Improving acute care for older people at scale - the Acute Frailty Network.

Older people form a growing proportion and volume of those accessing urgent care. Non-specific presentations, multiple comorbidities and functional decline make assessment and management of this cohort challenging. Comprehensive Geriatric Assessment offers an evidence based framework to assess and mange older people, especially those with frailty. In this article we describe the CGA approach, underpinned by specific examples illustrating some of the key competencies required, and describe the role of the Acute Frailty Network (AFN). The AFN is a national improvement collaborative designed to support hospitals in delivering evidence based care for older people with frailty and urgent care needs. We describe the principles underlying the approach of the AFN, derived from working with over 20 hospitals, and some of the early successes.

Understanding mosquito host-choice behaviour: a new and low-cost method of identifying the sex of human hosts from mosquito blood meals.

BACKGROUND: Mosquito-borne diseases are a global health problem, causing hundreds of thousands of deaths per year. Pathogens are transmitted by mosquitoes feeding on the blood of an infected host and then feeding on a new host. Monitoring mosquito host-choice behaviour can help in many aspects of vector-borne disease control. Currently, it is possible to determine the host species and an individual human host from the blood meal of a mosquito by using genotyping to match the blood profile of local inhabitants. Epidemiological models generally assume that mosquito biting behaviour is random; however, numerous studies have shown that certain characteristics, e.g. genetic makeup and skin microbiota, make some individuals more attractive to mosquitoes than others. Analysing blood meals and illuminating host-choice behaviour will help re-evaluate and optimise disease transmission models. METHODS: We describe a new blood meal assay that identifies the sex of the person that a mosquito has bitten. The amelogenin locus (AMEL), a sex marker located on both X and Y chromosomes, was amplified by polymerase chain reaction in DNA extracted from blood-fed Aedes aegypti and Anopheles coluzzii. RESULTS: AMEL could be successfully amplified up to 24 h after a blood meal in 100% of An. coluzzii and 96.6% of Ae. aegypti, revealing the sex of humans that were fed on by individual mosquitoes. CONCLUSIONS: The method described here, developed using mosquitoes fed on volunteers, can be applied to field-caught mosquitoes to determine the host species and the biological sex of human hosts on which they have blood fed. Two important vector species were tested successfully in our laboratory experiments, demonstrating the potential of this technique to improve epidemiological models of vector-borne diseases. This viable and low-cost approach has the capacity to improve our understanding of vector-borne disease transmission, specifically gender differences in exposure and attractiveness to mosquitoes. The data gathered from field studies using our method can be used to shape new transmission models and aid in the implementation of more effective and targeted vector control strategies by enabling a better understanding of the drivers of vector-host interactions.

The neuronal transfer function: contributions from voltage- and time-dependent mechanisms.

The discovery that an array of voltage- and time-dependent channels is present in both the dendrites and soma of neurons has led to a variety of models for single-neuron computation. Most of these models, however, are based on experimental techniques that use simplified inputs of either single synaptic events or brief current injections. In this study, we used a more complex time-varying input to mimic the continuous barrage of synaptic input that neurons are likely to receive in vivo. Using dual whole-cell recordings of CA1 pyramidal neurons, we injected long-duration white-noise current into the dendrites. The amplitude variance of this stimulus was adjusted to produce either low subthreshold or high suprathreshold fluctuations of the somatic membrane potential. Somatic action potentials were produced in the high variance input condition. Applying a rigorous system-identification approach, we discovered that the neuronal input/output function was extremely well described by a model containing a linear bandpass filter followed by a nonlinear static-gain. Using computer models, we found that a range of voltage-dependent channel properties can readily account for the experimentally observed filtering in the neuronal input/output function. In addition, the bandpass signal processing of the neuronal input/output function was determined by the time-dependence of the channels. A simple active channel, however, could not account for the experimentally observed change in gain. These results suggest that nonlinear voltage- and time-dependent channels contribute to the linear filtering of the neuronal input/output function and that channel kinetics shape temporal signal processing in dendrites.

A genetic basis for anomalous band patterns encountered during DNA STR profiling.

Since 1995 the Forensic Science Service (FSS) has carried out DNA profiling of reference samples for the UK National DNA Database and in forensic casework using two multiplex STR profiling systems. During this period, profiles with anomalous banding patterns, although comparatively rare, have been encountered regularly. The FSS has collected instances of triallelic patterns and aberrant diallelic patterns. A systematic examination of these patterns has provided insight into their underlying genetic cause. The triallelic patterns could be classified into two types based on the relative intensities of their component alleles. In the Type 1 pattern the alleles were of uneven intensity, whereas in the Type 2 pattern, all three alleles were of even intensity. Evidence is presented that the more frequent Type 1 pattern is the result of somatic mutation at a heterozygous locus, and the Type 2 pattern is the result of a localized chromosomal rearrangement at a heterozygous locus. Directly from the Type 1 pattern, it was possible to deduce the size difference between the progenitor and mutated allele. All mutational changes were found to be multiples of four nucleotides, suggesting the loss or addition of one or more tetrameric repeat units. Aberrant diallelic patterns were identified by analysts due to an unexpectedly large difference in intensity between alleles at a heterozygous locus. While some of these diallelic patterns are likely caused by the same genetic phenomena described above occurring at a homozygous locus, others are demonstrated to be caused by a mutation in the primer binding sequence, leading to a reduction in amplification efficiency of one allele. It is concluded that based on a visual inspection of a profile, it is possible to infer a likely genetic basis directly from the triallelic pattern. By contrast, the aberrant diallelic patterns can be due to any one of a number of possible genetic effects.

Dendrite-to-soma input/output function of continuous time-varying signals in hippocampal CA1 pyramidal neurons.

We examined how hippocamal CA1 neurons process complex time-varying inputs that dendrites are likely to receive in vivo. We propose a functional model of the dendrite-to-soma input/output relationship that combines temporal integration and static-gain control mechanisms. Using simultaneous dual whole cell recordings, we injected 50 s of subthreshold and suprathreshold zero-mean white-noise current into the primary dendritic trunk along the proximal 2/3 of stratum radiatum and measured the membrane potential at the soma. Applying a nonlinear system-identification analysis, we found that a cascade of a linear filter followed by an adapting static-gain term fully accounted for the nonspiking input/output relationship between the dendrite and soma. The estimated filters contained a prominent band-pass region in the 1- to 10-Hz frequency range that remained constant as a function of stimulus variance. The gain of the dendrite-to-soma input/output relationship, in contrast, varied as a function of stimulus variance. When the contribution of the voltage-dependent current I(h) was eliminated, the estimated filters lost their band-pass properties and the gain regulation was substantially altered. Our findings suggest that the dendrite-to-soma input/output relationship for proximal apical inputs to CA1 pyramidal neurons is well described as a band-pass filter in the theta frequency range followed by a gain-control nonlinearity that dynamically adapts to the statistics of the input signal.