Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively ...investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity.
We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations.
During the period under review (1997–2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%.
In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity.
Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity.
•Racial disparities in endometrial cancer between white American and African American continue to widen•Three decades of current research has not lead to the elimination of this disparity•There is a complex intermingling of causation variables negatively affecting survival disparity•Race alone as a social construct is not the cause of this disparity•No biological markers have been identified that are clinically actionable for therapy or explain this disparity
The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, ...including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.
The National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is the first of its kind megajoule-class laser facility with 192 beams capable of delivering over 1.8 MJ and 500TW of ...351 nm light for high accuracy laser-matter interaction experiments. It has been commissioned and operated since 2009 to support a wide range of missions including the study of inertial confinement fusion, high energy density physics, material science, and laboratory astrophysics. In the first section of this paper we discuss the current status of laser performance obtained during the 408 target experiments completed in 2017. The performance spanned a wide range of laser energies, powers and pulse durations as requested for these target experiments. A special emphasis is given on energy delivery and cone power accuracy in the UV, as these are key parameters for successful experiments. In the second section of the paper, the results obtained during the 2017 performance quad campaign are briefly described. During this campaign a series of laser-only shots were taken to perform tests at elevated energies on a single NIF quad. These tests were designed to assess laser performance limits and operational costs against predictive models. This campaign culminated with the delivery of ~54 kJ of UV on a single quad of NIF, and 14 kJ on a single beam aperture, which are both to our knowledge the largest energies achieved to date for a neodymium-glass, frequency tripled architecture.
Abstract
Chute (CS) and exit (ES) scores are common subjective methods used to evaluate temperament in cattle production systems. A pen test, which allows behavior to be observed in a non-restrained ...setting, may also be an effective method to evaluate temperament by allowing more variation among animals to be expressed. The merit of pen scores in assisting producers in evaluating temperament is equivocal. The objectives of this study were to validate the usefulness of a pen score in delineating temperamental cattle and to determine whether these behavioral scores change under repeated and routine management. Over 3 consecutive years, a factorial design of two measurement protocols (frequent F, infrequent IN) and three recording periods was used. The F measurements were collected over 3 consecutive days and IN measurements only on day 1 within a recording period. Each year, 20 mostly Angus commercial Bos taurus heifers were randomly assigned to each protocol. Behavior was measured using a CS, ES, and exit velocity. Body temperature and heart rate also were recorded. A fecal and blood sample were collected and analyzed for levels of various metabolites including glucose concentration and serum cortisol. Following routine handling, each heifers’ response to 30 s of exposure to a human stressor was recorded both individually and in groups of four. An individual (IPS) and group (GPS) pen scores were assigned from 1 (docile) to 6 (aggressive). For all heifers, protocol, event, and their interaction, were compared on the first day of an event. For F heifers, event and day within event were instead used. Body weight was included as a covariate, with sire and year fitted as random effects. Reliability of IPS and GPS were determined using a kappa (K) coefficient. Both IPS and GPS were reliably assigned (K = 0.64 and 0.44 for IPS and GPS, respectively) and positively correlated with body temperature, heart rate, glucose, and serum cortisol (r = 0.28 to 0.37). Furthermore, F heifers acclimated to repeated handling in an individual pen setting (P < 0.05) while acclimation to handling within groups was not evident (P > 0.14). IPS provides a reliable evaluation of temperament in a non-restrained setting that is indicative of an animal’s response to stress and may be useful when attempting to make phenotypic selection decisions. However, temperamental heifers became calmer with repeated gentle handling.
Lay Summary
Chute and exit scores are common subjective methods used to evaluate temperament in cattle production systems. A pen test, which allows behavior to be observed in a non-restrained setting, may also be an effective method to evaluate temperament by allowing more variation among animals to be expressed. However, the merit of pen scores in assisting producers in evaluating temperament has yet to be discerned. Therefore, the objectives of this study were to validate the usefulness of pen scores in delineating temperamental cattle and to determine whether these behavioral scores change under repeated and routine management. Pen scores collected on heifers either individually or as a group could be assigned reliably and were indicative of an animal’s response to stress during normal handling practices. Temperamental heifers, when handled more frequently, acclimated to repeated handling in an individual pen setting but not in a group. Therefore, regardless of method, when cattle are excitable during their first handling experience, more than one observation of temperament may be beneficial before assessing temperament.
Pen scores collected on heifers either individually or as a group can be reliably assigned and are indicative of an animal’s response to stress during normal handling practices.
We present the first results from an experimental campaign to measure the atomic ablator-gas mix in the deceleration phase of gas-filled capsule implosions on the National Ignition Facility. Plastic ...capsules containing CD layers were filled with tritium gas; as the reactants are initially separated, DT fusion yield provides a direct measure of the atomic mix of ablator into the hot spot gas. Capsules were imploded with x rays generated in hohlraums with peak radiation temperatures of ∼294 eV. While the TT fusion reaction probes conditions in the central part (core) of the implosion hot spot, the DT reaction probes a mixed region on the outer part of the hot spot near the ablator-hot-spot interface. Experimental data were used to develop and validate the atomic-mix model used in two-dimensional simulations.
Therapeutic hypothermia (TH) improves survival and confers neuroprotection in out-of-hospital cardiac arrest (OHCA), but TH is underutilized, and regional systems of care for OHCA that include TH are ...needed.
The Cool It protocol has established TH as the standard of care for OHCA across a regional network of hospitals transferring patients to a central TH-capable hospital. Between February 2006 and August 2009, 140 OHCA patients who remained unresponsive after return of spontaneous circulation were cooled and rewarmed with the use of an automated, noninvasive cooling device. Three quarters of the patients (n=107) were transferred to the TH-capable hospital from referring network hospitals. Positive neurological outcome was defined as Cerebral Performance Category 1 or 2 at discharge. Patients with non-ventricular fibrillation arrest or cardiogenic shock were included, and patients with concurrent ST-segment elevation myocardial infarction (n=68) received cardiac intervention and cooling simultaneously. Overall survival to hospital discharge was 56%, and 92% of survivors were discharged with a positive neurological outcome. Survival was similar in transferred and nontransferred patients. Non-ventricular fibrillation arrest and presence of cardiogenic shock were associated strongly with mortality, but survivors with these event characteristics had high rates of positive neurological recovery (100% and 89%, respectively). A 20% increase in the risk of death (95% confidence interval, 4% to 39%) was observed for every hour of delay to initiation of cooling.
A comprehensive TH protocol can be integrated into a regional ST-segment elevation myocardial infarction network and achieves broad dispersion of this essential therapy for OHCA.
In biomedical applications, nanomaterial-based delivery vehicles, such as lipid nanoparticles, have emerged as promising instruments for improving the solubility, stability, and encapsulation of ...various payloads. This article provides a formal review focusing on the reactogenicity of empty lipid nanoparticles used as delivery vehicles, specifically emphasizing their application in mRNA-based therapies. Reactogenicity refers to the adverse immune responses triggered by xenobiotics, including administered lipid nanoparticles, which can lead to undesirable therapeutic outcomes. The key components of lipid nanoparticles, which include ionizable lipids and PEG-lipids, have been identified as significant contributors to their reactogenicity. Therefore, understanding the relationship between lipid nanoparticles, their structural constituents, cytokine production, and resultant reactogenic outcomes is essential to ensure the safe and effective application of lipid nanoparticles in mRNA-based therapies. Although efforts have been made to minimize these adverse reactions, further research and standardization are imperative. By closely monitoring cytokine profiles and assessing reactogenic manifestations through preclinical and clinical studies, researchers can gain valuable insights into the reactogenic effects of lipid nanoparticles and develop strategies to mitigate undesirable reactions. This comprehensive review underscores the importance of investigating lipid nanoparticle reactogenicity and its implications for the development of mRNA–lipid nanoparticle therapeutics in various applications beyond vaccine development.
Ignition implosions on the National Ignition Facility J. D. Lindl et al., Phys. Plasmas 11, 339 (2004) are underway with the goal of compressing deuterium-tritium fuel to a sufficiently high areal ...density (ρR) to sustain a self-propagating burn wave required for fusion power gain greater than unity. These implosions are driven with a very carefully tailored sequence of four shock waves that must be timed to very high precision to keep the fuel entropy and adiabat low and ρR high. The first series of precision tuning experiments on the National Ignition Facility, which use optical diagnostics to directly measure the strength and timing of all four shocks inside a hohlraum-driven, cryogenic liquid-deuterium-filled capsule interior have now been performed. The results of these experiments are presented demonstrating a significant decrease in adiabat over previously untuned implosions. The impact of the improved shock timing is confirmed in related deuterium-tritium layered capsule implosions, which show the highest fuel compression (ρR~1.0 g/cm(2)) measured to date, exceeding the previous record V. Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010) by more than a factor of 3. The experiments also clearly reveal an issue with the 4th shock velocity, which is observed to be 20% slower than predictions from numerical simulation.
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