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25 result(s) for "McClellan, Jessica"
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Prozone masks elevated SARS-CoV-2 antibody level measurements
We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program. In July, 2022, samples were collected from ten participants with anomalously low results for serial dilution studies, and a prozone effect was confirmed. From October, 2022 to March, 2023, serial dilution of samples detected 74 additional cases of prozone out of 1,720 participants’ samples. Prozone effect may affect clinical management of at-risk populations repeatedly exposed to SARS-CoV-2 spike protein through multiple immunizations or serial infections, making awareness and mitigation of this issue paramount.
Vital Directions For Health And Health Care: Priorities For 2021
In 2016, in anticipation of the US presidential election and forthcoming new administration, the National Academy of Medicine launched a strategic initiative to marshal expert guidance on pressing health and health care priorities. Published as Vital Directions for Health and Health care, the products of the initiative provide trusted, nonpartisan, evidence-based analysis of critical issues in health, health care, and biomedical science. The current collection of articles published in Health Affairs builds on the initial Vital Directions series by addressing a set of issues that have a particularly compelling need for attention from the next administration: health costs and financing, early childhood and maternal health, mental health and addiction, better health and health care for older adults, and infectious disease threats. The articles also reflect the current experience with both the coronavirus disease 2019 (COVID-19) pandemic and the health inequities that have been drawn out sharply by COVID-19, as well as the implications going forward for action.
Biomechanical Analysis of Revision Strategies for Rod Fracture in Pedicle Subtraction Osteotomy
Abstract BACKGROUND: Pseudoarthrosis after pedicle subtraction osteotomy (PSO) can require revision surgery due to posterior rod failure, and the stiffness of these revision constructs has not been quantified. OBJECTIVE: To compare the multidirectional bending stiffness of 7 revision strategies following rod failure. METHODS: Seven fresh-frozen human spines (T11-pelvis) were tested as follows: (1) posterior instrumentation from T12-S1 (excluding L3) with iliac fixation and L3 PSO; (2) inline connectors after rod breakage at L3 (L2 screws removed for access); (3) cross-links connecting rods above and below inline connectors; satellite rods (4) parallel, (5) 45° anterior, and (6) 45° posterior to original rods; 45°posterior with cross-links connecting (7) original and (8) satellite rods. Groups 3 to 8 were tested in random order. Nondestructive pure moment flexion-extension (FE), lateral bending (LB), and axial rotation (AR) tests were conducted to 7.5 Nm; 3D motion tracking monitored the primary range of motion. RESULTS: Addition of inline connectors alone restored stiffness in FE and LB (P > .05), but not in AR (P < .05). Satellite rods (groups 4 to 6) restored stiffness in FE and LB (P > .05), but not in AR (P < .05) and were not significantly different from one another (P > .05). The addition of cross-links (groups 3, 7, and 8) restored stiffness in all bending modes (P > .05) and were significantly greater than inline connectors alone in AR (P < .05). CONCLUSION: The results suggest that these revision strategies can restore stiffness without entire rod replacement. Failure of AR stiffness restoration can be mitigated with cross-links. The positioning of the satellite rods is not an important factor in strengthening the revision.
Spinal Cord Injury Significantly Alters the Properties of Reticulospinal Neurons: I. Biophysical Properties, Firing Patterns, Excitability, and Synaptic Inputs
Following spinal cord injury (SCI) for larval lampreys, descending axons of reticulospinal (RS) neurons regenerate, and locomotor function gradually recovers. In the present study, the electrophysiological properties of uninjured (left)-injured (right) pairs of large, identified RS neurons were compared following rostral, right spinal cord hemi-transections (HTs). First, changes in firing patterns of injured RS neurons began in as little as 2–3 days following injury, these changes were maximal at ~2–3 weeks (wks), and by 12–16 wks normal firing patterns were restored for the majority of neurons. Second, at ~2–3 wks following spinal cord HTs, injured RS neurons displayed several significant changes in properties compared to uninjured neurons: (a) more hyperpolarized VREST; (b) longer membrane time constant and larger membrane capacitance; (c) increased voltage and current thresholds for action potentials (APs); (d) larger amplitudes and durations for APs; (e) higher slope for the repolarizing phase of APs; (f) virtual absence of some afterpotential components, including the slow afterhyperpolarization (sAHP); (g) altered, injury-type firing patterns; and (h) reduced average and peak firing (spiking) frequencies during applied depolarizing currents. These altered properties, referred to as the “injury phenotype”, reduced excitability and spiking frequencies of injured RS neurons compared to uninjured neurons. Third, artificially injecting a current to add a sAHP waveform following APs for injured neurons or removing the sAHP following APs for uninjured neurons did not convert these neurons to normal firing patterns or injury-type firing patterns, respectively. Fourth, trigeminal sensory-evoked synaptic responses recorded from uninjured and injured pairs of RS neurons were not significantly different. Following SCI, injured lamprey RS neurons displayed several dramatic changes in their biophysical properties that are expected to reduce calcium influx and provide supportive intracellular conditions for axonal regeneration.
Using clinical decision support to improve urine testing and antibiotic utilization
Urine cultures collected from catheterized patients have a high likelihood of false-positive results due to colonization. We examined the impact of a clinical decision support (CDS) tool that includes catheter information on test utilization and patient-level outcomes. This before-and-after intervention study was conducted at 3 hospitals in North Carolina. In March 2021, a CDS tool was incorporated into urine-culture order entry in the electronic health record, providing education about indications for culture and suggesting catheter removal or exchange prior to specimen collection for catheters present >7 days. We used an interrupted time-series analysis with Poisson regression to evaluate the impact of CDS implementation on utilization of urinalyses and urine cultures, antibiotic use, and other outcomes during the pre- and postintervention periods. The CDS tool was prompted in 38,361 instances of urine cultures ordered in all patients, including 2,133 catheterized patients during the postintervention study period. There was significant decrease in urine culture orders (1.4% decrease per month; < .001) and antibiotic use for UTI indications (2.3% decrease per month; = .006), but there was no significant decline in CAUTI rates in the postintervention period. Clinicians opted for urinary catheter removal in 183 (8.5%) instances. Evaluation of the safety reporting system revealed no apparent increase in safety events related to catheter removal or reinsertion. CDS tools can aid in optimizing urine culture collection practices and can serve as a reminder for removal or exchange of long-term indwelling urinary catheters at the time of urine-culture collection.
A pilot study of disulfiram for individuals with persistent symptoms despite prior antibiotic treatment for Lyme disease
studies report that disulfiram is effective in killing . Case series suggest disulfiram may help to reduce the symptoms of patients with persistent symptoms despite prior antibiotic treatment for Lyme disease. This pilot study assessed safety, tolerability, and signs of clinical response. Participants with a history of previously treated Lyme disease and persistent fatigue were randomly assigned in a double-blinded fashion to either Group A (disulfiram for 4 weeks and placebo for 4 weeks) or Group B (disulfiram for 8 weeks). Primary outcome endpoint was at 10 weeks with a follow-up at 14 weeks. The primary aim was to assess safety and tolerability. A clinical aim assessed signs of clinical improvement using well-validated measures, focusing on improvement in fatigue and quality of life. Target enrollment was 24 participants. 940 individuals were screened, 11 were enrolled and nine participated in the trial. Dosing started low and increased based on response and tolerance to a maximum of 500 mg daily. Safety. Two participants discontinued medication due to clinical worsening, one of whom was briefly hospitalized. Three additional participants were withdrawn from treatment due to lab test abnormalities. Tolerability. Only three of nine participants completed the full course of treatment (two in Group A and one in Group B). Lower doses were better tolerated than the highest dose. Clinical response. Of nine participants, clinically meaningful improvement was noted in fatigue for six and in quality of life for four. Among the six fatigue responders, improvement was also noted on a multiple domain symptom index (six of six), overall symptom burden (five of six), and functional impairment (four of six). The study was terminated early due to end of project funding, higher than expected adverse events, and recognition that sufficient information was gathered to inform future studies. This study reveals the risks associated with disulfiram, especially at higher doses, while suggesting potential clinical benefits among some participants. Efficacy could not be assessed given the small sample size and the lack of a placebo-control group. https://clinicaltrials.gov/study/NCT03891667?cond=Lyme%20Disease&intr=disulfiram&rank=1, NCT03891667.
Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications
Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions and duplications are associated with neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying the same computerized neurocognitive assessment, the Penn Computerized Neurocognitive Battery (CNB), administered in a multi-site study on rare genomic disorders: 22q11.2 deletions ( n  = 492); 22q11.2 duplications ( n  = 106); 16p11.2 deletion ( n  = 117); and 16p11.2 duplications ( n  = 46). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and psychomotor speed. Accuracy and speed for each domain were included as dependent measures in a mixed-model repeated measures analysis. Locus (22q11.2, 16p11.2) and Copy number (deletion/duplication) were grouping factors and Measure (accuracy, speed) and neurocognitive domain were repeated measures factors, with Sex and Site as covariates. We also examined correlation with IQ. We found a significant Locus × Copy number × Domain × Measure interaction ( p  = 0.0004). 22q11.2 deletions were associated with greater performance accuracy deficits than 22q11.2 duplications, while 16p11.2 duplications were associated with greater specific deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed compared to deletions. Performance profiles differed among the groups with particularly poor memory performance of the 22q11.2 deletion group while the 16p11.2 duplication group had greatest deficits in complex cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. Deletions and duplications of 22q11.2 and 16p11.2 have differential effects on accuracy and speed of neurocognition indicating locus specificity of performance profiles. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome, and can only be established in large-scale international consortia using the same neurocognitive assessment. Future studies could aim to link performance profiles to clinical features and brain function.
Seedling growth rate and root traits in the maize Nested Association Mapping (NAM) panel
This paper characterizes variation in shoot and root traits collected from the founders of the Maize Nested Association Mapping panel, which was designed to maximize genetic diversity while ensuring appropriate flowering in eastern North America. Here, we present a detailed account of greenhouse experiments conducted by four cohorts of undergraduate research interns at the University of Hawaiʻi at Mānoa. We summarize data collection, data cleaning procedures, and present data for 38 phenotypic variables for 24 genotypes with the number of plant replicates ranging from 3 to 20. The genotype B73 served as our experimental control to enable comparison over the four years. We also grew a subset of genotypes under different abiotic stress treatments to assess the phenotypic plasticity. These data can be used to predict the potential for different lines to function and capacity to adapt to different environments. Data are published on GitHub repositories, and have large reuse potential by the scientific community, as well as educators of undergraduate and graduate instruction.