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The Vaccine Safety Datalink (VSD) conducts active surveillance and vaccine safety research studies. Since the start of the U.S. COVID-19 vaccination program, the VSD has conducted near real-time safety surveillance of COVID-19 vaccines using Rapid Cycle Analysis. VSD investigators developed an internal dashboard to facilitate visualization and rapid reviews of large weekly automated vaccine safety surveillance data. Dashboard development and maintenance was informed by vaccine surveillance data users and vaccine safety partners. Key metrics include population demographics, vaccine uptake, pre-specified safety outcomes, sequential analyses results, and descriptive data on potential vaccine safety signals. Dashboard visualizations are used to provide situational awareness on dynamic vaccination coverage and the status of multiple safety analyses conducted among the VSD population. This report describes the development and implementation of the internal VSD COVID-19 Vaccine Dashboard, including metrics used to develop the dashboard, which may have application across various other public health settings.

Aminoglycosides are commonly used to treat infections in CF patients and are highly ototoxic. The incidence of tobramycin-induced hearing loss, tinnitus, vertigo or dizziness (ototoxicity) varies widely from 0 to 56% secondary to variation in patient enrollment, dosing, audiometry, and ototoxic criteria. The aim of this study is to determine the incidence of ototoxicity after one course of once-daily IV tobramycin in CF patients. Adult CF patients with acute pulmonary exacerbations were enrolled on IV tobramycin (10 mg/kg/d, ≥10 days). Pure-tone audiometry was performed for standard and extended high frequencies in the sensitive range for ototoxicity (SRO). American-Speech-Language-Hearing-Association cochleotoxicity criteria were applied. Distortion product otoacoustic emissions (DPOAE) and the words-in-noise-test (WINT) were assessed. Tinnitus Functional Index (TFI) and Vertigo Symptoms Scale (VSS) were used. Eighteen CF patients, mean age 31.1 (18–59), were enrolled. The incidence of cochleotoxic change from baseline at 2 and 4 weeks post-treatment was 89% and 93%. For DPOAE, a measure of outer hair-cell function, the incidence of ≥5 dB decrease was 82% and 80%. For WINT, a measure of word recognition, the incidence of ≥10% decrease was 17% and 40%. For TFI, the incidence of ≥10pt increase was 12% and 8%, and for VSS, the incidence of ≥6pt increase was 0% and 8%. One course of IV tobramycin was sufficient to cause hearing loss and other ototoxic symptoms four weeks after treatment ended. Audiometric measures were more sensitive to ototoxic change than TFI & VSS. Age and duration of tobramycin treatment were not obvious factors for predicting ototoxicity.

Aims Seventy percent of Africans living with diabetes are undiagnosed. Identifying who should be referred for testing is critical. Therefore we evaluated the ability of the Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation with A1C added (ARIC + A1C) to identify diabetes in 451 African-born blacks living in America (66% male; age 38 ± 10y (mean ± SD); BMI 27.5 ± 4.4 kg/m2). Methods All participants denied a history of diabetes. OGTTs were performed. Diabetes diagnosis required 2-h glucose ≥200 mg/dL. The five non-invasive (Age, parent history of diabetes, waist circumference, height, systolic blood pressure) and four invasive variables (Fasting glucose (FPG), A1C, triglycerides (TG), HDL) were obtained. Four models were tested: Model-1: Full ARIC + A1C equation; Model-2: All five non-invasive variables with one invasive variable excluded at a time; Model-3: All five non-invasive variables with one invasive variable included at a time; Model-4: Each invasive variable singly. Area under the receiver operator characteristic curve (AROC) predicted diabetes. Youden Index identified optimal cut-points. Results Diabetes occurred in 7% (30/451). Model-1, the full ARIC + A1C equation, AROC = 0.83. Model-2: With FPG excluded, AROC = 0.77 (P = 0.038), but when A1C, HDL or TG were excluded AROC remained unchanged. Model-3 with all non-invasive variables and FPG alone, AROC=0.87; but with A1C, TG or HDL included AROC declined to ≤0.76. Model-4: FPG as a single predictor, AROC = 0.87. A1C, TG, or HDL as single predictors all had AROC ≤ 0.74. Optimal cut-point for FPG was 100 mg/dL. Conclusions To detect diabetes, FPG performed as well as the nine-variable updated ARIC + A1C equation.

Horizontally-oriented echosounders have become more common for sampling pelagic prey species in shallow waterbodies (e.g.

Objective Evidence-based strategies to address vaccine hesitancy are lacking. Personal values are a measurable psychological construct that could be used to deliver personalized messages to influence vaccine hesitancy and behavior. Our objectives were to develop a valid, reliable self-report survey instrument to measure vaccine values based on the Schwartz theory of basic human values, and to test the hypothesis that vaccine values are distinct from vaccine attitudes and are related to vaccine hesitancy and behavior. Methods Parental Vaccine Values (PVV) scale items were generated using formative qualitative research and expert input, yielding 24 items for testing. 295 parents of children aged 14–30 months completed a self-report survey with measures of Schwartz’s global values, the PVV, vaccine attitudes, and vaccine hesitancy. Factor analysis was used to determine vaccine values factor structure. Associations between vaccine values, vaccine attitudes, vaccine hesitancy, and vaccination behavior were assessed using linear and logistic regression models. Late vaccination was assessed from electronic medical records. Results A six-factor structure for vaccine values was determined with good fit (RMSEA = 0.07, Bentler’s CFI = 0.91) with subscales for Conformity, Universalism, Tradition, Self-Direction, Security- Disease Prevention, and Security- Vaccine Risk. Vaccine values were moderately associated with Schwartz global values and vaccine attitudes, indicating discriminant validity from these constructs. Multivariable linear regression showed vaccine hesitancy was associated with vaccine values Conformity (partial R2 = 0.10) and Universalism (0.04) and vaccine attitudes Vaccine Safety (0.52) and Vaccine Benefit (0.16). Multivariable logistic regression showed that late vaccination was associated with vaccine value Self-direction (OR = 1.80, 95% CI: 1.26–2.65) and vaccine attitude of Vaccine Benefit (OR = 0.44, 95% CI: 0.32–0.60). Conclusions The PVV scale had good psychometric properties and appears related to but distinct from Schwartz global values and vaccine attitudes. Vaccine values are associated with vaccine hesitancy and late vaccination and may be useful in tailoring future interventions.

Recently [11C]mG4P012 (previously [11C]KALB012 and presently named as [11C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and l -dopa-induced dyskinesia. [11C]mG4P012 was shown to be a promising PET radioligand for mGluR4 in the monkey brain and for further development in human subjects. However, the previously reported multi-step synthesis of the thiophenol precursor suffered from low yields and difficult workup procedures. To support the translational research of [11C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.

Prey-density data are often used when making management decisions for piscivorous fish species (i.e. stocking rates). Gizzard Shad (Dorosoma cepedianum) are an important prey species in lakes and reservoirs throughout much of the United States. Currently, gill nets are the most common gear used to collect Gizzard Shad data used for deriving population characteristics, but this gear can be time and labor intensive, lacks precision, and may lack accuracy. Horizontally-oriented echosounders may be a better alternative, but accuracy and precision must be measured to determine if this sampling technique produces reliable data. We released Gizzard Shad into a net pen (15-m long × 15-m wide × 4.5-m deep with 6.35-mm square mesh) to produce several different densities of fish. Mean densities were estimated using five passes with a Simrad® EK60 120 kHz split-beam echosounder. Density estimates were acquired by echo-counting and echo-integration. Mean density estimates were then compared to known densities using a linear mixed-effects model and relative standard error (RSE) was calculated for each trial from the five sampling passes. Both echo-counting and echo-integration had slopes not significantly different from one (t = 0.82, d.f. = 13, P = 0.33; t = 3.58, d.f. = 13, P = 0.55) but intercepts that were significantly greater than zero (t = 2.89, d.f. = 88, P

Performance period or life span of a flexible pavement is dependent upon the load carrying capacity of its base and subbase layers. Pavement strength characteristics influenced by material properties of these foundation layers are of utmost importance in the pavement design. In this experimental study, the goal was to adequately define the limits of different unbound aggregate properties influencing the strength of unbound aggregate. Material type, gradation, maximum particle size, fines content, dust ratio and plasticity index were among the different properties studied. Dust ratio is defined as the ratio of material passing the No. 200 sieve (i.e. fines content) to material passing the No. 40 sieve. As for the aggregate materials, crushed limestone and crushed gravel, commonly used in Illinois in base/subbase applications, were considered. Illinois dense graded base specifications allow aggregate materials with a maximum particle size of 25 mm for the CA 6 specification and 50 mm maximum particle size for the CA 2 aggregate. Plasticity index, fines content, and dust ratio ranged from 5% to 13%, 5% to 12%, and 0.4 to 1.0, respectively. California Bearing Ratio (CBR) and staged triaxial tests were performed to characterize the material strength. Higher strength values were obtained for the CA 6 aggregates with 25-mm maximum particle size compared to the aggregates tested for CA 2 specification. Considering typical property ranges, a dust ratio of 1.0 was found to be a viable option in some cases for base/subbase applications providing an acceptable soaked strength for both crushed limestone and crushed gravel. However, for both material types, the combination of a dust ratio of 0.4 and a fines content of 12% posed a severe negative effect on aggregate strength.

Objectives Some parents are concerned the childhood immunization schedule could increase risk for allergic disorders, including asthma. To inform future safety studies of this speculated association, a parent survey was conducted to examine the risk of misclassification of vaccination status in electronic health record data, and to assess the potential for confounding if asthma risk factors varied by vaccination status. Methods A survey was conducted among parents of children 19 to 35 months old at 6 medical organizations within the Vaccine Safety Datalink. Parents of children in 4 vaccination groups were surveyed: 1) no vaccines by 12 months of age and a diagnosis of parental vaccine refusal; 2) consistent vaccine limiting (≤2 vaccines per visit); 3) not consistently vaccine limiting but otherwise undervaccinated with a vaccine refusal diagnosis; and 4) fully vaccinated with no delays and no vaccine refusal. Parents were surveyed about their child's vaccination status and whether asthma risk factors existed. Results Among a survey sample of 2043 parents, 1209 responded (59.2%). For receiving no vaccines, the observed agreement between parent report and electronic health record data was 94.0% (κ = 0.79); for receiving all vaccines with no delays, the observed agreement was 87.3% (κ = 0.73). Although most asthma risk factors (allergic rhinitis, eczema, food allergies, family asthma history) reported by parents did not differ significantly between children in the vaccination groups studied, several factors (aeroallergen sensitivity, breastfeeding) differed significantly between groups. Conclusions Measurement and control of disease risk factors should be carefully considered in observational studies of the safety of the immunization schedule.

Introduction Successful strategies are needed to address parental vaccine hesitancy, a significant public health issue. The study objective was to assess whether an Internet-based platform with vaccine information and interactive social media components improved parents’ vaccine-related attitudes. Study design A three-arm RCT. Setting/participants The study was conducted in a large Colorado integrated healthcare organization. Parents were enrolled during September 2013 through October 2015 and followed through November 2016; data were analyzed in 2017. Parents, recruited during pregnancy, were given a survey about vaccine-related attitudes at enrollment (i.e., baseline) and when their child was aged 3–5 months and 12–15 months (Timepoints 1 and 2, respectively). Parental vaccine hesitancy was assessed at baseline. Intervention Study participants were randomized to the following: a study website with vaccine information and social media components (VSM arm); a website with vaccine information only (VI); or usual care. Main outcome measures Change in parental vaccine attitudes over time by baseline degree of vaccine hesitancy. Results Among 1,093 study participants, 945 (86.5%) completed all three surveys. Comparing baseline with Timepoint 1 among vaccine-hesitant parents, the VSM and VI arms were associated with significant improvements in attitudes regarding vaccination benefits compared to usual care (VSM mean change 0.23 on a 5-point scale, 95% CI=0.05, 0.40, VI mean change 0.22, 95% CI=0.04, 0.40). Comparing baseline with Timepoint 2 among hesitant parents, the VSM and VI arms were also associated with significant reductions in parental concerns about vaccination risks compared to usual care (VSM mean change –0.37, 95% CI= –0.60, –0.14, VI mean change –0.31, 95% CI= –0.55, –0.07). Self-efficacy around vaccine decision making also improved among vaccine-hesitant parents. No intervention effect was observed among parents not vaccine-hesitant at baseline. Conclusions Among vaccine-hesitant parents, an Internet-based intervention improved parents’ attitudes about vaccines. Trial registration This study was registered at www.clinicaltrials.gov NCT01873040.

Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy has become a common technique to study polymorphism in pharmaceutical solids at high-resolution. However, high-throughput application of high resolution SS-NMR spectroscopy is severely limited by the long 1H spin-lattice relaxation (T1) that is common to solid phase compounds. Here, we demonstrate the use of paramagnetic relaxation reagents such as chromium (III) acetylacetonate (Cr(acac)3) and nickel (II) acetylacetonate (Ni(acac)2) for fast data acquisition by significantly reducing the T1 value for carbamazepine Forms I, II, III, and dihydrate, cimetidine Forms A and B, nabumetone Form I, and acetaminophen Form I polymorphs. High resolution 13C cross-polarization and magic angle spinning were used to measure T1 values for each polymorph. In order to confirm the absence of polymorphic transitions during SS-NMR experiments, powder x-ray diffraction was implemented. The amount of chromium ions incorporated by the recrystallization process was quantified by using inductively coupled plasma optical emission spectroscopy. Our results suggest that the paramagnetic ions added to the polymorphs do not affect the polymorphic transformation or the quality of NMR spectra. We believe that this successful demonstration of fast data collection will enable high-throughput utilization of SS-NMR techniques to study polymorphic solids and could set the groundwork for NMR crystallography studies.

Resilient modulus (Mr) and permanent deformation (PD) characteristics of unbound aggregates under repetitive traffic loads dictate the structural response and performance of pavement base and subbase layers. Aggregate material behavior is dependent on the amount of fines in particulate matrix, also referred to as fines content (percent passing number 200 sieve), as well as plasticity index, dust ratio (percent passing number 200 sieve to percent passing number 40 sieve), material type, aggregate gradation/packing and the interactions of these properties with each other. In this study, repeated load triaxial tests were conducted on crushed limestone and crushed gravel aggregates. Fines content and plasticity index were varied from 5% to 12% and 5% to 9%, respectively. Two most typical gradations of aggregates used in roadway construction in Illinois were utilized with dust ratios ranging from 0.4 to 1.0. The results of these tests were analyzed using the shakedown theory for evaluating typical base/subbase permanent deformation or rutting trends linked to practical design considerations. Charts were also established for the modulus and deformation characteristics of unbound aggregates to designate the material quality with performance trends. Such guiding charts were compared with others developed in previous studies by authors for determining aggregate behavior under monotonic loading tests such as California Bearing Ratio (CBR). The comparisons provide valuable insights on how each aggregate property influences strength, modulus and permanent deformation behavior under different loading conditions.

Spherical polymer shells containing cryogenic DT ice layers have been imploded on the OMEGA Laser System and radiographed using Si backlighter targets (hν = 1.865 keV) driven with 20-ps IR pulses from the OMEGA EP Laser System. We report on a series of implosions in which the deuterium–tritium (DT) shell is imaged for a range of convergence ratios and in-flight aspect ratios. The shadows of the converging DT ice and polymer shells are recorded while the self-emission is minimized using a time-resolved (40-ps) monochromatic crystal imaging system. The images acquired have been analyzed for the level of ablator mixing into the DT fuel (even 0.1% of carbon mix can be reliably inferred). Simulations are compared with measured x-ray radiographs to provide insight into the early time and stagnation stages of an implosion, to guide the modeling efforts to improve the target designs, and to guide the development of this and other imagining techniques, such as Compton radiography.

Proper characterization of a dense-graded aggregate base/subbase material should include both quality and strength aspects. Gradation, passing the No. 200 sieve (smaller than 0.075 mm) fines content, and Atterberg limits for plasticity index (PI) are the most important properties that affect the quality and longevity of aggregates used as unbound layers in flexible pavement applications. The criterion used for allowing fines in high quality aggregates for highway applications vary among the state agencies. Most specifications call for controlling fines content, PI and the dust ratio, which is defined as percent passing the No. 200 sieve divided by percent passing the No. 40 sieve. In this study the effect of these fines on moisture-density relationship and strength of a crushed limestone aggregate with 25.4-mm (1-in.) maximum particle size was investigated. A typical range of 5–12% fines content inclusion with plasticity indices of 5–13% and dust ratios of 0.4–1.0 were studied. In order to evaluate the influence of each of these properties of the fines, a comprehensive number of samples were tested for the soaked California Bearing Ratio (CBR). The moisture sensitivity of aggregate strength was evaluated within ±1.5% of the optimum moisture content. The findings were summarized to propose a new approach for proper material selection based on the fines content and dust ratio.

Tandem hoop nets have become the primary gear for sampling channel catfish Ictalurus punctatus, but suffer from high incidences of bycatch, particularly aquatic turtles that usually drown as a result. We sought to determine if bait type, ZOTE© soap and ground cheese logs, would influence catch of channel catfish (CPUE and mean TL) and bycatch of fishes and aquatic turtles. We sampled with tandem hoop nets in 13 Kentucky reservoirs (5–73 ha) using a crossover design and two sampling events. We found no difference in channel catfish catch rates between bait types, but mean sizes of fish caught using ZOTE© soap were approximately 24 mm longer compared to cheese. Fish bycatch was similar between bait types, but tandem hoop nets baited with ZOTE© soap caught up to 61% fewer turtles and mortality of turtles that were captured was up to 12% lower than those baited with cheese. Depth of net set, water temperature, and Secchi depth were environmental factors measured that affected catch and bycatch, but varied among species. Using ZOTE© soap as bait in tandem hoop nets appears to be a fairly simple and straightforward method for maintaining high catch rates of channel catfish while minimizing turtle mortality.

Human cytomegalovirus (HCMV) infects up to 90–100% of the world population. Although HCMV infection is not a concern for immunocompetent patients, it can be life threatening for immunocompromised individuals. Additionally, congenital HCMV infections can cause serious neurological deficits in neonates. Since viral resistance mutations arise for all current treatments, new treatments targeting novel processes are needed. A well-defined target for HCMV is heparan sulfate, a highly sulfated glycosaminoglycan (GAG) necessary for virion/host cell attachment. In this study, we investigated as possible antiviral agents substitution-inert cationic polynuclear platinum complexes (PPCs) that demonstrate charge-dependent high affinity for GAGs (Katner et al., 2018; Peterson et al., 2017). Certain PPCs had anti-HCMV activities in low micromolar concentrations and antiviral activity correlated with their GAG-binding affinity. Time of addition, removal, and mechanistic studies were consistent with PPCs binding to cells and blocking HCMV virion attachment; however, evidence also suggested that PPC/virion interactions could inhibit fibroblast but not epithelial cell infection. We hypothesize that the PPC-heparan sulfate interaction described here is a general approach to inhibition of virion/host cell attachment and viral entry mediated by other anionic GAGs and sialic acids on the cell surface. Through metalloshielding of the critical sulfate receptors, PPCs offer an attractive alternative to current antiviral compounds, with the potential to target a broad spectrum of viruses that utilize GAGs for attachment and entry.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS :A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006—June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Since 2013, after Utah became the first state to implement hearing targeted early CMV screening, a national debate has been percolating about whether this approach should be introduced nationally. Currently Utah, Iowa, Connecticut, and New York have passed legislation mandating early CMV screening, and over 100 birth hospitals across the United States have voluntarily implemented early CMV screening programs as part of their standard of care. We reviewed the evidence related to this approach and used the Wilson and Jungner (1968) criteria to evaluate this method of screening. Based on these criteria, there is substantial rationale and evidence to support a hearing targeted approach to screen for congenital CMV. Given this evidence, we currently recommend that infants who fail newborn hearing screen should undergo CMV screening.