NPS career forward

"NPS provided a critical link in my career from warfighting operator to strategic thinker and reasoner. I found the education at NPS to be superior in every respect, and I enrolled in as many classes as was physically possible during my time there so that I could take advantage of the expertise and resources that were available. My NPS education, as well as the Strategic Group XIX fellowship formulated many of the current initiatives for my Joint UAS Concepts team."US Navy (USN) autho

Setting and motivation in the decision to participate: An approach to the engagement of diverse samples in mobile research.

Internet and mobile based research are powerful tools in the creation of large, cohort studies (eCohort). However, recent analysis indicates that an underrepresentation of minority and low income groups in these studies might exceed that found in traditional research [1-5]. In this report, we present findings from an experiment in research engagement using the Eureka Research Platform developed to enroll diverse populations in support of biomedical clinical research. This experiment involved the recruitment of African American and Latino participants in a smartphone based survey at a temporary, charitable, dental event sponsored, in part, by the research team, in order to explore the impact of setting and approach on recruitment outcomes. 211 participants enrolled including a significant representation of African Americans (51%) and Latinos (31%) and those with education levels at high school or less (37%). Interviews conducted after the study confirmed that our recruitment efforts within the context of a service event affected the decision to participate. While further research is necessary, this experiment holds promise for the engagement of underrepresented groups in research

DeepHeart: Semi-Supervised Sequence Learning for Cardiovascular Risk Prediction

We train and validate a semi-supervised, multi-task LSTM on 57,675 person-weeks of data from off-the-shelf wearable heart rate sensors, showing high accuracy at detecting multiple medical conditions, including diabetes (0.8451), high cholesterol (0.7441), high blood pressure (0.8086), and sleep apnea (0.8298). We compare two semi-supervised train- ing methods, semi-supervised sequence learning and heuristic pretraining, and show they outperform hand-engineered biomarkers from the medical literature. We believe our work suggests a new approach to patient risk stratification based on cardiovascular risk scores derived from popular wearables such as Fitbit, Apple Watch, or Android Wear.Comment: Presented at AAAI 201

Long-Term Restoration of Rod and Cone Vision by Single Dose rAAV-Mediated Gene Transfer to the Retina in a Canine Model of Childhood Blindness

The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations

Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection.

Patients with cardiovascular comorbidities are more susceptible to severe infection with SARS-CoV-2, known to directly cause pathological damage to cardiovascular tissue. We outline a screening platform using human embryonic stem cell-derived cardiomyocytes, confirmed to express the protein machinery critical for SARS-CoV-2 infection, and a SARS-CoV-2 spike-pseudotyped virus system. The method has allowed us to identify benztropine and DX600 as novel inhibitors of SARS-CoV-2 infection in a clinically relevant stem cell-derived cardiomyocyte line. Discovery of new medicines will be critical for protecting the heart in patients with SARS-CoV-2, and for individuals where vaccination is contraindicated

IEA-Task 31 WAKEBENCH: Towards a protocol for wind farm flow model evaluation. Part 1: Flow-over-terrain models

The IEA Task 31 Wakebench is setting up a framework for the evaluation of wind farm flow models operating at microscale level. The framework consists on a model evaluation protocol integrated on a web-based portal for model benchmarking (www.windbench.net). This paper provides an overview of the building-block validation approach applied to flow-over-terrain models, including best practices for the benchmarking and data processing procedures for the analysis and qualification of validation datasets from wind resource assessment campaigns. A hierarchy of test cases has been proposed for flow-over-terrain model evaluation, from Monin-Obukhov similarity theory for verification of surface-layer properties, to the Leipzig profile for the near-neutral atmospheric boundary layer, to flow over isolated hills (Askervein and Bolund) to flow over mountaneous complex terrain (Alaiz). A summary of results from the first benchmarks are used to illustrate the model evaluation protocol applied to flow-over-terrain modeling in neutral conditions

Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites.

ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent 'Long COVID'. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.This research was funded in whole, or in part by: Wellcome Trust (WT107715/Z/15/Z, A.P.D., and J.J.M.); Wellcome Trust Programme in Metabolic and Cardiovascular Disease (203814/Z/16/A, T.L.W., D.N.), Wellcome Trust Major Award (208363/Z/17/Z) for Imaging Core (G.S.); British Heart Foundation (FS/17/61/33473 A.P.D., R.G.C.M; TG/18/4/33770, A.P.D., J.J.M.; FS/18/46/33663, S.S.). Cambridge Biomedical Research Centre Biomedical Resources Grant (University of Cambridge, Cardiovascular Theme, RG64226). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

A surrogate method for comparison analysis of salivary concentrations of Xylitol-containing products

Background: Xylitol chewing gum has been shown to reduce Streptococcus mutans levels and decay. Two studies examined the presence and time course of salivary xylitol concentrations delivered via xylitol-containing pellet gum and compared them to other xylitol-containing products. Methods: A within-subjects design was used for both studies. Study 1, adults (N = 15) received three xylitol-containing products (pellet gum (2.6 g), gummy bears (2.6 g), and commercially available stick gum (Koolerz, 3.0 g)); Study 2, a second group of adults (N = 15) received three xylitol-containing products (pellet gum, gummy bears, and a 33% xylitol syrup (2.67 g). For both studies subjects consumed one xylitol product per visit with a 7-day washout between each product. A standardized protocol was followed for each product visit. Product order was randomly determined at the initial visit. Saliva samples (0.5 mL to 1.0 mL) were collected at baseline and up to 10 time points (~16 min in length) after product consumption initiated. Concentration of xylitol in saliva samples was analyzed using high-performance liquid chromatography. Area under the curve (AUC) for determining the average xylitol concentration in saliva over the total sampling period was calculated for each product. Results: In both studies all three xylitol products (Study 1: pellet gum, gummy bears, and stick gum; Study 2: pellet gum, gummy bears, and syrup) had similar time curves with two xylitol concentration peaks during the sampling period. Study 1 had its highest mean peaks at the 4 min sampling point while Study 2 had its highest mean peaks between 13 to 16 minutes. Salivary xylitol levels returned to baseline at about 18 minutes for all forms tested. Additionally, for both studies the total AUC for the xylitol products were similar compared to the pellet gum (Study 1: pellet gum - 51.3 [micro]g.min/mL, gummy bears - 59.6 [micro]g.min/mL, and stick gum - 46.4 [micro]g.min/mL; Study 2: pellet gum - 63.0 [micro]g.min/mL, gummy bears - 55.9 [micro]g.min/mL, and syrup - 59.0 [micro]g.min/mL). Conclusion: The comparison method demonstrated high reliability and validity. In both studies other xylitol-containing products had time curves and mean xylitol concentration peaks similar to xylitol pellet gum suggesting this test may be a surrogate for longer studies comparing various products.NIDCR-NIH U54 DE14254; Head Start, HRSA 90YD0188/03; and MCHB, HRSA R40MC03622-03