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Biomedical subjects

J M Heffernan

Publications and source records attributed to J M Heffernan.

5 recordsLinked to original sources

Improving estimates of the basic reproductive ratio: using both the mean and the dispersal of transition times.

In both within-host and epidemiological models of pathogen dynamics, the basic reproductive ratio, R(0), is a powerful tool for gauging the risk associated with an emerging pathogen, or for estimating the magnitude of required control measures. Techniques for estimating R(0), either from incidence data or in-host clinical measures, often rely on estimates of mean transition times, that is, the mean time before recovery, death or quarantine occurs. In many cases, however, either data or intuition may provide additional information about the dispersal of these transition times about the mean, even if the precise form of the underlying probability distribution remains unknown. For example, we may know that recovery typically occurs within a few days of the mean recovery time. In this paper we elucidate common situations in which R(0) is sensitive to the dispersal of transition times about their respective means. We then provide simple correction factors that may be applied to improve estimates of R(0) when not only the mean but also the standard deviation of transition times out of the infectious state can be estimated.

Disease Outbreaks↗

Perspectives on the basic reproductive ratio.

The basic reproductive ratio, R0, is defined as the expected number of secondary infections arising from a single individual during his or her entire infectious period, in a population of susceptibles. This concept is fundamental to the study of epidemiology and within-host pathogen dynamics. Most importantly, R0 often serves as a threshold parameter that predicts whether an infection will spread. Related parameters which share this threshold behaviour, however, may or may not give the true value of R0. In this paper we give a brief overview of common methods of formulating R0 and surrogate threshold parameters from deterministic, non-structured models. We also review common means of estimating R0 from epidemiological data. Finally, we survey the recent use of R0 in assessing emerging diseases, such as severe acute respiratory syndrome and avian influenza, a number of recent livestock diseases, and vector-borne diseases malaria, dengue and West Nile virus.

Animals↗

Temporal cortex synaptophysin mRNA is reduced in Alzheimer's disease and is negatively correlated with the severity of dementia.

We measured synaptophysin mRNA in neocortical tissue from 7 prospectively assessed, pathologically verified normal individuals, 17 subjects with Alzheimer's disease (AD), and 13 subjects with a non-AD dementia. In temporal cortex (Brodmann area 21), synaptophysin mRNA was decreased in AD and non-AD dementia groups compared to controls. The loss was also present relative to polyadenylated mRNA content. Synaptophysin mRNA signal correlated negatively with the degree of dementia and negatively with the pathological severity of AD. In occipital cortex (Brodmann area 17) there were no differences between groups nor clinicopathological correlations. These data extend the evidence for a regional synaptic pathology in AD which affects synaptic protein gene expression by temporal cortex neurons.

Aged↗

Amyloid precursor protein mRNAs in Alzheimer's disease.

Hybridization studies of mRNA link genetic with neurochemical and neuropathological approaches to Alzheimer's disease (AD). Here we review the distribution and abundance of amyloid precursor protein mRNAs in normal and AD-afflicted brains. The expression of apolipoprotein E and presenilin mRNAs are also discussed.

Alzheimer Disease↗

Effect of serotonin treatment on intestinal transport in the rabbit.

The hormone serotonin (5-hydroxytryptamine) has been implicated as the cause of the diarrhea seen in many patients with the carcinoid syndrome. To determine whether serotonin is an intestinal secretagogue, the effect of serotonin on intestinal water and electrolyte transport was evaluated in the rabbit. Two weeks of daily subcutaneous injection of serotonin suspended in oil resulted in a blood serotonin level elevated to twice that of controls. Intestinal transport was studied in vivo by a perfusion technique. Serotonin treatment resulted in ileal secretion and decreased mid-jejunal absorption of water and electrolytes but did not effect water absorption in the proximal jejunum or colon. Intestinal absorption of D-glucose and the amino acid L-tryptophan and glucose-dependent water and electrolyte absorption were normal in serotonin-treated animals. Serotonin-induced ileal secretion was reversed by methysergide, a peripheral antagonist of serotonin action. No alterations in intestinal histology or permeability occurred in serotonin-treated animals. Serotonin-induced intestinal secretion was not associated with alterations in the activities of intestinal mucosal adenylate cyclase, cyclic nucleotide phosphodiesterase, or Na-K-ATPase.

Animals↗