Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.

RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial: Study rationale and design.

Out-of-hospital cardiac arrest (OHCA) occurs in nearly 350,000 people each year in the United States (US). Despite advances in pre and in-hospital care, OHCA survival remains low and is highly variable across systems and regions. The critical barrier to improving cardiac arrest outcomes is not a lack of knowledge about effective interventions, but rather the widespread lack of systems of care to deliver interventions known to be successful. The RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial is a 7-year pragmatic, cluster-randomized trial of 62 counties (57 clusters) in North Carolina using an established registry and is testing whether implementation of a customized set of strategically targeted community-based interventions improves survival to hospital discharge with good neurologic function in OHCA relative to control/standard care. The multifaceted intervention comprises rapid cardiac arrest recognition and systematic bystander CPR instructions by 9-1-1 telecommunicators, comprehensive community CPR training and enhanced early automated external defibrillator (AED) use prior to emergency medical systems (EMS) arrival. Approximately 20,000 patients are expected to be enrolled in the RACE CARS Trial over 4 years of the assessment period. The primary endpoint is survival to hospital discharge with good neurologic outcome defined as a cerebral performance category (CPC) of 1 or 2. Secondary outcomes include the rate of bystander CPR, defibrillation prior to arrival of EMS, and quality of life. We aim to identify successful community- and systems-based strategies to improve outcomes of OHCA using a cluster randomized-controlled trial design that aims to provide a high level of evidence for future application.

The human volatilome meets cancer diagnostics: past, present, and future of noninvasive applications.

BACKGROUND: Cancer is a significant public health problem, causing dozens of millions of deaths annually. New cancer screening programs are urgently needed for early cancer detection, as this approach can improve treatment outcomes and increase patient survival. The search for affordable, noninvasive, and highly accurate cancer detection methods revealed a valuable source of tumor-derived metabolites in the human metabolome through the exploration of volatile organic compounds (VOCs) in noninvasive biofluids. AIM OF REVIEW: This review discusses volatilomics-based approaches for cancer detection using noninvasive biomatrices (breath, saliva, skin secretions, urine, feces, and earwax). We presented the historical background, the latest approaches, and the required stages for clinical validation of volatilomics-based methods, which are still lacking in terms of making noninvasive methods available and widespread to the population. Furthermore, insights into the usefulness and challenges of volatilomics in clinical implementation steps for each biofluid are highlighted. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outline the methodologies for using noninvasive biomatrices with up-and-coming clinical applications in cancer diagnostics. Several challenges and advantages associated with the use of each biomatrix are discussed, aiming at encouraging the scientific community to strengthen efforts toward the necessary steps to speed up the clinical translation of volatile-based cancer detection methods, as well as discussing in favor of (i) hybrid applications (i.e., using more than one biomatrix) to describe metabolite modulations that can be "cancer volatile fingerprints" and (ii) in multi-omics approaches integrating genomics, transcriptomics, and proteomics into the volatilomic data, which might be a breakthrough for diagnostic purposes, onco-pathway assessment, and biomarker validations.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Does Single Dose Epinephrine Improve Outcomes for Patients with Out-of-Hospital Cardiac Arrest and Bystander CPR or a Shockable Rhythm?

BACKGROUND: A single dose epinephrine protocol (SDEP) for out-of-hospital cardiac arrest (OHCA) achieves similar survival to hospital discharge (SHD) rates as a multidose epinephrine protocol (MDEP). However, it is unknown if a SDEP improves SHD rates among patients with a shockable rhythm or those receiving bystander cardiopulmonary resuscitation (CPR). METHODS: This pre-post study, spanning 11/01/2016-10/29/2019 at 5 North Carolina EMS systems, compared pre-implementation MDEP and post-implementation SDEP in patients ≥18 years old with non-traumatic OHCA. Data on initial rhythm type, performance of bystander CPR, and the primary outcome of SHD were sourced from the Cardiac Arrest Registry to Enhance Survival. We compared SDEP vs MDEP performance in each rhythm (shockable and non-shockable) and CPR (bystander CPR or no bystander CPR) subgroup using Generalized Estimating Equations to account for clustering among EMS systems and to adjust for age, sex, race, witnessed arrest, arrest location, AED availability, EMS response interval, and presence of a shockable rhythm or receiving bystander CPR. The interaction of SDEP implementation with rhythm type and bystander CPR was evaluated. RESULTS: Of 1690 patients accrued (899 MDEP, 791 SDEP), 19.2% (324/1690) had shockable rhythms and 38.9% (658/1690) received bystander CPR. After adjusting for confounders, SHD was increased after SDEP implementation among patients with bystander CPR (aOR 1.61, 95%CI 1.03-2.53). However, SHD was similar in the SDEP cohort vs MDEP cohort among patients without bystander CPR (aOR 0.81, 95%CI 0.60-1.09), with a shockable rhythm (aOR 0.96, 95%CI 0.48-1.91), and with a non-shockable rhythm (aOR 1.26, 95%CI 0.89-1.77). In the adjusted model, the interaction between SDEP implementation and bystander CPR was significant for SHD (p = 0.002). CONCLUSION: Adjusting for confounders, the SDEP increased SHD in patients who received bystander CPR and there was a significant interaction between SDEP and bystander CPR. Single dose epinephrine protocol and MDEP had similar SHD rates regardless of rhythm type.

Public access defibrillator locations and details in Forsyth County, North Carolina: Results of a telephone survey canvas of large businesses to facilitate out-of-hospital cardiac arrest treatment.

BACKGROUND: Limited data are available on locations of public access defibrillation programs across communities in the United States, despite their widespread presence. Our goal was to determine publicly available AED locations of large businesses in a mixed urban-rural county. We then compared our survey results to a NC state-mandated AED registry and the county's emergency medical dispatch center AED registry. METHODS: We conducted structured phone surveys of all large businesses (>19 employees) and select small businesses (healthcare, government, childcare, educational, and religious organizations with 1-19 employees) in Forsyth County, NC (n = 1702) to determine AED ownership and location. In addition, AED lists were elicited from multi-building organizations (e.g., health systems, universities, and local government), the NC Office of Emergency Medical Services (OEMS), and the Forsyth County emergency medical dispatch center. RESULTS: Our survey yielded a response rate of 79.1 % and identified 411 businesses with ≥ 1 AEDs. An additional 162 AED locations were contained in AED lists from multi-building organizations and registries. In total, our canvas identified 963 AEDs at 573 unique locations. The majority of AEDs (65.1 % [627/963]) were not previously registered in the NC OEMS AED registry. Few identified AEDs (11.8 % [114/963]) were listed in the county emergency medical dispatch center registry.

A new active packaging system based on chickpea-based edible coatings added with microcapsules of Cosmos sulphureus Cav. flower extract.

BACKGROUND: The Cosmos sulphureus Cav. plant is studied for its high polyphenolic content with antioxidant properties. Its flowers, rich in phenolic acids, flavonoids, and tannins, hold promise as antioxidants in food preservation. The inclusion of these compounds in chickpea-based coatings with a previously studied preservative effect would be an excellent option as a food preservation method and microencapsulation addresses challenges like dispersion and degradation of polyphenols in the coating. The objective of this research was to evaluate the in vitro antioxidant activity of Cosmos sulphureus leaves, seed, and flower extracts and explore the protective effects of chickpea-based coatings containing microcapsules of flower polyphenolic extract on the chemical quality of stored roasted sunflower seeds during storage. RESULTS: The ethanolic leaf extract exhibited the highest antiradical activity, followed by the aqueous flower extract. After a storage period of 15 days, at 40 °C, the chickpea-based coatings effectively delayed lipid oxidation in the roasted sunflowers seeds, and the inclusion of polyphenolic microcapsules with 0.01% extract (SMC 0.01%) in the coating significantly improved the protective effect. By day 15 of storage, SMC 0.01% showed comparable peroxide value, conjugated dienes, and linoleic acid content to samples containing the synthetic antioxidant BHT (butylated hydroxytoluene). Samples that only contained chickpea-based coating and coating with polyphenolic microcapsules with 0.005% extract exhibited significantly greater reduction in fatty acid content compared to the 0.01% SMC treatment. CONCLUSION: The chickpea-based coating with polyphenolic microcapsules demonstrated antioxidant activity akin to synthetic BHT, offering a promising biopackaging solution for lipid-rich foods like roasted sunflower seeds. © 2024 Society of Chemical Industry.

Soymilk stability increase using polyphenols microcapsules.

Functional beverages have aroused a great interest to the food industry. Among the functional ingredients, there is a growing demand for antioxidant incorporation into foods, which implies a challenge to preserve their bioactivity. The health benefits provided by soymilk can be improved by the addition with microcapsules of polyphenols from peanut skin and this procedure is an alternative to protect these natural and bioactive compounds from environmental factors. The aim of this work was to determine the chemical, antioxidant, microbiological and sensory changes during storage of the product. Soymilk samples were prepared without any addition (C); with peanut skin extract (BEA); and with microcapsules with polyphenols (MCBEA) and stored at 4 °C for 30 days. Results showed that the addition of polyphenols (free or microencapsulated) improved the chemical, microbiological and sensory stability of soymilk. The BEA and MCBEA had lower values of hydroperoxides, hexanal, bacterial growth, oxidised flavour, and sweet taste than C. The BEA exhibited higher phenol content (819.72 mg gallic acid equivalents/L), antioxidant activity (64.66% DPPH inhibition) and colour intensity than MCBEA. The study suggested that polyphenol microencapsulation is a procedure that can protect these sensitive compounds and control their release into this food matrix.

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

Synthetic dyes: A mass spectrometry approach and applications.

Synthetic dyes are found in a wide variety of applications today, including but not limited to textiles, foods, and medicine. The analysis of these molecules is pertinent to several fields such as forensics, environmental monitoring, and quality control, all of which require the sensitivity and selectivity of analysis provided by mass spectrometry (MS). Recently, there has been an increase in the implementation of MS evaluation of synthetic dyes by various methods, with the majority of research thus far falling under electrospray ionization and moving toward direct ionization methods. This review covers an overview of the chemistry of synthetic dyes needed for the understanding of MS sample preparation and spectral results, current fields of application, ionization methods, and fragmentation trends and works that have been reported in recent years.

One and Done Epinephrine in Out-of-Hospital Cardiac Arrest? Outcomes in a Multiagency United States Study.

BACKGROUND: Cardiac arrest guidelines recommend epinephrine every 3-5 minutes during cardiac arrest resuscitation. However, it is unclear if multiple epinephrine doses are associated with improved outcomes. The objective of this study was to determine if a single-dose epinephrine protocol was associated with improved survival compared to traditional multidose protocols. METHODS: We conducted a pre-post study across five North Carolina EMS agencies from 11/1/2016 to 10/29/2019. Patients ≥18 years old with attempted resuscitation for non-traumatic prehospital cardiac arrest were included. Data were collected 1 year before and after implementation of the single-dose epinephrine protocol. Prior to implementation, all agencies used a multidose epinephrine protocol. The Cardiac Arrest Registry to Enhance Survival (CARES) was used to obtain patient outcomes. Study outcomes were survival to hospital discharge (primary) and return of spontaneous circulation (ROSC). Analysis was by intention to treat. Outcomes were compared pre- vs. post-implementation using generalized estimating equations to account for clustering within EMS agencies. Adjusted analyses included age, sex, race, shockable vs. non-shockable rhythm, witnessed arrest, automatic external defibrillator availability, EMS response interval, and bystander cardiopulmonary resuscitation. RESULTS: During the study period there were 1,690 encounters (899 pre- and 791 post-implementation). The population was 74.7% white, 61.1% male, and had a median age of 65 (IQR 53-76) years. Survival to hospital discharge was similar pre- vs. post-implementation [13.6% (122/899) vs. 15.4% (122/791); OR 1.19, 95%CI 0.89-1.59]. However, ROSC was more common post-implementation [42.3% (380/899) vs. 32.5% (257/791); OR 0.66, 95%CI 0.54-0.81]. After adjusting for covariates, the single-dose protocol was associated with similar survival to discharge rates (aOR 0.88, 95%CI 0.77-1.29), but with decreased ROSC rates (aOR 0.58, 95%CI 0.47-0.72). CONCLUSION: A prehospital single-dose epinephrine protocol was associated with similar survival to hospital discharge, but decreased ROSC rates compared to the traditional multidose epinephrine protocol.

Performance of Prehospital Use of Chest Pain Risk Stratification Tools: The RESCUE Study.

BACKGROUND: Emergency medical services (EMS) assesses millions of patients with chest pain each year. However, tools validated to risk stratify patients for acute coronary syndrome (ACS) and pulmonary embolism (PE) have not been translated to the prehospital setting. The objective of this study is to assess the prehospital performance of risk stratification scores for 30-day major adverse cardiac events (MACE) and PE. METHODS: A prospective observational cohort study of patients ≥21 years of age with acute chest pain who were transported by EMS in two North Carolina (NC) counties was conducted from 18 April 2018-2 January 2019. In this convenience sample, paramedics completed HEAR (history, electrocardiogram, age, risk factor), ED Assessment of Chest Pain Score (EDACS), Revised Geneva Score (RGS), and pulmonary embolism rule-out criteria (PERC) assessments on each patient. MACE (all-cause death, myocardial infarction, and revascularization) and PE at 30 days were determined by hospital records and NC Death Index. The positive (+LR) and negative likelihood ratios (-LR) of the risk scores for 30-day MACE and PE were calculated. RESULTS: During the study period, 82.1% (687/837) patients had all four risk score assessments. The cohort was 51.1% (351/687) female, 49.5% (340/687) African American, and had a mean age of 55.0 years (SD 16.0). At 30 days, MACE occurred in 7.4% (51/687), PE occurred in 0.9% (6/687), and the combined outcome occurred in 8.2% (56/687). The HEAR score had a - LR of 0.46 (95% CI 0.27-0.78) and + LR of 1.48 (95% CI 1.26-1.74) for 30-day MACE. EDACS had a - LR of 0.61 (95% CI 0.46-0.81) and + LR of 2.53 (95% CI 1.86-3.46) for 30-day MACE. The PERC score had a - LR of 0 (95% CI 0.0-1.4) and a + LR of 1.38 (95% CI 1.32-1.45) for 30-day PE. The RGS score had a - LR of 0 (95% CI 0.0-0.65) and a + LR of 2.36 (95% CI 2.16-2.57) for 30-day PE. The combination of a low-risk HEAR score and negative PERC evaluation had a - LR of 0.25 (95% CI 0.08-0.76) and a + LR of 1.21 (95% CI 1.21-1.30) for 30-day MACE or PE. CONCLUSION: The combination of a paramedic-obtained HEAR score and PERC evaluation performed best to exclude 30-day MACE and PE but was not sufficient for directing prehospital decision making.

Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis.

BACKGROUND: Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic. METHODS: Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low. RESULTS: Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07-1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96-1.14; moderate-certainty evidence). CONCLUSIONS: Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.

Fusion Object Detection and Action Recognition to Predict Violent Action.

In the context of Shared Autonomous Vehicles, the need to monitor the environment inside the car will be crucial. This article focuses on the application of deep learning algorithms to present a fusion monitoring solution which was three different algorithms: a violent action detection system, which recognizes violent behaviors between passengers, a violent object detection system, and a lost items detection system. Public datasets were used for object detection algorithms (COCO and TAO) to train state-of-the-art algorithms such as YOLOv5. For violent action detection, the MoLa InCar dataset was used to train on state-of-the-art algorithms such as I3D, R(2+1)D, SlowFast, TSN, and TSM. Finally, an embedded automotive solution was used to demonstrate that both methods are running in real-time.

Explainable deep drug-target representations for binding affinity prediction.

BACKGROUND: Several computational advances have been achieved in the drug discovery field, promoting the identification of novel drug-target interactions and new leads. However, most of these methodologies have been overlooking the importance of providing explanations to the decision-making process of deep learning architectures. In this research study, we explore the reliability of convolutional neural networks (CNNs) at identifying relevant regions for binding, specifically binding sites and motifs, and the significance of the deep representations extracted by providing explanations to the model's decisions based on the identification of the input regions that contributed the most to the prediction. We make use of an end-to-end deep learning architecture to predict binding affinity, where CNNs are exploited in their capacity to automatically identify and extract discriminating deep representations from 1D sequential and structural data. RESULTS: The results demonstrate the effectiveness of the deep representations extracted from CNNs in the prediction of drug-target interactions. CNNs were found to identify and extract features from regions relevant for the interaction, where the weight associated with these spots was in the range of those with the highest positive influence given by the CNNs in the prediction. The end-to-end deep learning model achieved the highest performance both in the prediction of the binding affinity and on the ability to correctly distinguish the interaction strength rank order when compared to baseline approaches. CONCLUSIONS: This research study validates the potential applicability of an end-to-end deep learning architecture in the context of drug discovery beyond the confined space of proteins and ligands with determined 3D structure. Furthermore, it shows the reliability of the deep representations extracted from the CNNs by providing explainability to the decision-making process.

A mechanism of inheritance of acquired traits in animals.

Observational and experimental evidence for the inheritance of acquired traits in animals is slowly, but steadily accumulating. The onset and transmission of acquired traits implies the acquisition and transmission from parents to progeny of new information, which is different from the genetic information contained in DNA. The new non-genetic information most commonly is passed on from parents to the offspring via gamete(s), but how it is precisely transmitted to the successive generations is still unknown. Based on adequate empirical evidence presented herein, a hypothesis is proposed of the inheritance of acquired traits in animals and the flow of the relevant parental information to the offspring.

A cerumenolomic approach to bovine trypanosomosis diagnosis.

INTRODUCTION: Trypanosomiasis caused by Trypanosoma vivax (T. vivax, subgenus Duttonella) is a burden disease in bovines that induces losses of billions of dollars in livestock activity worldwide. To control the disease, the first step is identifying the infected animals at early stages. However, convention tools for animal infection detection by T. vivax present some challenges, facilitating the spread of the pathogenesis. OBJECTIVES: This work aims to develop a new procedure to identify infected bovines by T. vivax using cerumen (earwax) in a volatilomic approach, here named cerumenolomic, which is performed in an easy, quick, accurate, and non-invasive manner. METHODS: Seventy-eight earwax samples from Brazilian Curraleiro Pé-Duro calves were collected in a longitudinal study protocol during health and inoculated stages. The samples were analyzed using Headspace/Gas Chromatography-Mass Spectrometry followed by multivariate analysis approaches. RESULTS: The cerumen analyses lead to the identification of a broad spectrum of volatile organic metabolites (VOMs), of which 20 VOMs can discriminate between healthy and infected calves (AUC = 0.991, sensitivity = 0.967, specificity = 1.000). Furthermore, 13 VOMs can indicate a pattern of discrimination between the acute and chronic phases of the T. vivax infection in the animals (AUC = 0.989, sensitivity = 0.944, specificity = 1.000). CONCLUSION: The cerumen volatile metabolites present alterations in their occurrence during the T.vivax infection, which may lead to identifying the infection in the first weeks of inoculation and discriminating between the acute and chronic phases of the illness. These results may be a breakthrough to avoid the T. vivax outbreak and provide a faster clinical approach to the animal.

MiniBooNE and MicroBooNE Combined Fit to a 3+1 Sterile Neutrino Scenario.

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

Characteristics and risk factors for thrombosis in POEMS syndrome: A retrospective evaluation of 230 patients.

Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS-associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS-associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of arterial events. There were differences in baseline features between the thrombosis group and the no thrombosis group, and these were driven by patients with arterial thrombosis. Risk factors for arterial thrombosis included thrombocytosis, elevated hemoglobin/hematocrit, extravascular volume overload, and splenomegaly. Hyperprolactinemia appeared to be a risk factor for venous thrombosis. The risk of thrombosis was most striking among men with elevated hemoglobin (32% vs. 5%, p < .001) and hematocrit (42% vs. 5%, p < .001) compared to men without. Most thromboses occurred prior to POEMS directed therapy, and most that occurred during therapy happened within 3 months of diagnosis. Twenty-one percent of patients with thrombosis had recurrence. In recognition of high overall rates of thrombosis in this population, all patients with POEMS syndrome should receive prophylactic antiplatelet therapy, and clinicians should consider anticoagulation in patients with risk factors for POEMS-associated thrombosis.

Innovative subtractive production of a digital removable complete denture from start to finish: a JPD Digital video presentation.

This JPD Digital video presentation presents the clinical treatment from start to finish in which a dual-shaded bi-coloured monolithic disk was used for the fabrication of an immediate digital complete denture followed by the delivery of a definitive digital complete denture. The treatment plan included extraction of the remaining maxillary and mandibular teeth followed by an esthetic evaluation with digital smile design. The digital definitive complete dentures were milled from a monolithic dual-shaded disk.