Leukocyte telomere length in the Thoroughbred racehorse.

Thoroughbred racehorses possess superior cardiorespiratory fitness levels and are at the pinnacle of athletic performance compared to other breeds of horses. Although equine athletes have undergone years of artificial selection for racing performance, musculoskeletal injuries and illnesses are common and concerns relating to animal welfare have been proposed. Leukocyte telomere length is indicative of biological age, and accelerated telomere shortening occurs with excess physical and psychological stress. This study was designed to explore the association between leukocyte telomere length, biological factors (age, sex and coat colour), training status, winnings and race history parameters. Blood was collected from 146 Thoroughbred racehorses from around Geelong, Victoria, Australia. DNA was extracted from leukocytes; telomere length was measured using qPCR and analysed in context with traits obtained from the Racing Australia website. Age was inversely correlated with telomere length (r = -0.194, P = 0.019). The oldest horses (≥11 years) in the highest age quartile possessed shorter telomeres compared to younger horses in the first, second and third quartiles (≤2, 3-5 and 6-10 years respectively; P < 0.05). No statistically significant associations were observed between telomere length and biological factors, training status, winnings or race history parameters in age-adjusted analyses. The study findings suggest that Thoroughbred horses may undergo age-related telomere shortening similar to other mixed breeds and humans. Despite concerns from some quarters regarding the welfare of racehorses, there was a lack of accelerated biological ageing observed in the present study, as indicated by leukocyte telomere length.

Radioiodine Biogeochemistry and Prevalence in Groundwater.

129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these knowledge gaps will not alter the observation that 129I is primarily mobile, but it will likely permit demonstration that the entire 129I pool in the source term is not moving at the same rate and some may be tightly bound to the sediment, thereby smearing the modeled 129I peak and reducing maximum calculated risk.

Dr Marjory Warren CBE MRCS LRCP (1897-1960): the mother of British geriatric medicine.

Dr Marjory Warren was a remarkable, formidable physician who reversed the neglect of chronic sick patients and brought their treatment into the modern era. She advocated the creation of the specialty of geriatric medicine with units based in district general hospitals, and that medical students and nurses should be taught about the diseases of old age. She treated the whole patient, applied advances in medicine and therapeutics, devised new techniques and equipment to assist disabled elderly stroke and amputee patients, and made great improvements in the ward environment. She emphasized the importance of the patient's social background, and electrified both staff and patients with her drive and enthusiasm. Many patients were treated successfully and discharged. Bed requirements were reduced and vacated wards allocated for other uses. She wrote extensively and lectured across the world to national and international approbation.

Professor Arthur Norman Exton-Smith CBE MA MD FRCP (1920-90): distinguished geriatrician and gerontologist.

Professor Norman Exton-Smith was a highly respected, distinguished postwar consultant geriatrician with a worldwide reputation. He devoted his life to improving the medical care of elderly people and researching age-related decline in physical function, particularly thermoregulation and postural balance. He established thriving clinical and research departments at St Pancras Hospital, London. Many of his junior medical staff became well-known geriatricians. He published and lectured extensively, organized many meetings and conferences, and was advisor to the Department of Health and Social Security for many years. He was a valued authority on geriatric medicine within the Royal College of Physicians of London and a major influence in the British Geriatrics Society (BGS) of which he was Secretary and later the President.

The linearity of emergent spectro-temporal receptive fields in a model of auditory cortex.

The responses of cortical neurons are often characterized by measuring their spectro-temporal receptive fields (STRFs). The STRF of a cell can be thought of as a representation of its stimulus 'preference' but it is also a filter or 'kernel' that represents the best linear prediction of the response of that cell to any stimulus. A range of in vivo STRFs with varying properties have been reported in various species, although none in humans. Using a computational model it has been shown that responses of ensembles of artificial STRFs, derived from limited sets of formative stimuli, preserve information about utterance class and prosody as well as the identity and sex of the speaker in a model speech classification system. In this work we help to put this idea on a biologically plausible footing by developing a simple model thalamo-cortical system built of conductance based neurons and synapses some of which exhibit spike-time-dependent plasticity. We show that the neurons in such a model when exposed to formative stimuli develop STRFs with varying temporal properties exhibiting a range of heterotopic integration. These model neurons also, in common with neurons measured in vivo, exhibit a wide range of non-linearities; this deviation from linearity can be exposed by characterizing the difference between the measured response of each neuron to a stimulus, and the response predicted by the STRF estimated for that neuron. The proposed model, with its simple architecture, learning rule, and modest number of neurons (<1000), is suitable for implementation in neuromorphic analogue VLSI hardware and hence could form the basis of a developmental, real time, neuromorphic sound classification system.

Lord Amulree: an appreciation.

Lord Amulree was unique amongst UK geriatricians in having a 'wide angled' view of the care of elderly people. This resulted from his work at the Ministry of Health, his clinical commitments and his position in the House of Lords, which enabled him to bring the problems of old age, elderly people and infirmity before a much wider audience. It can be argued that his joint Parliamentary Presentation in 1946 stimulated a surge in publications relating to the care of older people. He will be remembered for his maxim 'Adding Life to Years'

MAC5: Bayesian inference of phylogenetic trees from DNA sequences incorporating gaps.

SUMMARY: MAC5 implements MCMC sampling of the posterior distribution of tree topologies from DNA sequences containing gaps by using a five state model of evolution (the four nucleotides and the gap character).

Neonatal size of low socio-economic status Black and White term births in Albany County, NYS.

Birth weight has long been a focus of study by epidemiologists and human biologists, because it reflects the quality of the intrauterine environment and may be used as a predictor of future growth and development. Comparisons of Black and White neonates in the USA have consistently shown differences in birth weight. Confounding variables are a major problem in any such investigation, especially socio-economic status which is highly correlated with race in the USA. This study was distinctive in the sampling of one socio-economic stratum (low income), and the use of five anthropometric measures in addition to birth weight. The goals of this study were as follows: to determine if there were differences in body size and body composition at birth in Black and White neonates of low socio-economic status (SES), and to investigate what variables might account for any observed variability. The sample consisted of full term Black and White neonates of low SES (n = 323) born in Albany, NY (1986-1997). Birth weight, length, head and arm circumference, and subscapular and triceps skinfolds were compared. Race was determined through maternal self-identification. White neonates were significantly larger than Black neonates in birth weight, length and head circumference. Among female neonates none of the anthropometric dimensions differed between Blacks and Whites. Among male neonates, Whites were significantly larger than Blacks in birth weight, length, head and arm circumferences. Principal components analysis reduced the six anthropometric dimensions to two summary measures: body size and composition. When controlling for social and biological variables, race and sex were significant predictors of body composition, but not body size. Interpretation of results and possible causal relationships are discussed.

Oscillatory model of novelty detection.

A model of novelty detection is developed which is based on an oscillatory mechanism of memory formation and information processing. The frequency encoding of the input information and adaptation of natural frequencies of network oscillators to the frequency of the input signal are used as the mechanism of information storage. The resonance amplification of network activity is used as a recognition principle for familiar stimuli. Application of the model to novelty detection in the hippocampus is discussed.

Models of sequence evolution for DNA sequences containing gaps.

Most evolutionary tree estimation methods for DNA sequences ignore or inefficiently use the phylogenetic information contained within shared patterns of gaps. This is largely due to the computational difficulties in implementing models for insertions and deletions. A simple way to incorporate this information is to treat a gap as a fifth character (with the four nucleotides being the other four) and to incorporate it within a Markov model of nucleotide substitution. This idea has been dismissed in the past, since it treats a multiple-site insertion or deletion as a sequence of independent events rather than a single event. While this is true, we have found that under many circumstances it is better to incorporate gap information inadequately than to ignore it, at least for topology estimation. We propose an extension to a class of nucleotide substitution models to incorporate the gap character and show that, for data sets (both real and simulated) with short and medium gaps, these models do lead to effective use of the information contained within insertions and deletions. We also implement an ad hoc method in which the likelihood at columns containing multiple-site gaps is downweighted in order to avoid giving them undue influence. The precision of the estimated tree, assessed using Markov chain Monte Carlo techniques to find the posterior distribution over tree space, improves under these five-state models compared with standard methods which effectively ignore gaps.

Over-the-counter medicines and the elderly.

Sales of over-the-counter (OTC) medicines are rising, and will continue to rise as more products are reclassified from prescription-only status to OTC medicines (either pharmacy-only or general sales list). Patients and doctors often omit discussion of OTC medicines when giving or taking a medication history. This has serious potential for identifying adverse drug reactions and drug-drug interactions, which are more common in older people. Therefore, medication histories should include documentation of any OTC medicines taken.

The problems of using the transmission/disequilibrium test to infer tight linkage.

Family-based association methods such as the transmission/disequilibrium test (TDT) have become very popular during the past few years, often being preferred to case-control studies because family-based approaches avoid the difficulties of ascertainment of appropriate populations of cases and controls for case-control studies. Significant TDT results indicate both linkage and allelic association. However, significant TDT results are often interpreted as implying tight linkage of marker and disease locus, and we shall argue here that, in general, this interpretation is not justified.

Marker-assisted selection using ridge regression.

In cross between inbred lines, linear regression can be used to estimate the correlation of markers with a trait of interest; these marker effects then allow marker assisted selection (MAS) for quantitative traits. Usually a subset of markers to include in the model must be selected: no completely satisfactory method of doing this exists. We show that replacing this selection of markers by ridge regression can improve the mean response to selection and reduce the variability of selection response.

A model of theta rhythm production in the septal-hippocampal system and its modulation by ascending brain stem pathways.

Recent experimental observations have disclosed the existence of a septal-hippocampal feedback circuit, composed of medial septum diagonal band of Broca (ms-dbB) GABAergic projections to the inhibitory interneurons of the hippocampus, and hippocampal GABAergic projections to the ms-dbB, the major targets of which are the GABAergic septo-hippocampal projection cells. We propose that this feedback circuit provides the mechanism for the rhythmic suppression of interneuronal activity in the hippocampus, which is observed as low-level GABAergic-mediated theta activity. We also propose that this circuit may be the mechanism by which ascending brain stem pathways to the ms-dbB, in particular from the reticular formation, can influence hippocampal information processing in response to particular behavioral states, by exercising control over the level and frequency of theta activity in the hippocampus. In support of these proposals, we describe a minimal computational model of the feedback circuit which uses a set of four coupled differential equations describing the average dynamic activity of the populations of excitatory and inhibitory cells involved in the circuit. We demonstrate through simulations the inherently robust 4-6-Hz oscillatory dynamics of the circuit, and show that manipulation of internal connection strengths and external modulatory influences on this circuit changes the dynamics in a way which closely mimics corresponding manipulations in recent neurophysiological experiments investigating theta activity.

An oscillatory neural network model of sparse distributed memory and novelty detection.

A model of sparse distributed memory is developed that is based on phase relations between the incoming signals and an oscillatory mechanism for information processing. This includes phase-frequency encoding of input information, natural frequency adaptation among the network oscillators for storage of input signals, and a resonance amplification mechanism that responds to familiar stimuli. Simulations of this model show different types of dynamics in response to new and familiar stimuli. The application of the model to hippocampal working memory is discussed.

Computational models of predictive and memory-related functions of the hippocampus.

We discuss the role of the hippocampus in information processing in the brain and hypothesise that the hippocampus monitors the stability of sensory cues it receives from the external world, using the current context to predict the next sensory event in the episodic sequence by learning from experience, and memorising these sequences of sensory events. Two computational models are presented here. The predictive theory and model are closely related to experimental evidence and use dynamic synapses with an asymmetric learning rule to develop predictive neural activity of a leaky integrate-and-fire model of a pyramidal CA3 cell. The oscillatory model of the hippocampus for memorising sequences of sensory events is developed as a chain of interacting neural oscillators forced by oscillatory inputs from the entorhinal cortex and from the medial septum.

Long-term care. Strike up the bands.

Assessing elderly people for long-term care according to a banding system, with the assessors meeting weekly, can speed up placements. The system is believed to cut down on inappropriate placements. A rise in the number of elderly people in nursing home places funded by the local authority reflects increasing levels of dependence in the community.

Drug therapy and the older person: role of the pharmacist.

Older people in the UK receive a disproportionate amount of medication. They comprise 18% of the population but receive 45% of all prescription items. Not surprisingly they experience drug-related illnesses - in 1980, 1 in 10 admissions to acute geriatric units were wholly or partly due to adverse drug reactions. Drugs which should be used with particular care or even avoided in older people include benzodiazepines, warfarin, digoxin, aminoglycosides, tricylic antidepressants, antipsychotics and long-acting oral hypoglycaemic agents. Pharmacists can promote safer prescribing practices by advising both patients and doctors. The community pharmacist can assist in drug compliance by providing patients with additional information about individual drugs, identifying potential adverse drug reactions and interactions, supplying appropriate drug containers or compliance aids, and even arranging home visits for patients unable to visit the pharmacist. Some community pharmacists provide pharmaceutical advice and services to residential and nursing homes. Pharmacists' advice to doctors can include one to one discussions in either primary or secondary care, assisting in medication review, providing information to prescribing committees, compiling drug formularies, assisting in auditing of prescribing practices and organising disposal of unwanted medicines and poisons campaigns.