Review of Sensor Technology to Support Automated Air-to-Air Refueling of a Probe Configured Uncrewed Aircraft.

As technologies advance and applications for uncrewed aircraft increase, the capability to conduct automated air-to-air refueling becomes increasingly important. This paper provides a review of required sensors to enable automated air-to-air refueling for an uncrewed aircraft, as well as a review of published research on the topic. Automated air-to-air refueling of uncrewed aircraft eliminates the need for ground infrastructure for intermediate refueling, as well as the need for on-site personnel. Automated air-to-air refueling potentially supports civilian applications such as weather monitoring, surveillance for wildfires, search and rescue, and emergency response, especially when airfields are not available due to natural disasters. For military applications, to enable the Air Wing of the Future to strike at the ranges required for the mission, both crewed and uncrewed aircraft must be capable of air-to-air refueling. To cover the sensors required to complete automated air-to-air refueling, a brief history of air-to-air refueling is presented, followed by a concept of employment for uncrewed aircraft refueling, and finally, a review of the sensors required to complete the different phases of automated air-to-air refueling. To complete uncrewed aircraft refueling, the uncrewed receiver aircraft must have the sensors required to establish communication, determine relative position, decrease separation to astern position, transition to computer vision, position keep during refueling, and separate from the tanker aircraft upon completion of refueling. This paper provides a review of the twelve sensors that would enable the uncrewed aircraft to complete the seven tasks required for automated air-to-air refueling.

Checking the Pulse of Holistic and Culturally Competent Nursing Practice in Pennsylvania.

Traditionally, underrepresented racial and ethnic groups experience marginalization, leading to inequities and disparities in health and health care. A holistic approach to care delivery can help providers meet a culturally diverse patient population's unique healing needs. A systematic assessment of nurses' cultural competency practice was conducted in Pennsylvania to reveal opportunities and provide direction for holistic, culturally competent health care services. This exploratory cross-sectional descriptive study used the Cultural Competence Education and Awareness Survey (CCEAS) to examine cultural competence practices of registered nurses employed in the state of Pennsylvania. A total of 1246 registered nurses completed the survey. Respondents expressed a strong desire for cultural competency. Education and organizational infrastructure to facilitate cultural competency could be improved. Health care leaders and policy makers at all levels should explore opportunities to strengthen nurses' culturally competent practices through ongoing professional-development activities and enhanced organizational infrastructure.

Use of an electronic seizure diary in a randomized, controlled trial of natalizumab in adult participants with drug-resistant focal epilepsy.

OBJECTIVE: To analyze electronic diary (e-diary) use in a phase 2, randomized, controlled clinical trial (OPUS; NCT03283371) of natalizumab in adult participants with drug-resistant focal epilepsy. METHODS: We developed an e-diary, which incorporated an episodic seizure diary and a daily diary reminder, for use as the primary source to record participants' daily seizure activity in the OPUS phase 2 clinical trial. Participants and/or their designated caregivers made e-diary entries by selecting seizure descriptions generated in the participants' and/or caregivers' own words at the time of screening. Seizures and seizure-free days were reported for the current day and for up to 5 and 4 retrospective days, respectively. A record of seizure symptoms entered within the prior 5-day period was displayed on accessing the diary. Changes were not permitted in the e-diary once a seizure record was saved unless a data change request was made. A paper backup diary was available. RESULTS: E-diary entries (N = 15,176) from the 6-week baseline period and subsequent 24-week placebo-controlled period were analyzed for 66 adults who were randomized and dosed in the OPUS trial. The overall e-diary compliance, defined as the total number of days with any entry out of the total number of days in the baseline and placebo-controlled periods for all participants combined, was 83.6%. Caregivers made 190 (1.3%) e-diary entries. Day-of-event e-diary entries totaled 11,248 (74.1%). At least one paper backup diary was used by 36 (54.5%) participants. SIGNIFICANCE: Our data highlight that good e-diary compliance can be achieved across participants in randomized clinical trials in adult focal epilepsy. In addition to identifying and addressing any barriers that may prevent a minority of participants from achieving good e-diary compliance, consideration of e-diary elements, such as recall period and reporting of seizure-free days, will facilitate the most accurate data capture in epilepsy clinical trials.

Utility of evaluating HCV in an uninsured population.

OBJECTIVES: Although effective HCV treatment is available, it can be difficult to access for uninsured, urban patients. Our aim was to assess the utility of evaluation and outcomes in the uninsured with HCV when access to health care and treatment with triple therapy is provided. METHODS: We performed a retrospective review of consecutive patients referred for HCV from 2011 to June 2013 to an indigent HCV clinic. The primary outcomes were assessment of disease severity by noninvasive means and initiation of therapy. RESULTS: We identified 350 patients: mean age 50.6, 84 % with no insurance, 62 % men, 58 % black, 91 % HCV treatment naïve. Of these, 148 underwent liver biopsy and 68 % had F0-F1 and 10 % had F3-F4 fibrosis. FIB-4 and APRI were highly correlated (r = 0.9; p < .0001) and correctly classified patients by fibrosis strata (F0-F1, F2, and F3-F4; p = .0004). When combined, a FIB-4 ≤1.5 and APRI ≤0.5 correctly classified the absence of advanced disease in 97 % (p < .0001). Of those evaluated, 39 (11 %) went on to HCV treatment. Of those not in a clinical trial, 51 % completed treatment with SVR in 61 % with genotype 1 and 75 % in genotypenon-1. Of those not treated (n = 309), the most common reasons were mild disease (16 %), lost to follow-up (23 %), ongoing alcohol or substance abuse (24 %), and uncontrolled depression (10 %). CONCLUSION: Noninvasive assessment can accurately exclude advanced fibrosis. Despite access to care, the utility of evaluating to initiate HCV treatment is low suggesting that eliminating the barrier to health care may not increase HCV treatment.

Long term changes in liver histology following treatment of chronic hepatitis C virus.

BACKGROUND AND AIMS: The histologic hallmarks of chronic HCV include inflammation and fibrosis. The impact of interferon therapy on liver histology was evaluated. MATERIAL AND METHODS: The study population consisted of 348 patients with chronic HCV who underwent a baseline liver biopsy, received either no treatment or a single course of interferon based therapy, were followed for 5 years without any treatment or additional treatment and then underwent a repeat liver biopsy. The patients were divided into 3 groups; deferred treatment (NoTx = 47), received interferon based therapy but failed to achieve SVR (NoSVR = 189) and achieved SVR (SVR = 112). RESULTS: Patients with NoTx and NoSVR had significant increases in mean inflammation scores (from 4.3 to 6.3 and 5.4 to 6.7 respectively; p < 0.001 for both) and fibrosis scores (from 0.9 to 1.8 and 1.9 to 2.5; p < 0.001 for both). The amounts by which inflammation, fibrosis and rate of fibrosis progression increased were not significantly different between the two groups. Increases in total inflammation and the piecemeal necrosis sub-score over time were strongly associated with fibrosis progression. Patients with SVR had a significant decline in mean inflammation and fibrosis scores (from 6.7 to 2.2 and 3.3 to 1.8; p < 0.001 for both); 40% of patients resolved all fibrosis and 50% of patients resolved cirrhosis. CONCLUSION: Increases in inflammation are associated with fibrosis progression and in the absence of SVR interferon treatment does not appear to affect the long term natural history of this process. Patients with SVR have resolution of inflammation and fibrosis and many resolve cirrhosis.

Metabolic cross-talk allows labeling of O-linked beta-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway.

Hundreds of mammalian nuclear and cytoplasmic proteins are reversibly glycosylated by O-linked ß-N-acetylglucosamine (O-GlcNAc) to regulate their function, localization, and stability. Despite its broad functional significance, the dynamic and posttranslational nature of O-GlcNAc signaling makes it challenging to study using traditional molecular and cell biological techniques alone. Here, we report that metabolic cross-talk between the N-acetylgalactosamine salvage and O-GlcNAcylation pathways can be exploited for the tagging and identification of O-GlcNAcylated proteins. We found that N-azidoacetylgalactosamine (GalNAz) is converted by endogenous mammalian biosynthetic enzymes to UDP-GalNAz and then epimerized to UDP-N-azidoacetylglucosamine (GlcNAz). O-GlcNAc transferase accepts UDP-GlcNAz as a nucleotide-sugar donor, appending an azidosugar onto its native substrates, which can then be detected by covalent labeling using azide-reactive chemical probes. In a proof-of-principle proteomics experiment, we used metabolic GalNAz labeling of human cells and a bioorthogonal chemical probe to affinity-purify and identify numerous O-GlcNAcylated proteins. Our work provides a blueprint for a wide variety of future chemical approaches to identify, visualize, and characterize dynamic O-GlcNAc signaling.

Diversity Impacts of Coronavirus Disease 2019.

This article describes how coronavirus disease 2019 (COVID-19) health disparities relate to the social determinants of health and reviews the importance of a diverse nursing workforce prepared to advance social justice. The article reviews recommendations from the National Academy of Medicine and highlights practical strategies to promote diversity and social justice, including mentoring nurses from underrepresented backgrounds, amplifying diverse nursing voices, and leveraging the power of coalitions. In highlighting the interwoven impact of COVID-19 and demand for social change throughout 2020 to 2022, the article strives to move beyond the acute COVID-19 crisis to sustained social justice in health care.

Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C.

BACKGROUND: Excessive alcohol consumption is associated with an increased risk for fibrosis progression and cirrhosis in patients with chronic hepatitis C virus (HCV) infection. However, the impact of mild-moderate alcohol use on the severity of liver fibrosis is unclear. GOALS: The objective of this retrospective study was to assess the impact of mild alcohol consumption on liver fibrosis in patients with chronic HCV. STUDY: 857 patients with well-characterized chronic HCV were enrolled. All underwent liver biopsy to assess hepatic fibrosis. The duration of HCV infection was determined by detailed questionnaires and personal interviews. Alcohol use history was estimated by the Skinner Alcohol Examination Questionnaire. Mild alcohol use was defined as 1 to 3 alcoholic beverages/day (<30 grams/d). Participants were divided into 4 groups based on their average lifetime daily alcohol consumption (essentially none, <1, 1 to 3 or >3 drinks/d) and into quartiles based on their presumed duration of HCV infection (<23, 23 to 31, 31 to 38, or >38 y). RESULTS: Mean alcohol consumption was 2.7 drinks/d; mean duration of HCV infection was 29 years. Daily alcohol consumption was not significantly higher among participants with advanced fibrosis (bridging fibrosis or cirrhosis) when compared with those with none or portal fibrosis (3.2 vs. 2.2 drinks/d, respectively, P=NS). The degree of fibrosis increased significantly with the duration of HCV infection (P<0.0001) and was independent of mild-moderate alcohol consumption. CONCLUSIONS: Mild alcohol use does not seem to adversely affect the severity of fibrosis in patients with chronic HCV.

Cell surface glycoproteomic analysis of prostate cancer-derived PC-3 cells.

Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. PC-3 cells and primary human prostate cancer tissue were treated with peracetylated N-azidoacetylgalactosamine, resulting in metabolic labeling of cell surface glycans with the azidosugar. We used mass spectrometry to identify over 70 cell surface glycoproteins and biochemically validated CD146 and integrin beta-4, both of which are known to promote metastatic behavior. These results establish cell-surface glycoproteomics as an effective technique for discovery of cancer biomarkers.

Safety and Efficacy of Natalizumab as Adjunctive Therapy for People With Drug-Resistant Epilepsy: A Phase 2 Study.

BACKGROUND AND OBJECTIVES: To explore efficacy/safety of natalizumab, a humanized monoclonal anti-α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy. METHODS: Participants with ≥6 seizures during the 6-week baseline period were randomized 1:1 to receive natalizumab 300 mg IV or placebo every 4 weeks for 24 weeks. Primary efficacy outcome was change from baseline in log-transformed seizure frequency, with a predefined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group. Countable seizure types were focal aware with motor signs, focal impaired awareness, and focal to bilateral tonic-clonic. Secondary efficacy endpoints/safety were also assessed. RESULTS: Of 32 and 34 participants dosed in the natalizumab 300 mg and placebo groups, 30 (94%) and 31 (91%) completed the placebo-controlled treatment period, respectively (one participant was randomized to receive natalizumab but not dosed due to IV complications). Estimated relative change in seizure frequency of natalizumab over placebo was -14.4% (95% confidence interval [CI] -46.1%-36.1%; p = 0.51). The proportion of participants with ≥50% reduction from baseline in seizure frequency was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09, 95% CI 0.64-6.85; p = 0.22). Adverse events were reported in 24 (75%) and 22 (65%) participants receiving natalizumab vs placebo. DISCUSSION: Although the threshold to demonstrate efficacy was not met, there were no unexpected safety findings and further exploration of possible anti-inflammatory therapies for drug-resistant epilepsy is warranted. TRIAL REGISTRATION INFORMATION: The ClinicalTrials.gov registration number is NCT03283371. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that IV natalizumab every 4 weeks, compared to placebo, did not significantly change seizure frequency in adults with drug-resistant epilepsy. The study lacked the precision to exclude an important effect of natalizumab.

The Health Wagon Partners with the Virginia Department of Health to Provide COVID-19 Testing in Rural Southwest Virginia.

The Health Wagon has been providing care for the rural population of southwest Virginia for the past 40 years. The mission of the Health Wagon is to provide quality health care to the medically underserved people in the mountains of Appalachia. It has expanded to two stationary clinics, three mobile units, and a mobile dental unit, logging over 19,000 patients encounters in the past year.

Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha.

UNLABELLED: Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin (RVN) is often limited by anemia. We performed the present study to determine if utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance sustained virologic response (SVR). We randomized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups: (1) PEGIFN alpha-2b (1.5 microg/kg/week) + weight-based RVN (WBR) 13.3 mg/kg/day (800 to 1400 mg/day); (2) PEGIFN alpha-2b + WBRVN + EPO (40,000 U/week); or (3) PEGIFN alpha-2b + higher dose WBR 15.2 mg/kg/day (1000 to 1600 mg/day) + EPO. We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required, we reduced RVN by 200-mg steps. African Americans compose 36% of the population. A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL (9% versus 34%; P < 0.05) and required that the RVN dose be reduced (10% versus 40%; P < 0.05) compared to group 1 patients. Despite this, SVR was similar in these groups (19% to 29%). SVR was significantly greater (P < 0.05) in group 3 patients (49%). This resulted from a significant decline (P < 0.05) in relapse rate; only 8% versus 38% for groups 1 and 2. CONCLUSION: We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN. In contrast, a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR.

A chemical reporter strategy to probe glycoprotein fucosylation.

Fucosylated glycoproteins are involved in many cell-cell recognition events and are markers of embryonic and malignant tissue. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label.

Molecular basis for G protein control of the prokaryotic ATP sulfurylase.

Sulfate assimilation is a critical component of both primary and secondary metabolism. An essential step in this pathway is the activation of sulfate through adenylation by the enzyme ATP sulfurylase (ATPS), forming adenosine 5'-phosphosulfate (APS). Proteobacterial ATPS overcomes this energetically unfavorable reaction by associating with a regulatory G protein, coupling the energy of GTP hydrolysis to APS formation. To discover the molecular basis of this unusual role for a G protein, we biochemically characterized and solved the X-ray crystal structure of a complex between Pseudomonas syringae ATPS (CysD) and its associated regulatory G protein (CysN). The structure of CysN*D shows the two proteins in tight association; however, the nucleotides bound to each subunit are spatially segregated. We provide evidence that conserved switch motifs in the G domain of CysN allosterically mediate interactions between the nucleotide binding sites. This structure suggests a molecular mechanism by which conserved G domain architecture is used to energetically link GTP turnover to the production of an essential metabolite.