Generalized inverse with shipboard current measurements: Tidal and nontidal flows in Long Island Sound

A simple linear shallow-water model forced by tidal boundary conditions can capture most of the tide height variability in Long Island Sound. In this sense, the tides are easy to model. The modeled tidal currents can be subtracted from measurements in order to obtain estimates of subtidal circulation. But linear shallow-water dynamics is not accurate enough for this purpose. Allowing for dynamical errors with a generalized inverse model leads to improved estimates of tidal and nontidal flow. The analysis provides expected errors for the prior (before inversion) and posterior (after inversion) tidal velocity field. Estimates of the flow field in central Long Island Sound are obtained with current measurements from a ship-mounted Acoustic Doppler Current Profiler (ADCP) survey. Inversion of data from a single ten-hour survey improves tidal predictions, as verified with independent data. Furthermore, the posterior penalty functional is shown to be an effective test statistic for the existence of nontidal flow. The inverse model reduces model-data misfit, using interior dynamics and open-boundary conditions as weak constraints. Model-data misfit can also be reduced by tuning the friction parameter in the prior tidal model. However, in contrast with inversion, tuning degrades predictability

Comparison of the Anticoagulant Response of a Novel Fluorogenic Anti-FXa Assay wth Two Commercial Anti-FXa Chromogenic Assays

Introduction: Fast and accurate monitoring is crucial in the successful regulation of coagulation therapy. For the treatment of venous thromboembolism, both unfractionated heparin (UFH) and low molecular weight heparins (LMWH) are commonly administered. The chromogenic anti-factor Xa (FXa) assay is currently considered the ‘gold standard’ assay for monitoring LMWH. However different commercial chromogenic methods often differ when tested with the same samples. Fluorogenic anti-FXa assays have the potential to offer greater benefits over chromogenic assays in terms of greater specificity, sensitivity and they are not so influenced by sample opacity or turbidity. Materials and Methods: Commercial plasmas were spiked with pharmacologically relevant concentrations (0–1 U/ml) of UFH, enoxaparin, and tinzaparin. The fluorogenic assay was carried out using previously optimized concentrations of 4 nM FXa and 0.9 μM fluorogenic substrate, in addition to 6.25 μl of 100 mM CaCl2 and 43.75 μl of plasma. The Biophen® and Coamatic chromogenic assays were carried out according to the manufacturer’s instructions. Reaction rates and endpoint values were analyzed and statistical analysis by means of one-way analysis of variance (ANOVA) was performed. Results: The fluorogenic anti-FXa assay was found to have the broadest therapeutic range of 0-1 U/ml with CVs of \u3c 5% for UFH and tinzaparin and CVs \u3c 9% for enoxaparin. Despite their limited measuring range, excellent reproducibility was observed with both chromogenic assays Conclusions: This study indicated that the fluorogenic assay is the most sensitive assay with the broadest dynamic range for monitoring LMWH therapy when compared with standard chromogenic assays

Zika Virus-Specific IgY Results Are Therapeutic Following a Lethal Zika Virus Challenge without Inducing Antibody-Dependent Enhancement

The Zika virus (ZIKV) is a newly emerged pathogen in the Western hemisphere. It was declared a global health emergency by the World Health Organization in 2016. There have been 223,477 confirmed cases, including 3720 congenital syndrome cases since 2015. ZIKV infection symptoms range from asymptomatic to Gullain–Barré syndrome and extensive neuropathology in infected fetuses. Passive and active vaccines have been unsuccessful in the protection from or the treatment of flaviviral infections due to antibody-dependent enhancement (ADE). ADE causes an increased viral load due to an increased monocyte opsonization by non-neutralizing, low-avidity antibodies from a previous dengue virus (DENV) infection or from a previous exposure to ZIKV. We have previously demonstrated that polyclonal avian IgY generated against whole-killed DENV-2 ameliorates DENV infection in mice while not inducing ADE. This is likely due to the inability of the Fc portion of IgY to bind to mammalian Fc receptors. We have shown here that ZIKV oligoclonal IgY is able to neutralize the virus in vitro and in IFNAR−/− mice. The concentration of ZIKV-specific IgY yielding 50% neutralization (NT50) was 25 µg/mL. The exposure of the ZIKV, prior to culture with ZIKV-specific IgY or 4G2 flavivirus-enveloped IgG, demonstrated that the ZIKV-specific IgY does not induce ADE. ZIKV IgY was protective in vivo when administered following a lethal ZIKV challenge in 3-week-old IFNAR−/− mice. We propose polyclonal ZIKV-specific IgY may provide a viable passive immunotherapy for a ZIKV infection without inducing ADE

Public Awareness of the Nebraska Regional Poison Control Center

A Poison Control Center needs to continually update its impact on the community it serves. At the Nebraska Regional Poison Control Center, a telephone survey was performed to ascertain baseline data for ongoing poison awareness programs. Our data shows that 36.6% of the population would call the PCC in the case of acute poisoning. There is a need to stress that the PCC is not only a center for information but also for treatment at home. Distribution of the PCC phone number to be attached to the phone needs to be increased. Many people obtained the phone number through time consuming methods which would increase the anxiety of the caller. Despite past programs, 63.9% of the respondents were not familiar with Syrup of Ipecac, and overall out of 608, people, 91.1% did not have Syrup of Ipecac at home in case of poisoning. In distributing poison information to the public, the pre-school and other school programs seem to be very effective. Newspapers and television also are an integral part in distributing poison information. With the help of the networks and newspapers in devoting time and space to poison prevention more households can be reached. There is a need to involve the pharmacist in distribution of poison information. Being the major supplier of Syrup of Ipecac, pharmacists can take a more active role by always carrying Syrup of Ipecac, and displaying it so that patrons may be reminded that they should have it at home

Enhanced VWF clearance in low VWF pathogenesis: Limitations of the VWFpp/VWF:Ag ratio and clinical significance

Increased von Willebrand factor (VWF) clearance plays a key role in the pathogenesis of type 1 and type 2 von Willebrand disease (VWD). However, the pathological mechanisms involved in patients with mild to moderate reductions in plasma VWF:Ag (range, 30-50 IU/dL; low VWF) remain poorly understood. In this study, we investigated the hypothesis that enhanced VWF clearance may contribute to the pathobiology of low VWF. Patients with low VWF were recruited to the LoVIC study after ethics approval and receipt of informed consent. Desmopressin was administered IV in 75 patients, and blood samples were drawn at baseline and at the 1-hour and 4-hour time points. As defined by recent ASH/ISTH/NHF/WFH guidelines, 20% of our low-VWF cohort demonstrated significantly enhanced VWF clearance. Importantly, from a clinical perspective, this enhanced VWF clearance was seen after desmopressin infusion, but did not affect the steady-state VWF propeptide (VWFpp)-to-VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) in most cases. The discrepancy between the VWFpp/VWF:Ag ratio and desmopressin fall-off rates in patients with mild quantitative VWD may have reflected alteration in VWFpp clearance kinetics. Finally, bleeding scores were significantly lower in patients with low VWF with enhanced VWF clearance, compared with those in whom reduced VWF biosynthesis represented the principle pathogenic mechanism. This trial was registered at http://www.clinicaltrials.gov as #NCT03167320

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Recommendations for effective documentation in regional anesthesia: an expert panel Delphi consensus project

Background and objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. Results: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. Conclusion: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia

Economies of Scale and the Atlantic City Casino Industry

Research has produced mixed results regarding the presence of economies of scale in the US casino industry. This study replicated and extended two previous studies (Gu, 2001: Marfels, 1995) that examined economies of scale among Atlantic City casinos. Results were mixed. Depending on how size was operationalized there either was or wasn’t evidence supporting scale economies in Atlantic City. These results have implications for future development in Atlantic City suggesting that management processes may be more important in achieving economies of scale than is the simple physical size of the casino floor

Comparative Study of Factor Xa Fluorogenic Substrates and Their Influence on the Quantification of LMWHs

Low molecular weight heparins (LMWHs) are recognised as the preferred anticoagulants in the prevention and treatment of venous thromboembolism. Anti-Factor Xa (anti-FXa) levels are used to monitor the anticoagulant effect of LMWHs and such assays are routinely employed in hospital diagnostic laboratories. In this study, a fluorogenic anti-FXa assay was developed using a commercially available fluorogenic substrate with an attached 6-amino-1- naphthalene-sulfonamide (ANSN) fluorophore and was used for the determination of two LMWHs, enoxaparin and tinzaparin and the heparinoid, danaparoid. The assay was based on the complexation of heparinised plasma with 100 nM exogenous FXa and 25 μM of the fluorogenic substrate Mes-D-LGR-ANSN (C2H5)2 (SN-7). The assay was tested with pooled plasma samples spiked with anticoagulant concentrations in the range 0–1.6 U mL−1. The statistically sensitive assay range was 0–0.4 U mL−1 for enoxaparin and tinzaparin and 0–0.2 U mL−1 for danaparoid, with assay variation typically below 10.5%. This assay was then compared with a previously published fluorogenic anti- FXa assay developed with the peptide substrate, methylsulfonyl-D-cyclohexylalanyl-glycyl-arginine-7-amino- 4-methylcoumarin acetate (Pefafluor FXa). Both assays were compared in terms of fluorescence intensity, lag times and sensitivity to anticoagulants

Comparison of a Novel Fluorogenic Anti-FXa Assay with a Central Laboratory Chromogenic Anti-FXa Assay for Measuring LMWH Activity in Patient Plasmas

Introduction: Low molecular weight heparins (LMWHs) are used worldwide for the treatment and prophylaxis of thromboembolic disorders. Routine laboratory tests are not required due to the predictable pharmacokinetics of LMWHs, with the exception of pregnant patients, children, patients with renal failure, morbid obesity, or advanced age. Anti-Factor Xa (anti-FXa) plasma levels are most often employed in the assessment and guidance of accurate dosing in these patient cohorts. Materials and methods: A LMWH calibration curve was generated using citrated human pooled plasma spiked with pharmacologically relevant concentrations (0–1 U/ml) of two low molecular weight heparins; enoxaparin and tinzaparin. Least squares analysis determined the best curve fit for this set of data which returned low sum of squares (SS) values for the log linear fit with an R2 value of 0.995. Patient sample concentrations for the fluorogenic anti- FXa assay were determined using the log linear regression equation and correlated with the values reported by the hospital’s standard chromogenic assay. Results: A statistically significant correlation was found between the fluorogenic and the chromogenic anti-FXa assays for 10 patient samples, with a slope of 0.936, offset of 0.228 and an R2 of 0.71 (