Age and Ageing to introduce a new category of paper: healthcare improvement science.

Age and Ageing is now inviting papers on healthcare improvement for older people. In this article we outline the nature and scope of healthcare improvement and reference improvement models and the tools and methods of improvement science. We emphasise the issues of sustainability, including scale and spread; evaluation - including associated ethical consideration and the involvement of patients and the public in healthcare improvement and associated research. Throughout we refer to resources the authors have found useful in their own work, and provide a bibliography of sources and web-links which will provide essential guidance and support for potential contributors to this new category of submission to Age and Ageing.

Quantum Estimation of Parameters of Classical Spacetimes.

We describe a quantum limit to measurement of classical spacetimes. Specifically, we formulate a quantum Cramér-Rao lower bound for estimating the single parameter in any one-parameter family of spacetime metrics. We employ the locally covariant formulation of quantum field theory in curved spacetime, which allows for a manifestly background-independent derivation. The result is an uncertainty relation that applies to all globally hyperbolic spacetimes. Among other examples, we apply our method to detection of gravitational waves with the electromagnetic field as a probe, as in laser-interferometric gravitational-wave detectors. Other applications are discussed, from terrestrial gravimetry to cosmology.

Entangling moving cavities in noninertial frames.

An open question in the field of relativistic quantum information is how parties in arbitrary motion may distribute and store quantum entanglement. We propose a scheme for storing quantum information in the field modes of cavities moving in flat space-time and analyze it in a quantum field theoretical framework. In contrast with previous work that found entanglement degradation between observers moving with uniform acceleration, we find the quantum information in such systems is protected. We further discuss a method for establishing the entanglement in the first place and show that in principle it is always possible to produce maximally entangled states between the cavities.

Optical performance of frequency-selective bolometers.

Frequency-selective bolometers (FSBs) are a new type of detector for millimeter and submillimeter wavelengths that are transparent to all but a narrow range of frequencies as set by characteristics of the absorber itself. Therefore stacks of FSBs tuned to different frequencies provide a low-loss compact method for utilizing a large fraction of the light collected by a telescope. Tests of prototype FSBs indicate that the absorption spectra are well predicted by models, that peak absolute absorption efficiencies of the order of 50% are attainable, and that their out-of-band transmission is high.

Ethical problems in clinical practice.

Ethics is about judgment, which is rarely black and white. This paper highlights some of the ethical dilemmas that face practising clinicians in their everyday life and restates how useful the General Medical Council guidance is to make appropriate decisions. The authors have faced all eight of the clinical scenarios in this paper in their routine clinical practice.

Ocean PHILLS hyperspectral imager: design, characterization, and calibration.

The Ocean Portable Hyperspectral Imager for Low-Light Spectroscopy (Ocean PHILLS) is a hyperspectral imager specifically designed for imaging the coastal ocean. It uses a thinned, backsideilluminated CCD for high sensitivity and an all-reflective spectrograph with a convex grating in an Offner configuration to produce a nearly distortionfree image. The sensor, which was constructed entirely from commercially available components, has been successfully deployed during several oceanographic experiments in 1999-2001. Here we describe the instrument design and present the results of laboratory characterization and calibration. We also present examples of remote-sensing reflectance data obtained from the LEO-15 site in New Jersey that agrees well with ground-truth measurements.

Derivative analysis of absorption features in hyperspectral remote sensing data of carbonate sediments.

This study uses derivative spectroscopy to assess qualitative and quantitative information regarding seafloor types that can be extracted from hyperspectral remote sensing reflectance signals. Carbonate sediments with variable concentrations of microbial pigments were used as a model system. Reflectance signals measured directly over sediment bottoms were compared with remotely sensed data from the same sites collected using an airborne sensor. Absorption features associated with accessory pigments in the sediments were lost to the water column. However major sediment pigments, chlorophyll a and fucoxanthin, were identified in the remote sensing spectra and showed quantitative correlation with sediment pigment concentrations. Derivative spectra were also used to create a simple bathymetric algorithm.

Self-shading correction for upwelling sea-surface radiance measurements made with buoyed instruments.

Upwelling radiance measurements made with instruments designed to float at the sea surface are shaded both by the instrument housing and by the buoy that holds the instrument. The amount of shading is wavelength dependent and is affected by the local marine and atmospheric conditions. Radiance measurements made with such instruments should be corrected for this self-shading error before being applied to remote sensing calibrations or remote sensing algorithm validation. Here we use Monte Carlo simulations to compute the self-shading error of a commercially available buoyed radiometer so that measurements made with this instrument can be improved. This approach can be easily adapted to the dimensions of other instruments.

Analysis of a point-source integrating-cavity absorption meter.

We evaluate the theoretical performance of a point-source integrating-cavity absorption meter (PSICAM) with Monte Carlo simulations and a sensitivity analysis. We quantify the scattering errors, verifying that they are negligible for most ocean optics applications. Although the PSICAM detector response is highly sensitive to the value of the wall reflectivity, the absorption of an unknown fluid can be accurately determined with a PSICAM if appropriate reference solution(s) are chosen. We also quantify the error that results if the source is not perfectly isotropic, finding that moderate amounts of source anisotropy can be tolerated provided that the detector is properly located with respect to the source.

Moderate sodium restriction does not alter lower body negative pressure tolerance.

HYPOTHESIS: Space travel with exposure to microgravity leads to a significant reduction in orthostatic tolerance on return to Earth, for which countermeasures are only partially successful. The purpose of this study was to examine the effect of moderate dietary sodium restriction on tolerance to LBNP. METHODS: Eight healthy men, age 25.1+/-1.3 yr, volunteered for the study. Subjects were exposed to presyncopal LBNP after consuming their "typical" diet (C) for 5 d and after consuming a sodium restricted (SR) diet for 5 d. Diet sequence was randomized and adherence was verified by 24-h urine collection on the 4th and 5th days of each diet. RESULTS: All subjects reached presyncope during the LBNP, regardless of diet. Urinary sodium excretion was 3390+/-950 mg on the C diet and 1174+/-560 mg on the SR diet. Urinary potassium was not different between the diets. Cumulative stress index scores were 655+/-460 (mm Hg x min) on the C diet and 639+/-388 (mm Hg x min) during SR. Cardiac volumes, BP and total peripheral resistance were not different at any stage of the LBNP between the diets, nor were catecholamines. Plasma renin activity, determined by radioimmunoassay, was significantly higher during SR at rest, and during all stages of LBNP in comparison with the control diet. CONCLUSION: Moderate dietary sodium restriction is not detrimental to orthostatic tolerance.

The heart is not necessarily empty at syncope.

BACKGROUND: Although extensively investigated, the mechanism(s) of post-spaceflight orthostatic intolerance has not been elucidated. Several researchers have proposed that the "trigger" for syncope is an empty ventricle, initiated when a hypercontractile state, possibly due to a sudden surge in epinephrine, causes the walls of the left ventricle to touch leading to a profound sympatho-inhibition and intense vagal stimulation. HYPOTHESIS: A markedly reduced left ventricular end systolic volume (LVESV) achieved during progressive, presyncopal-limited lower body negative pressure (LBNP) is the trigger for syncope. METHODS: Eight healthy men, age 25.1+/-1.3 yr, volunteered for the study. Changes in left ventricular end-diastolic volume and LVESV were measured, using two-dimensional echocardiography, at each stage of LBNP from rest up to presyncope (PS). Plasma venous catecholamine concentrations were measured at the end of each stage by high performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: All subjects reached PS. Three men became bradycardic at presyncope while five remained tachycardic. LVESV decreased by 28% at PS with no evidence of ventricular cavity obliteration. Norepinephrine increased by 44% from rest to PS, but no epinephrine surge was detected (35% increase from rest to PS). CONCLUSION: These data indicate that it is possible to initiate syncope with only a 28% decrease in LVESV, and that sympatho-inhibition and bradycardia are not required elements for syncope to occur.

Validation of impedance cardiography during lower body negative pressure.

BACKGROUND: Both echocardiographic and impedance cardiographic techniques have been used individually for the determination of stroke volume (SV) during lower body negative pressure (LBNP). Impedance cardiography has not been validated during LBNP. HYPOTHESIS: The purpose of this study was to determine both the absolute values for SV and the change in SV for each stage of LBNP using both impedance and echocardiographic techniques during staged LBNP to presyncope. The hypothesis was that there would be no difference between the two techniques for either the absolute values of SV or for the change in SV with each stage of LBNP. METHODS: There were 16 men who volunteered to undergo LBNP. LBNP was lowered in 10 mmHg stages for 5 min per stage until presyncope was reached. Left ventricular SV was determined by two-dimensional echocardiography and impedance cardiography. Both the absolute values for SV and the change in SV from baseline at each stage of LBNP were compared for the two methods. RESULTS: There were no significant differences between the two techniques for the measurement of either the absolute SV or the change in SV with LBNP. The two methods correlated highly with r = 0.89 for the absolute SV values and r = 0.93 for the change in SV. Graphical analysis with the Bland-Altman analysis showed little bias in the impedance measurement for SV (-0.031 ml) and the change in SV (-2.7 ml). CONCLUSIONS: Impedance cardiography was a reliable measure of SV, as well as the change in SV, during LBNP stress to presyncope.

Immediate angioplasty for acute myocardial infarction: a community hospital's experience.

This study describes prospective outcome data from 100 consecutive patients presenting with acute myocardial infarction and treated with immediate angioplasty in a community hospital setting. Successful angioplasty was achieved in 86% of patients with a mean reperfusion time of 77.5 minutes. Only 4 patients did not survive initial hospitalization; three of these initially presented with cardiogenic shock. The survival rate in noncardiogenic shock patients was 98.9%. Four patients underwent repeat angioplasty of the infarct-related artery and 6 patients were referred for coronary artery bypass surgery during initial hospitalization. During the 6 month follow-up, nine patients required repeat hospitalization. Seven of these patients presented with recurrent ischemia; four underwent repeat angioplasty and 3 coronary artery bypass surgery. There were no subsequent deaths or reinfarctions during the 6 month follow-up. The angioplasty success rate and clinical outcomes in this study compare favorably to previous trials performed in select interventional centers and suggest that immediate angioplasty can be the preferred reperfusion therapy in a community hospital setting.

Automated short tandem repeat (STR) analysis in forensic casework--a strategy for the future.

Short tandem repeat (STR) loci are routinely analysed for forensic purposes in the UK. Because small regions of DNa are amplified, successful results are more likely to be obtained from highly degraded material where the DNA fragment length may be < 500 bp. The method is superceeding conventional analysis with single locus probes (SLPs). Dimeric STR loci display stutter artefacts, hence STRs used in casework are restricted to tri or tetrameric loci. Some STRs are complex repeats and have more alleles than simple repeats - for example the locus D21S11 has 21 alleles which differ in size by 2 bp because of the presence/absence of a hexanucleotide within the block of tetrameric repeats. These loci are of great potential interest because they combine increased discriminating power with reduced potential to stutter. Multiplexing 4 different loci with different dye labelled primers (i.e. carrying out polymerase chain reaction of 4 loci simultaneously) using the ABD 373A automated sequencer enables a large numbers of samples to be processed. In addition data aquisition and manipulation is automated so that minimum postelectrophoresis operator input is required. It is our aim to develop a system equivalent in power to that of 4 single locus probes. To achieve this we have developed an octoplex system consisting of 7 loci and a sex test (amelogenin locus) which has a probability of chance of association of 10(-9); the power of this system is equivalent to that achieved by 4 conventional SLPs.

Short tandem repeat typing of bodies from a mass disaster: high success rate and characteristic amplification patterns in highly degraded samples.

We have used a PCR-based DNA-typing method, involving the coamplification of four tetrameric short tandem repeat loci, in the analysis of a large number of severely degraded tissue samples taken from the scene of a mass disaster in which bodies were exposed to extreme thermal, physical and chemical insult. Analysis of the amplified DNA in a number of the samples revealed uniquely sized artifact PCR products resulting from the amplification of degraded genomic DNA as well as characteristic patterns in the amounts of PCR products generated from differently sized loci. This system has proved to be very reliable and robust, and we were successful in typing all of the four loci in 66% of the samples tested and at least one locus in 83% of the cases. A PCR-based sex test also proved to be very effective when applied to the degraded samples.

A highly discriminating octoplex short tandem repeat polymerase chain reaction system suitable for human individual identification.

Through the use of fluorescence-based polymerase chain reaction systems, a highly discriminating multiplex with the potential for individual identification has been developed. The use of multiple dye technology enabling loci with overlapping size ranges to be co-amplified has enabled us to successfully amplify seven tetranucleotide short tandem repeat loci within a single reaction resulting in a discriminating power in the region of 1 x 10(9). Three out of the seven loci employed exhibit alleles differing in size by only 2 bp as opposed to the conventional 4 bp, which results in such loci being more powerful in terms of distinguishing between samples, particularly when co-amplified in this manner. The size ranges of the loci contained within the system are such that windows still exist for the inclusion of additional loci at a later stage, which could increase the discriminating power of the system still further. In addition, further weight and utility is lent to the system through the incorporation of a simple and reliable sex test involving the amplification of a segment of the X-Y homologous gene Amelogenin.

Variation in short tandem repeat sequences--a survey of twelve microsatellite loci for use as forensic identification markers.

Alleles at 12 Short Tandem Repeat loci have been sequenced to investigate candidate loci for a multiplex Short Tandem Repeat system for forensic identification, and for single-locus amplification of Short Tandem Repeat loci. Variation from the consensus sequence was found at 6 loci, while one locus, D21S11, was found to be complex in sequence. The presence of non-consensus alleles does not rule out loci for inclusion as forensic identification markers, but size differences between alleles of 1 base pair require very precise sizing. We suggest criteria for the suitability of Short Tandem Repeat loci as forensic identification markers, and propose a universal allele nomenclature for simple and compound Short Tandem Repeats. The effect of the repeat unit sequence of the evolution of Short Tandem Repeats is discussed.