabs) specific for the TCR/CD3 complex promote CD3 signaling on T cells. While comparing functional responses to stimulation with Bi-Fab, F(ab’)2 or mAb specific for the same CD3 epitope, we observed fratricide requiring anti-CD3 bridging of adjacent T cells. Surprisingly, anti-CD3 Bi-Fab ranked first in fratricide potency, followed by anti-CD3 F(ab’)2 and anti-CD3 mAb. Low resolution structural studies revealed anti-CD3 Bi-Fabs and F(ab’)2 adopt similar global shapes with CD3-binding sites oriented outward. However, under molecular dynamic simulations, anti-CD3 Bi-Fabs crosslinked CD3 more rigidly than F(ab’)2. Furthermore, molecular modelling of Bi-Fab and F(ab’)2 binding to CD3 predicted crosslinking of T cell antigen receptors located in opposing plasma membrane domains, a feature fitting with T cell fratricide observed. Thus, increasing rigidity of Fab-CD3 crosslinking between opposing effector-target pairs may result in stronger T cell effector function. These findings could guide improving clinical performance of bi-specific anti-CD3 drugs.

The aim of this study was to evaluate the impact of different pulp drying processes and extracting methods of avocado oil (Margarida), determined by quality indices, bioactive compounds and fatty acid profile. The avocado pulp was dried in air circulation oven at 40 °C and 60 °C, and in vacuum oven at 60 °C. The oil was extracted by mechanical press or by Soxhlet method. The acidity, peroxide value, iodine, refractive indices; phenolic compounds; carotenoids; chlorophyll; tocopherols; antioxidant activity; fatty acid profiles; ratio between hypocholesterolemic and hypercholesterolemic fatty acids (h/H); atherogenic and thrombogenic indices, besides avocado pulp characteristics were evaluated. The best oil quality was found for pulp dried at 60 °C under vacuum combined with Soxhlet extraction. The content of bioactive compounds was higher when the pulp was dried at 60 °C in an oven with air circulation combined with mechanical pressing. No significant effect was observed on the fatty acid profile. The atherogenic and thrombogenic indices showed low values and h/H ratio, within the desirable. The results showed advantage in drying the pulp at 60 °C. The oil evidenced being a good source of bioactive compounds, presenting an interesting fatty acid profile, h/h ratio, atherogenic and thrombogenic indices.

In this short essay, the author addresses challenges facing higher education in the COVID-19 era and how creativity may serve to transform its future.

BackgroundThe impact of depressive symptoms and anxiety on rural patients' decisions to seek care for worsening heart failure (HF) symptoms remains unknown. The purposes of this study were (1) to describe rural patients' reasons for delay in seeking care for HF, and (2) to determine whether depressive symptoms or anxiety was associated with patients' reasons for delay in seeking medical care for worsening symptoms.MethodsA total of 611 rural HF patients were included. Data on reasons for patient delay in seeking medical care (The Reasons for Delay Questionnaire), depressive symptoms (PHQ-9), and anxiety (BSI-ANX) were collected. Statistical analyses included chi-square and multiple regression.ResultsA total of 85.4% of patients reported at least 1 reason for delay. Patients with higher levels of depressive symptoms were more likely to cite embarrassment, problems with transportation, and financial concerns as a reason for delay. Patients with anxiety not only cited nonsymptom-related reasons but also reported symptom-related reasons for delay in seeking care (ie, symptoms seemed vague, not sure of symptoms, symptoms didn't seem to be serious enough, and symptoms were different from the last episode). In multiple regression, patients with greater depressive symptoms and anxiety had a greater number of reasons for delay in seeking care (P = .003 and P = .023, respectively).ConclusionsOur findings suggest that enhancement of patients' symptom appraisal abilities and improvement in psychological distress may result in a reduction in delay in seeking medical care for worsening symptoms in rural patients with HF.