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BACKGROUND The American Heart Association funded a Health Equity Research Network on the prevention of hypertension, the RESTORE Network, as part of its commitment to achieving health equity in all communities. This article provides an overview of the RESTORE Network. METHODS The RESTORE Network includes five independent, randomized trials testing approaches to implement non-pharmacological interventions that have been proven to lower blood pressure (BP). The trials are community-based, taking place in churches in rural Alabama, mobile health units in Michigan, barbershops in New York, community health centers in Maryland, and food deserts in Massachusetts. Each trial employs a hybrid effectiveness-implementation research design to test scalable and sustainable strategies that mitigate social determinants of health (SDOH) that contribute to hypertension in Black communities. The primary outcome in each trial is change in systolic BP. The RESTORE Network Coordinating Center has five cores: BP measurement, statistics, intervention, community engagement, and training that support the trials. Standardized protocols, data elements and analysis plans were adopted in each trial to facilitate cross-trial comparisons of the implementation strategies, and application of a standard costing instrument for health economic evaluations, scale up, and policy analysis. Herein, we discuss future RESTORE Network research plans and policy outreach activities designed to advance health equity by preventing hypertension. CONCLUSIONS The RESTORE Network was designed to promote health equity in the US by testing effective and sustainable implementation strategies focused on addressing SDOH to prevent hypertension among Black adults.

OBJECTIVE Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients. METHODS A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors’ institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures. RESULTS Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS. CONCLUSIONS The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

Patients with complex polytrauma in the military and civilian settings are often exposed to substantial diagnostic medical radiation because of serial imaging studies for injury diagnosis and subsequent management. This cumulative radiation exposure may increase the risk of subsequent malignancy. This is particularly true for combat-injured servicemembers who receive care at a variety of facilities worldwide. Currently, there is no coordinated effort to track the amount of radiation exposure each servicemember receives, nor a surveillance program to follow such patients in the long term. It is important to assess whether military servicemembers are exposed to excessive diagnostic radiation to mitigate or prevent such occurrences and monitor for carcinogenesis, when necessary. The cumulative amount of radiation exposure for combat-wounded and noncombat-wounded servicemembers has not been described, and it remains unknown whether diagnostic radiation exposure meets thresholds for an increased risk of carcinogenesis.We performed this study to (1) quantify the amount of exposure for combat-wounded servicemembers based on medical imaging in the first year after injury and compare those exposures with noncombat-related trauma, and (2) determine whether the cumulative dose of radiation correlates to the Injury Severity Score (ISS) across the combat-wounded and noncombat-wounded population combined.We performed a retrospective study of servicemembers who sustained combat or noncombat trauma and were treated at Walter Reed National Military Medical Center from 2005 to 2018. We evaluated patients using the Department of Defense Trauma Registry. After consolidating redundant records, the dataset included 3812 unique servicemember encounters. Three percent (104 of 3812) were excluded because of missing radiation exposure data in the electronic medical record. The final cohort included 3708 servicemembers who had combat or noncombat injury trauma, with a mean age at the time of injury of 26 ± 6 years and a mean ISS of 18 ± 12. The most common combat trauma mechanisms of injury were blast (in 65% [2415 of 3708 patients]), followed by high-velocity gunshot wounds (in 22% [815 of 3708 patients]). We calculated the cumulative diagnostic radiation dose exposure at 1 year post-traumatic injury in patients with combat-related trauma and those with noncombat trauma. We did this by multiplying the number of imaging studies by the standardized effective radiation dose for each imaging study type. We then performed analysis of variance for four data subsets (battle combat trauma, nonbattle civilian trauma, high ISS, and high radiation exposure [50 mSv]) independently. To evaluate whether the total number of imaging studies, radiation exposure, and ISS values differed between battle-wounded and nonbattle-wounded patients, we performed a pairwise t-test.The mean radiation exposure for combat-related injuries was 35 ± 26 mSv while the mean radiation exposure for noncombat-related injuries was 22 ± 33 mSv in the first year after injury. In the first year after trauma, 44% of patients (1626 of 3708) were exposed to high levels of radiation that were greater than 20 mSv, and 23% (840 of 3708) were exposed to very high levels of radiation that were greater than 50 mSv. Servicemembers with combat trauma-related injuries had eight more imaging studies than those who sustained noncombat injuries. Servicemembers with combat trauma injuries (35 ± 26 mSv) were exposed to more radiation (approximately 4 mSv) than patients treated for noncombat injuries (22 ± 33 mSv) (p = 0.01). We found that servicemembers with combat injuries had a higher ISS than servicemembers with noncombat trauma (p0.001). We found a positive correlation between radiation exposure and ISS for servicemembers. The positive relationship between radiation exposure and ISS held for combat trauma (r2 = 0.24; p0.001), noncombat trauma (r2 = 0.20; p0.001), servicemembers with a high ISS (r2 = 0.10; p0.001), and servicemembers exposed to high doses of radiation (r2 = 0.09; p0.001).These data should be used during clinical decision-making and patient counseling at military treatment facilities and might provide guidance to the Defense Health Agency. These recommendations will help determine whether the benefits of further imaging outweigh the risk of carcinogenesis. If not, we need to develop interdisciplinary clinical practice guidelines to reduce or minimize radiation exposure. It is important for treating physicians to seriously weigh the risk and benefits of every imaging study ordered because each test does not come without a cumulative risk.Level III, therapeutic study.

After five years of research on microplastic pollution of soils it becomes obvious that soil systems act as a reservoir for microplastics on global scales. Nevertheless, the exact role of soils within global microplastic cycles, plastic fluxes within soils and environmental consequences are so far only partly understood. Against the background of a global environmental plastic pollution, the spatial reference, spatial levels, sampling approaches and documentation practices of soil context data becomes important. Within this review, we therefore evaluate the availability of spatial MP soil data on a global scale through the application of a questionnaire applied to 35 case studies on microplastics in soils published since 2016. We found that the global database on microplastics in soils is mainly limited to agricultural used topsoils in Central Europe and China. Data on major global areas and soil regions are missing, leading to a limited understanding of soils plastic pollution. Furthermore, we found that open data handling, geospatial data and documentation of basic soil information are underrepresented, which hinders further understanding of global plastic fluxes in soils. Out of this context, we give recommendations for spatial reference and soil context data collection, access and combination with soil microplastic data, to work towards a global and free soil microplastic data hub.

Glacier motion responds dynamically to changing meltwater inputs, but the multi-decadal response of basal sliding to climate remains poorly constrained due to its sensitivity across multiple timescales. Observational records of glacier motion provide critical benchmarks to decode processes influencing glacier dynamics, but multi-decadal records that precede satellite observation and modern warming are rare. Here we present a record of motion in the ablation zone of Saskatchewan Glacier that spans seven decades. We combine in situ and remote-sensing observations to inform a first-order glacier flow model used to estimate the relative contributions of sliding and internal deformation on dynamics. We find a significant increase in basal sliding rates between melt-seasons in the 1950s and those in the 1990s and 2010s and explore three process-based explanations for this anomalous behavior: (i) the glacier surface steepened over seven decades, maintaining flow-driving stresses despite sustained thinning; (ii) the formation of a proglacial lake after 1955 may support elevated basal water pressures; and (iii) subglacial topography may cause dynamic responses specific to Saskatchewan Glacier. Although further constraints are necessary to ascertain which processes are of greatest importance for Saskatchewan Glacier's dynamic evolution, this record provides a benchmark for studies of multi-decadal glacier dynamics.

Background As genome sequencing becomes better integrated into scientific research, government policy, and personalized medicine, the primary challenge for researchers is shifting from generating raw data to analyzing these vast datasets. Although much work has been done to reduce compute times using various configurations of traditional CPU computing infrastructures, Graphics Processing Units (GPUs) offer opportunities to accelerate genomic workflows by orders of magnitude. Here we benchmark one GPU-accelerated software suite called NVIDIA Parabricks on Amazon Web Services (AWS), Google Cloud Platform (GCP), and an NVIDIA DGX cluster. We benchmarked six variant calling pipelines, including two germline callers (HaplotypeCaller and DeepVariant) and four somatic callers (Mutect2, Muse, LoFreq, SomaticSniper). Results We achieved up to 65 × acceleration with germline variant callers, bringing HaplotypeCaller runtimes down from 36 h to 33 min on AWS, 35 min on GCP, and 24 min on the NVIDIA DGX. Somatic callers exhibited more variation between the number of GPUs and computing platforms. On cloud platforms, GPU-accelerated germline callers resulted in cost savings compared with CPU runs, whereas some somatic callers were more expensive than CPU runs because their GPU acceleration was not sufficient to overcome the increased GPU cost. Conclusions Germline variant callers scaled well with the number of GPUs across platforms, whereas somatic variant callers exhibited more variation in the number of GPUs with the fastest runtimes, suggesting that, at least with the version of Parabricks used here, these workflows are less GPU optimized and require benchmarking on the platform of choice before being deployed at production scales. Our study demonstrates that GPUs can be used to greatly accelerate genomic workflows, thus bringing closer to grasp urgent societal advances in the areas of biosurveillance and personalized medicine.

Table S2. Differential AS events between PC-3E and GS689.Li

Figure S1. The effects of EMT-relevant transcription factors on NOVA1 protein expression

Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life. Male and female mice were tested several weeks later using novel object recognition (recognition memory) and 5-choice serial reaction time task (executive function). Gene expression of proinflammatory, white matter and synapse-associated molecules was assessed in the prefrontal cortex and small intestine both acutely after chemotherapy and chronically after cognitive testing. Early life cancer-chemotherapy exposure resulted in recognition memory and executive function deficits in adult male mice. Prefrontal cortex expression of the chemokine Ccl2 was increased acutely, while small intestine expression of the proinflammatory cytokine tumor necrosis factor-alpha was elevated both acutely (both sexes) and chronically (males only). Inflammation in the small intestine was correlated with prefrontal cortical proinflammatory and synaptic gene expression changes, as well as to executive function deficits. Collectively, these data indicate that the current protocol results in a robust mouse model in which to study cognitive deficits in leukemia survivors, and suggest that small intestine inflammation may represent a novel contributor to adverse CNS consequences of early life chemotherapy.

This study aimed to: (1) develop an integrated approach to quantifying match physical-tactical performance and (2) comprehensively examine the validity and reliability of this novel approach. Both UEFA qualified coaches and performance analysts (n = 30) participated to verify the scientific robustness of this new method. The percentage of correct responses were used to verify the validity of the integrated approach and the minimum acceptable agreement was set at 80%. Two well-trained groups of observers analysed a randomly selected English Premier League match for inter- and intra-observer reliability using the kappa statistic. A high degree of validity was demonstrated as the mean percentage of correct responses by all participants, accounting for 91.8 ± 4.3% for all, 92.2 ± 4.7% for out-of-possession, and 91.6 ± 5.7% for in-possession physical-tactical variables. Inter- and intra-observer reliability were found to be strong (κ = 0.81) to almost perfect (κ = 0.94), respectively. Additional analyses demonstrated that there was a nearly perfect correlation between data derived from the novel filter used for the present study to capture high-intensity running and those obtained from the filter of the commercial data provider (r = 0.99; P

Microplastics (MPs) as polymeric environmental pollutants have been detected worldwide within arable soils. As agricultural practice poses direct input pathways for plastics to soils and carry the risk of endangering important soil functions, soils microplastic community has developed a strong focus on the investigation on MPs within arable land. However, data on large scale spatial as well as temporal MP occurrence in agricultural soils is still lacking. One possible way to access both, spatial and temporal variance of MPs in agricultural soils is the analysis of reserve samples from permanent soil observation (PSO) monitoring programmes. Based on the example of the PSO programme within the federal state of Hesse (Germany) we have analysed microplastics (300–5000 µm) from topsoil samples of 16 PSO locations sampled in 2003/2004 and 2014/2019. The PSO locations include 12 croplands, three grasslands and one forest soil as a control site across the federal state and its major soilscapes with typical soil formations. We used a MP extraction protocol based on density separation, Nile Red staining and fluorescent analysis coupled with a polymer analysis via ATR-FTIR. Own spiking experiments for common polymers yielded recovery rates of 100% for large MPs (>1000 µm) and 92% for MPs above our lower detection limit of 300 µm. We found MP concentrations of 34.80±23.37 p kg-1 with increasing concentrations by decreasing particle sizes. Overall, MPs occurred dominantly as films, followed by fragments and filaments made of PEs, synthetic rubbers or EPDMs, followed by common thermoplastic polymers. With regard to land use and soil management practice, MP concentrations were significant higher in grassland soils than cropland soils, while particle sizes and polymeric composition stay consistent. Surprisingly, we found the highest MP concentration of 65.22 p kg-1 within mineral forest topsoils of a remote low mountain area. A clear temporal trend, like the MP concentration increase over time, was not detectable. Moreover, we found high temporal variances depending on PSO locations. However, MP concentrations are significant higher at PSO locations in short distances to urban areas, indicating the role of land use intensity and potential littering as MP sources. Our findings enable a discussion on large scale plastic input pathways and their temporal variance. Furthermore, different questions about spatial contaminant patterns and the long-term behaviour of plastics in soils have been raised, that should be discussed within our contribution.

Additional file 1. Additional results of benchmarking on AWS. Table S1 shows NVIDIA A100 GPU machine benchmarking results, and figures show benchmarking the NVIDIA V100 GPU machine.

There is an unmet need for fully automated image prescription of the liver to enable efficient, reproducible MRI.To develop and evaluate artificial intelligence (AI)-based liver image prescription.Prospective.A total of 570 female/469 male patients (age: 56 ± 17 years) with 72%/8%/20% assigned randomly for training/validation/testing; two female/four male healthy volunteers (age: 31 ± 6 years).1.5 T, 3.0 T; spin echo, gradient echo, bSSFP.A total of 1039 three-plane localizer acquisitions (26,929 slices) from consecutive clinical liver MRI examinations were retrieved retrospectively and annotated by six radiologists. The localizer images and manual annotations were used to train an object-detection convolutional neural network (YOLOv3) to detect multiple object classes (liver, torso, and arms) across localizer image orientations and to output corresponding 2D bounding boxes. Whole-liver image prescription in standard orientations was obtained based on these bounding boxes. 2D detection performance was evaluated on test datasets by calculating intersection over union (IoU) between manual and automated labeling. 3D prescription accuracy was calculated by measuring the boundary mismatch in each dimension and percentage of manual volume covered by AI prescription. The automated prescription was implemented on a 3 T MR system and evaluated prospectively on healthy volunteers.Paired t-tests (threshold = 0.05) were conducted to evaluate significance of performance difference between trained networks.In 208 testing datasets, the proposed method with full network had excellent agreement with manual annotations, with median IoU 0.91 (interquartile range 0.09) across all seven classes. The automated 3D prescription was accurate, with shifts2.3 cm in superior/inferior dimension for 3D axial prescription for 99.5% of test datasets, comparable to radiologists' interreader reproducibility. The full network had significantly superior performance than the tiny network for 3D axial prescription in patients. Automated prescription performed well across single-shot fast spin-echo, gradient-echo, and balanced steady-state free-precession sequences in the prospective study.AI-based automated liver image prescription demonstrated promising performance across the patients, pathologies, and field strengths studied.4.Stage 1.

Staufen1 (STAU1) is a multifunctional RNA binding protein that controls mRNA degradation and subcellular localization. STAU1 interacts with the ATXN2 protein, that is polyglutamine expanded in spinocerebellar ataxia type 2 (SCA2). We previously showed that STAU1 is elevated and aggregated in cells from SCA2 patients, cells from amyotrophic lateral sclerosis (ALS) patients, and in SCA2 and ALS mouse models. We also found that reduction of STAU1 abundancein vivoby genetic interaction improved motor behavior in an SCA2 mouse model, normalized the levels of several SCA2-related proteins, and reduced aggregation of polyglutamine-expanded ATXN2. Here we developed antisense oligonucleotides (ASOs) lowering STAU1 expression toward developing a therapeutic that may be effective for treating SCA2 and ALS. We performed a screen of 118 20mer phosphorothioate 2’-O-methoxyethyl (MOE) ASO gapmers targeting across theSTAU1mRNA coding region for lowering STAU1 expression in HEK-293 cells. ASO hits lowering STAU1 by >45 % were rescreened in SCA2 patient fibroblasts, and 10 of these were tested for lowering STAU1 abundancein vivoin a new BAC-STAU1 mouse model. This identified efficacious ASOs targeting humanSTAU1 in vivothat normalized autophagy marker proteins, including ASO-45 that also targets mouseStau1. When delivered by intracerebroventricular (ICV) injection, ASO-45 normalized autophagy markers and abnormal mRNA abundances in cerebella of ATXN2-Q127 SCA2 mice, as well as ChAT, NeuN and cleaved caspase-3 in spinal cord ofThy1-TDP-43 transgenic mice. TargetingSTAU1may be an effective strategy for treating ALS and SCA2 as well as other disorders characterized by its overabundance.

Model-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.All three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly ( 10%) at a reduction factor up to 8. In prostate data, the quantitative estimation of the conversion-rate constant of pyruvate to lactate was achieved with high accuracy of less than 10% error at a reduction factor of 2 compared with the conversion rate derived from unaccelerated data.The MoReFUn technique can be used as an effective and reliable imaging acceleration method for metabolic imaging using hyperpolarized [1

Sarcoidosis is a granulomatous disease of unknown etiology but is theorized to result from immune overactivity in the setting of an environmental or genetic trigger. It most commonly affects the lungs and lymph nodes but can affect other organ systems, with cutaneous involvement in 30% of patients. The granulomas associated with sarcoidosis lead to increased activity of angiotensin-converting enzyme (ACE) and 1α-hydroxylase resulting in an uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages, along with elevated serum ACE and calcium levels. Serum ACE and calcium levels are frequently ordered when a patient is diagnosed with cutaneous sarcoidosis. However, their clinical utility in this setting remains unknown.In this retrospective chart review, we assessed serum ACE and calcium levels in 19 patients with cutaneous sarcoidosis diagnosed by histopathology without preceding evidence of systemic involvement. Serum ACE and calcium levels were also investigated as markers in the progression from mono-organ cutaneous sarcoidosis to systemic sarcoidosis.No patients with biopsy-proven cutaneous sarcoidosis had abnormal levels of serum calcium at presentation in a cohort of 17 patients at a single institution. An abnormally elevated ACE level was only seen in one of 13 patients presenting with cutaneous sarcoidosis.Our data suggest that serum ACE and calcium levels are not reliable markers of either cutaneous sarcoidosis or the progression to systemic sarcoidosis.

Predictive models are increasingly being developed and implemented to improve patient care across a variety of clinical scenarios. While a body of literature exists on the development of models using existing data, less focus has been placed on practical operationalization of these models for deployment in real-time production environments. This case-study describes challenges and barriers identified and overcome in such an operationalization for a model aimed at predicting risk of outpatient falls after Emergency Department (ED) visits among older adults. Based on our experience, we provide general principles for translating an EHR-based predictive model from research and reporting environments into real-time operation.

Purpose A specialized Helmholtz-style 13 C volume transmit "clamshell" coil is currently being utilized for 13 C excitation in pre-clinical and clinical hyperpolarized 13 C MRI studies aimed at probing the metabolic activity of tumors in various target anatomy. Due to the widespread use of this 13 C clamshell coil design, it is important that the effects of the 13 C clamshell coil B1 + profile on HP signal evolution and quantification are well understood. The goal of this study was to characterize the B1 + field of the 13 C clamshell coil and assess the impact of inhomogeneities on semi-quantitative and quantitative hyperpolarized MR imaging biomarkers of metabolism. Methods The B1 + field of the 13 C clamshell coil was mapped by hand using a network analyzer equipped with an S-parameter test set. Pharmacokinetic models were used to simulate signal evolution as a function of position-dependent local excitation angles, for various nominal excitation angles, which were assumed to be accurately calibrated at the isocenter. These signals were then quantified according to the normalized lactate ratio (nLac) and the apparent rate constant for the conversion of pyruvate to lactate (kPL ). The percent difference between these metabolic imaging biomarker maps and the reference value observed at the isocenter of the clamshell coil was calculated to estimate the potential for error due to position within the clamshell coil. Finally, regions were identified within the clamshell coil where deviations in B1 + field inhomogeneity or imaging biomarker errors imparted by the B1 + field were within ±10% of the value at the isocenter. Results The B1 + field maps show that a limited volume encompassed by a region measuring approximately 12.9 × 11.5 × 13.4 cm (X-direction, Y-direction, Z-direction) centered in the 13 C clamshell coil will produce deviations in the B1 + field within ±10% of that at the isocenter. For the metabolic imaging biomarkers that we evaluated, the case when the pyruvate excitation angle (θP ) and lactate excitation angle (θL ) were equal to 10° produced the largest volumetric region with deviations within ±10% of the value at the isocenter. Higher excitation angles yielded higher signal and SNR, but the size of the region in which uniform measurements could be collected near the isocenter of the coil was reduced at higher excitation angles. The tradeoff between the size of the homogenous region at the isocenter and signal intensity must be weighed carefully depending on the particular imaging application. Conclusion This work identifies regions and optimal excitation angles (θP and θL ) within the 13 C clamshell coil where deviations in B1 + field inhomogeneity or imaging biomarker errors imparted by the B1 + field were within ±10% of the respective value at the isocenter, and thus where excitation angles are reproducible and well-calibrated. Semi-quantitative and quantitative metabolic imaging biomarkers can vary with position in the clamshell coil as a result of B1 + field inhomogeneity, necessitating care in patient positioning and the selection of an excitation angle set that balances reproducibility and SNR performance over the target imaging volume.

Disturbances are critical for maintaining environmental heterogeneity and biodiversity across landscapes. Hurricanes represent a common disturbance in the Caribbean Sea. These storms are predicted to become more frequent and severe as climate shifts. Understanding how island communities respond to disturbances is critical to their conservation. We surveyed Virgin Islands National Park located on the island of St. John in the Caribbean Sea in 2016 and 2018 to evaluate prolonged herpetofauna community response and resistance to hurricanes. These surveys occurred in March 2016, and June 2018, before and after the 2017 hurricane season, when hurricanes Irma and Maria struck St. John. Using visual encounter surveys, vocalisation surveys, and opportunistic encounters, we surveyed trails within the park through five landscape cover types pre- and post-hurricane. We used linear regression to determine differences in diversity and species richness among landscape cover types and between pre- and post-hurricane surveys and non-metric multidimensional scaling to observe associations among species and landscape cover types pre- and post-hurricane surveys. We determined that there were no significant changes in landscape cover and herpetofauna community associations before and after the 2017 hurricane season, indicating that the herpetofauna communities of Virgin Islands National Park are well adapted to hurricane-related disturbance.

We investigate a laser direct-write method to synthesize and deposit metastable, mixed transition metal oxides and evaluate their performance as oxygen evolution reaction catalysts. This laser processing method enabled the rapid synthesis of diverse heterogeneous alloy and oxide catalysts directly from cost-effective solution precursors, including catalysts with a high density of nanocrystalline metal alloy inclusions within an amorphous oxide matrix. The nanoscale heterogeneous structures of the synthesized catalysts were consistent with reactive force-field Monte Carlo calculations. By evaluating the impact of varying transition metal oxide composition ratios, we created a stable Fe0.63Co0.19Ni0.18Ox/C catalyst with a Tafel slope of 38.23 mV dec-1 and overpotential of 247 mV, a performance similar to that of IrO2. Synthesized Fe0.63Co0.19Ni0.18Ox/C and Fe0.14Co0.46Ni0.40Ox/C catalysts were experimentally compared in terms of catalytic performance and structural characteristics to determine that higher iron content and a less crystalline structure in the secondary matrix decrease the charge transfer resistance and thus is beneficial for electrocatalytic activity. This conclusion is supported by density-functional theory calculations showing distorted active sites in ternary metal catalysts are key for lowering overpotentials for the oxygen evolution reaction.

Risk mitigation strategies commonly use the test uncertainty ratio (TUR) and end-of-period reliability (EOPR) to ensure a measurement is adequate for making acceptance decisions. Unfortunately, the common guidance of maintaining a TUR of at least 4:1 was developed to simplify the underlying calculus in an era predating modern computing and assumes that the probability distributions describing the product and the measurement uncertainty are unbiased and normally distributed. The Guide to the Expression of Uncertainty in Measurement and its supplements describe several situations where uncertainty in the measurement will not follow a normal distribution. Despite the evidence of non-normal behavior in measurements and products, risk evaluations typically assume normality in both distributions. While evaluating the probability of false accept (PFA) and the probability of false reject (PFR) is more challenging when the probability distributions are non-normal, the calculus is straightforward using either numerical integration or Monte Carlo techniques. This work considers several case studies of risk evaluation, including both global and specific risk, when the product or the test measurement uncertainty do not follow normal distributions. Neglecting non-normal behavior might greatly affect PFA and PFR by either over- or underestimating the probabilities depending on the parameters of the distributions.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive, lethal, heterogeneous type of breast cancer (BC). TNBC tends to have a lower response rate to chemotherapy and a lower fiveyear survival rate than other types of BC due to recurrence and metastasis. Our previous study revealed that a combination of gemcitabine, romidepsin, and cisplatin was efficacious in controlling TNBC tumor development. In this study, we extended our investigation of gemcitabine+romidepsin+cisplatin in controlling TNBC tumor recurrence and metastasis. METHODS: We investigated the ability of gemcitabine+romidepsin+cisplatin to control cell survival and invasiveness using cell viability, soft agar colony formation, and transwell invasion assays. We determined the efficacy of gemcitabine+romidepsin+cisplatin in controlling tumor recurrence and metastasis using cell-derived xenograft animal models. We used immunoblotting to study signaling modulators regulated by gemcitabine+romidepsin+cisplatin in TNBC cells and tumor tissues. RESULTS: Treatment with gemcitabine+romidepsin+cisplatin reduced the TNBC MDA-MB231 and MDA-MB468 cell survival to ~50% and ~15%, as well as invasiveness to ~31% and ~13%, respectively. Gemcitabine+romidepsin+cisplatin suppressed modulators involved in epithelialmesenchymal transition in an ROS-dependent manner. Controlling tumor recurrence, the Gem plus Rom+Cis regimen (~112%) was more efficacious than the Gem plus Cis regimen (~21%) in tumor growth inhibition. The Gem plus Rom+Cis regimen efficaciously reduced the development of metastatic nodules to 20% in animals. CONCLUSION: The gemcitabine plus romidepsin+cisplatin regimen was highly efficacious in controlling TNBC tumor development, recurrence, and metastasis in animals. The combination regimen should be poised for efficient translation into clinical trials for controlling the recurrence and metastasis, ultimately contributing to reducing mortality and improving TNBC patients’ quality of life.

New-onset refractory status epilepticus (NORSE) is a rare neurological emergency in which a patient without prior seizure disorder develops seemingly unprovoked status epilepticus refractory to treatment. We report the case of a middle-aged woman who developed NORSE after receiving multiple blood transfusions for subacute blood loss anemia secondary to menorrhagia. Although the mechanism is unclear, we propose that sudden changes in blood viscosity and vasogenic tone resulted in cortical edema and irritation. Although seizures have been documented in patients who undergo blood transfusion and develop posterior reversible encephalopathy syndrome (PRES), there was no radiographic evidence of PRES in this case. This is the first reported case of cryptogenic NORSE following blood transfusion.

The standard of care for idiopathic normal pressure hydrocephalus (iNPH) is placement of a ventriculoperitoneal (VP) shunt. However, VP shunts require intracranial intervention and are associated with notable postoperative complications, with some groups reporting complication rates for VP shunts ranging from 17 to 33%, along with failure rates up to 17.7%. Lumboperitoneal (LP) shunts are an alternative for cerebrospinal fluid diversion that do not require intracranial surgery, thus providing utility in patients where intracranial surgery is not possible or preferred. Here we retrospectively reviewed our 25 patients with LP horizontal-vertical (LP-HV) shunts placement for initial treatment for iNPH from 2014 to 2019. All patients had preoperative gait dysfunction, 16 (64%) had urinary incontinence, and 21 (84%) exhibited cognitive insufficiency. Two weeks post-shunt placement, 23/25 (92%) patients demonstrated improvement in gait, 11/16 (68%) had improvement in incontinence, and 14/21 (66%) had improvement cognitive insufficiency. At six months or greater follow up 13/20 (65%) had improvement in gait, 7/15 (47%) showed improvement in incontinence, and 11/15 (73%) demonstrated improvement in cognitive function. Six patients (24%) required at least one revision of the LP shunt. Shunt malfunctions resulted from CSF leak in one patient, shunt catheter migration in two patients, peritoneal catheter pain in one patient, and clinical symptoms for overdrainage in two patients. Thus, we demonstrate that LP-HV shunt placement is safe and efficacious alternative to VP shunting for iNPH, resulting in notable symptomatic improvement and low risk of overdrainage, and may be considered for patients where cranial approaches should be avoided.