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Biomedical subjects

R Ball

Publications and source records attributed to R Ball.

At least 19 recordsLinked to original sources

Comparison of military and civilian reporting rates for smallpox vaccine adverse events.

INTRODUCTION: US smallpox vaccination (SMA) started most recently in December 2002. Military and civilian personnel report adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS), a surveillance system that relies on spontaneous reports. Although reported rates of probable myo/pericarditis after SMA in the literature are similar between military personnel and civilian healthcare workers, some civilian AE reporting rates after SMA appeared higher than those in the military. OBJECTIVE: Determine if SMA-associated reporting rates are different in civilians than in the military, considering age, sex, seriousness, and expectedness of the AE, as well as self-reporting. METHODS: Numerators were SMA reports in VAERS from 12/12/02 to 3/1/04. Limitations of VAERS include underreporting and lack of diagnostic confirmation. Denominators were number of military and civilian vaccinees. RESULTS: Reporting rates stratified by age and sex of serious and non-serious AEs were significantly higher in civilian than military personnel ages <55 years (rate ratios 4-27). These rate ratios decreased with increasing age. CONCLUSIONS: Reporting rates in VAERS differed significantly and substantially in civilians compared to military personnel <55 years of age. Differences in stimulated passive surveillance systems, and AE reporting practices, including the 'threshold' for reporting most likely explain these findings. These results suggest that in the case of smallpox vaccine AEs, there may be systematic differences in reporting completeness between the civilian and military sectors, and that passive surveillance data should be interpreted with caution.

Adult↗

Inheritance of time to flowering in chickpea in a short-season temperate environment.

Time to flowering is central in determining the adaptation and productivity of chickpea in short-season temperate environments. We studied the genetic control of this trait in three crosses, 272-2 x CDC Anna, 298T-9 x CDC Anna, and 298T-9 x CDC Frontier. From each cross, 180 F2 plants and parents were evaluated for time to flowering under greenhouse conditions. In summer 2004, multiple generations including P1, F1, P2, F2, and F2:3 (also called MG5) were evaluated for time to flowering under field conditions. The data on time to flowering in the F(2) populations were continuous in distribution but deviated from normal distribution. The F2:3 families derived from this showed a bimodal distribution for time to flowering, a typical case of major-gene inheritance model with duplicate recessive epistasis. A joint segregation analysis of MG5 also revealed that time to flowering in chickpea was controlled by two major genes along with other polygenes. Late flowering was dominant over early flowering for both major genes with digenic interaction between them, mainly an additive x additive type. This information can be used to formulate the most efficient breeding strategy for improvement of time to flowering in chickpea in short-season temperate environments.

Cicer↗

Clinical value of obtaining sputum and cough swab samples following inhaled hypertonic saline in children with cystic fibrosis.

Prompt detection and treatment of lower respiratory tract infection are essential in the management of patients with cystic fibrosis (CF), who often have signs or symptoms of respiratory infection without any pathogens being isolated from sputum or cough swab specimens. The aims of this study were to assess the efficacy and clinical value of obtaining sputum and oropharyngeal cough swab samples following induction with hypertonic saline (HS) in this group of patients. Forty-three outpatients with CF, mean age 7.2 years (range, 1.8-12.9 years), were recruited over a 2-year period. Nebulized salbutamol was administered, followed by 6% HS. Sputum was preferentially obtained before and after HS induction if possible. If the patient was not able to expectorate, oropharyngeal cough swabs were taken instead. Four patients were able to expectorate sputum before and 19 after HS induction. The procedure was tolerated in 41 of 43 patients. Pathogens were isolated from 13 patients' HS-induced samples, but not from their corresponding preinduced specimens, and 4 patients' preinduced specimens cultured organisms which were not identified from their HS-induced samples. Significant changes were made in the management of 13 (30.2%) patients directly resulting from the positive culture of pathogens only from HS-induced samples. Cultures from oropharyngeal cough swab or expectorated sputum specimens following inhalation of HS provide additional microbiological information which is of clinical value and may lead to changes in patient management.

Administration, Inhalation↗

The effect of an imprecise map on interval mapping QTLs.

The statistical analysis of quantitative trait locus (QTL) experiments relies on the use of a linkage map of the markers genotyped. Such a map is, at best, a good estimate of the true map. Resources might be diverted into developing better marker maps or improved maps become available after the analysis, raising concerns over the original analysis. It is therefore important to understand the sensitivity of QTL analysis to map inaccuracy. We have used simulation methods to investigate the consequences of an incorrect map on the results of a QTL analysis using interval mapping. Backcross data sets were generated with a particular map and then analysed with both the correct map and incorrect maps. If the incorrect maps maintained the true linkage groups (i.e. no markers were incorrectly assigned to another linkage group), the accuracy of the map had little or no impact on the ability to detect QTLs, the true significance levels of the tests or the relative placement of QTLs. When a marker was incorrectly placed on another linkage group, there was a small increase in the level of the test. After adjusting for this increase, there was a decrease in power to detect a QTL near the misplaced marker. This decrease was of a similar magnitude to that found when using a single-marker analysis compared with interval mapping. These results mean that QTL analyses can proceed without the need for very accurate marker maps, and that estimated QTL positions can be translated onto updated maps without the need for reanalysis.

Chromosome Mapping↗

Metamorphosis of plasma turbulence-shear-flow dynamics through a transcritical bifurcation.

The structural properties of an economical model for a confined plasma turbulence governor are investigated through bifurcation and stability analyses. A close relationship is demonstrated between the underlying bifurcation framework of the model and typical behavior associated with low- to high-confinement transitions such as shear-flow stabilization of turbulence and oscillatory collective action. In particular, the analysis evinces two types of discontinuous transition that are qualitatively distinct. One involves classical hysteresis, governed by viscous dissipation. The other is intrinsically oscillatory and nonhysteretic, and thus provides a model for the so-called dithering transitions that are frequently observed. This metamorphosis, or transformation, of the system dynamics is an important late side-effect of symmetry breaking, which manifests as an unusual nonsymmetric transcritical bifurcation induced by a significant shear-flow drive.

Journal Article↗

Safety data on meningococcal polysaccharide vaccine from the Vaccine Adverse Event Reporting System.

Recent recommendations by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may lead to the increased use of the meningococcal polysaccharide vaccine. The Vaccine Adverse Event Reporting System (VAERS) is useful for the detection of previously unrecognized reactions and for the monitoring of known reactions. Limitations of VAERS include underreporting and the inability to establish a causal relationship between vaccination and adverse events in most cases. From July 1990 through 31 October 1999, 110 adverse events were reported after receipt of meningococcal vaccine alone. Thirteen (12%) were serious, including 6 injection site reactions, 3 allergic reactions, 1 case of Guillain-Barré syndrome, and 3 miscellaneous events. Fever (30%), headache (17%), dizziness (15%), injection site hypersensitivity (13%), urticaria (12%), and paresthesia (10%) were among the most common events reported. Fever and injection site and allergic reactions are most likely causally linked to the vaccine. That there were few reports of serious adverse events, with >6 million doses having been distributed, and no clear signal of a previously unrecognized serious reaction is reassuring with regard to the safety of meningococcal vaccine.

Consumer Product Safety↗

Strong "quantum" chaos in the global ballooning mode spectrum of three-dimensional plasmas.

The spectrum of ideal magnetohydrodynamic (MHD) pressure-driven (ballooning) modes in strongly nonaxisymmetric toroidal systems is difficult to analyze numerically owing to the singular nature of ideal MHD caused by lack of an inherent scale length. In this paper, ideal MHD is regularized by using a k-space cutoff, making the ray tracing for the WKB ballooning formalism a chaotic Hamiltonian billiard problem. The minimum width of the toroidal Fourier spectrum needed for resolving toroidally localized ballooning modes with a global eigenvalue code is estimated from the Weyl formula. This phase-space-volume estimation method is applied to two stellarator cases.

Journal Article↗

Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women.

Aging is often associated with a dysregulation of the immune system. We examined mitogen-stimulated production of interleukin (IL)-2 and proinflammatory cytokines, IL-1beta and IL-6, in apparently healthy and generally well-nourished old versus young women. Subjects were screened for health using the SENIEUR protocol and a panel of laboratory tests for inflammation, as well as for the adequacy of nutritional status using criteria related to undernutrition, and protein, iron, vitamin B(12), and folate status. Young (n=26, age: 20-40 years) and old (n=44, age: 62-88 years) cohorts did not differ on the number of circulating monocytes, granulocytes, B (CD19+) cells, and T (CD3+, CD4+, and CD8+) cells. No differences (P>0.10) were seen between the two age groups in IL-2, IL-1beta and IL-6 levels in whole blood cultures at 48 h after stimulation with PHA (5 mg/l). Furthermore, no age-related differences were noted in the absolute amounts (pg) of IL-1beta and IL-6 after normalizing for circulating monocytes, B cells, or T cells (P>0.10). Similarly, no age-related decline in absolute amount of IL-2 (pg) after normalizing for circulating T cells was noted (P>0.10). Thus, contrary to most previous reports, our results do not support an increase in the production of proinflammatory cytokines IL-1beta and IL-6, and a reduced production of IL-2 with aging when health and nutritional status are maintained. These findings support our previous results of no change in monocyte function and few alterations in acquired immune response in a carefully selected group of healthy and well-nourished elderly women.

Adult↗

Stevens-Johnson syndrome and toxic epidermal necrolysis after vaccination: reports to the vaccine adverse event reporting system.

We conducted a telephone survey of reports of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) to the Vaccine Adverse Event Reporting System. We identified six cases of SJS or TEN after vaccination without other obvious triggers, suggesting that SJS and TEN might very rarely be caused by vaccination. Confirmation of this hypothesis will likely require controlled studies.

Adult↗

An assessment of thimerosal use in childhood vaccines.

BACKGROUND: On July 7, 1999, the American Academy of Pediatrics and the US Public Health Service issued a joint statement calling for removal of thimerosal, a mercury-containing preservative, from vaccines. This action was prompted in part by a risk assessment from the Food and Drug Administration that is presented here. METHODS: The risk assessment consisted of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a metabolite of thimerosal) and methylmercury (a similar organic mercury compound) and to determine the doses at which toxicity occurs. Maximal potential exposure to mercury from vaccines was calculated for children at 6 months old and 2 years, under the US childhood immunization schedule, and compared with the limits for mercury exposure developed by the Environmental Protection Agency (EPA), the Agency for Toxic Substance and Disease Registry, the Food and Drug Administration, and the World Health Organization. RESULTS: Delayed-type hypersensitivity reactions from thimerosal exposure are well-recognized. Identified acute toxicity from inadvertent high-dose exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities. Depending on the immunization schedule, vaccine formulation, and infant weight, cumulative exposure of infants to mercury from thimerosal during the first 6 months of life may exceed EPA guidelines. CONCLUSION: Our review revealed no evidence of harm caused by doses of thimerosal in vaccines, except for local hypersensitivity reactions. However, some infants may be exposed to cumulative levels of mercury during the first 6 months of life that exceed EPA recommendations. Exposure of infants to mercury in vaccines can be reduced or eliminated by using products formulated without thimerosal as a preservative.

Animals↗

Thiomersal in vaccines: is removal warranted?

The mercury-based vaccine preservative thiomersal has come under scrutiny in recent months because of its presence in certain vaccines that provide the foundation of childhood immunisation schedules. Over the past decade new vaccines have been added to the recommended childhood schedule, and the relatively smaller bodyweight of infants has led to concern that the cumulative exposure of mercury from infant vaccines may exceed certain guidelines for the human consumption of mercury. In the US, government agencies and professional societies have recently recommended that thiomersal be removed altogether from vaccines. Some involved in developing vaccine policy feel that the evidence to support these safety concerns has not risen to the level required for such a response. This apparent divergence of opinion has left healthcare professionals and the public with uncertainty about the potential health effects from low level exposure to thiomersal as well as the necessity of removing thiomersal from vaccines. At present, scientific investigation has not found conclusive evidence of harm from thiomersal in vaccines. As a precautionary measure, efforts are under way to remove or replace thiomersal from vaccines and providers should anticipate the availability of more vaccine products that are thiomersal-free over the coming years.

Child↗

Singularity theory study of overdetermination in models for L-H transitions

Two dynamical models that have been proposed to describe transitions between low- and high-confinement states in confined plasmas are analyzed using singularity theory and stability theory. It is shown that the stationary-state bifurcation sets have qualitative properties identical to standard normal forms for the pitchfork and transcritical bifurcations. The analysis yields the codimension of the highest-order singularities, from which we find that the unperturbed systems are overdetermined bifurcation problems and derive appropriate universal unfoldings. Questions of mutual equivalence and the character of the state transitions are addressed.

Journal Article↗

Glutathione homeostasis and leukotriene-induced permeability in human blood-brain barrier endothelial cells subjected to in vitro ischemia.

Ischemic alterations in the glutathione (GSH) redox system of the blood-brain barrier (BBB) may facilitate oxidative injury and formation of vasogenic brain edema. In this study, both the intra- and extracellular GSH contents of human cerebromicrovascular endothelial cells (HCEC) were reduced by 35% after exposing the cells to 4 h in vitro ischemia and 24 h-recovery. The intracellular/extracellular GSH ratio was not affected, indicating a constant rate of GSH efflux. The activities of the peroxide detoxifying enzymes, glutathione peroxidase and glutathione S-transferase, increased by 35%-50%, whereas the GSH regenerating enzyme, glutathione reductase, remained unchanged in ischemic HCEC. gamma-glutamyl transpeptidase (GGTP), a GSH catabolizing enzyme enriched in brain capillaries, was reduced by 30-50% in ischemic HCEC. The effect of in vitro ischemia on HCEC permeability was assessed by measuring sodium fluorescein clearance across a compartmentalized in vitro BBB model. Sodium fluorescein clearance across HCEC monolayers exposed to leukotriene C4 in the presence of the GGTP inhibitor, acivicin (1 microM), or after in vitro ischemia was increased by 60% and 30%, respectively, suggesting that oxidative stress and loss of GGTP may 'unmask' BBB permeabilizing actions of leukotrienes. These results indicate that oxidative stress and loss of GGTP activity in HCEC contribute to ischemic BBB disruption and vasogenic brain edema.

Blood-Brain Barrier↗

A trial to determine the risk of decompression sickness after a 40 feet of sea water for 200 minute no-stop air dive.

BACKGROUND: The USN93 probabilistic model of decompression sickness (DCS) predicts a DCS risk of 3.9% after a 40 ft of seawater (fsw) for 200 min no-stop air dive, although little data is available to evaluate the accuracy of this prediction. Based on an analysis of Navy Safety Center data from diving on U.S. Navy standard air decompression tables, the observed incidence of DCS for this type of dive is 0.11%. Knowing the true incidence of the dive is important for deciding whether or not to adopt proposed probability based decompression procedures for U.S. Navy diving. HYPOTHESIS: The risk of DCS after a 40 fsw for 200 min no-stop air dive is 3.9%. METHODS: We conducted a closed sequential trial to determine the DCS incidence on this dive. RESULTS: Of 30 military divers who completed 91 dives, there were 2 cases of DCS (2.2%, 95% CI: 0.27 7.7%). The study was terminated early after the second DCS case because of the presence of neurological symptoms and signs. CONCLUSIONS: This study demonstrates that the incidence of DCS in a laboratory setting is higher than observed in fleet diving. Use of the 40 fsw for 200 min schedule in a decompression computer is likely to result in DCS incidence 2.5- to 70-fold greater than that observed in U.S. Navy diving using table-based procedures.

Adult↗

Escape from a disabled submarine: decompression sickness risk estimation.

Individual crewmember escape from a disabled U.S. Navy nuclear submarine has never been necessary, but remains an important contingency. Decompression sickness (DCS) is one of the foreseeable risks and a robust mathematical model of DCS incidence has been used to estimate the magnitude of this risk under a variety of escape scenarios. The model was calibrated with over 3000 well-controlled human pressure exposures, less than 2% of which simulated pressure profiles of submarine escape. For disabled submarine depths < 300 ft of sea water (fsw) and internal submarine pressures of <11 fsw (arguably the most likely conditions), the DCS risks are comparable to those routinely undertaken by U.S. Navy divers--less than 5%. For progressively deeper depths and especially for higher submarine internal pressures, the risk of DCS becomes much greater, including unknown chances of permanent injury and death. Variations from the baseline escape procedure are explored, including equipment differences, delays in exiting the submarine and changes in the oxygen content of the breathing mix.

Accidents↗