Exploring rehabilitation potential in older people living with frailty: a qualitative focus group study.

BACKGROUND: Rehabilitation interventions are frequently cited as key in supporting frail older people's recovery following periods of decompensation and acute ill-health. Clinicians are required to make decisions about a patient's potential to respond to rehabilitation. 'Rehabilitation potential' decisions can determine access to services. In acute settings clinicians have limited time to assess and work with patients, families and carers. The complexities of ageing, recovery, rehabilitation and frailty may not be fully appreciated. This study aimed to explore multiple perspectives of the concept of rehabilitation potential and how it is assessed in older people living with frailty in the acute healthcare setting. METHODS: Five focus groups with a purposive sample of 28 participants which included clinicians and members of the public were conducted. Analysis comprised a thematic approach using the Framework method. RESULTS: Rehabilitation potential was found to encapsulate a complex decision-making process where clinicians judged an individual's ability to benefit from and participate in targeted rehabilitation. They asked, "Will it work?", "Is it wanted?" and "Is it available?" In order to predict who would benefit from rehabilitation interventions, clinicians assessed a range of holistic clinical and non-clinical factors. An iterative approach to assessment delivered by a multi-disciplinary team, centred around patient and carer needs and wants was needed to accommodate complexity. Participants believed that everyone had some form of potential but this was dependent on availability of rehabilitation resources and conceptualisations of frailty and rehabilitation. Tensions between iterative approaches to rehabilitation potential assessment and the realities of rapid decision making in the acute hospital setting were found. CONCLUSION: Rehabilitation potential decisions involve a complex process of multidisciplinary decision-making and prognostication on the likely outcome and benefit from rehabilitation programmes. These findings lay the foundation for developing structured approaches to rehabilitation potential decision making tools and guidance.

EAC-1A: A novel large-volume lunar regolith simulant.

The European Astronaut Centre (EAC) is currently constructing the European Lunar Exploration Laboratory (LUNA), a large training and operations facility to be located adjacent to EAC at the DLR (German Aerospace Centre) campus in Cologne, Germany. With an estimated representative lunar testbed area of approximately 660 m2, a large volume of lunar regolith simulant material is needed for this purpose. In this study, a basanitic sandy silt from a quarry located in the Siebengebirge Volcanic Field is evaluated as a large-volume source of material. The focus of this project has been to conduct a physical and chemical characterisation of the fine-grained material to be used in LUNA; the European Astronaut Centre lunar regolith simulant 1 (EAC-1 A). The physical characterisation tests undertaken include sphericity, density measurements, cohesion and static angle of repose, with mineralogical investigations via petrographical analysis with optical microscope and SEM, XRF, XRD and DSC measurements. The results of the EAC-1A tests are compared to published data on existing widely used lunar regolith simulants, namely JSC-1A, JSC-2A, NU-LHT-3M, DNA and FJS-1.

Nondestructive X-ray diffraction measurement of warpage in silicon dies embedded in integrated circuit packages.

Transmission X-ray diffraction imaging in both monochromatic and white beam section mode has been used to measure quantitatively the displacement and warpage stress in encapsulated silicon devices. The displacement dependence with position on the die was found to agree well with that predicted from a simple model of warpage stress. For uQFN microcontrollers, glued only at the corners, the measured misorientation contours are consistent with those predicted using finite element analysis. The absolute displacement, measured along a line through the die centre, was comparable to that reported independently by high-resolution X-ray diffraction and optical interferometry of similar samples. It is demonstrated that the precision is greater than the spread of values found in randomly selected batches of commercial devices, making the techniques viable for industrial inspection purposes.

Controlling wettability of PECVD-deposited dual organosilicon/carboxylic acid films to influence DNA hybridisation assay efficiency.

Herein, plasma polymerisation of a dual-layer tetraethyl orthosilicate (TEOS) and acrylic acid (AA) film under a specific recipe is performed. Newly deposited films are found to retain a weakly-bound soft layer of partially polymerised acrylic acid (wbAA), which can be ultimately removed by washing. However, when on the surface, this soft layer is shown to be influential in manipulating the properties of a robust covalently-bound AA (cbAA) underlayer when treated appropriately. Specifically, treatment of the as-deposited dual-layer TEOS/AA films via timed incubation in a humidity-controlled environment results in changes in the water contact angle (WCA) of the cbAA, and ultimately the surface of the TEOS/AA, enabling tuning of the wettability of the acrylic acid layer. Through the use of a controlled incubation environment of the TEOS/AA, followed by washing, we have demonstrated that carboxylic-acid containing surfaces with a WCA between 85° and 10° can be routinely generated, using basic apparatus and simple methodology. Moreover, these surfaces not only retain their AA functionality, demonstrated by covalent-linking of amine-terminated single-stranded DNA, but also strongly inhibit non-specific binding of the DNA strands. The efficiency of these surfaces to be used in DNA direct-binding hybridisation assays has been demonstrated, with limits of detection of 1.11 and 1.66 nM being measured.

Cicada Wing Surface Topography: An Investigation into the Bactericidal Properties of Nanostructural Features.

Recently, the surface of the wings of the Psaltoda claripennis cicada species has been shown to possess bactericidal properties and it has been suggested that the nanostructure present on the wings was responsible for the bacterial death. We have studied the surface-based nanostructure and bactericidal activity of the wings of three different cicadas (Megapomponia intermedia, Ayuthia spectabile and Cryptotympana aguila) in order to correlate the relationship between the observed surface topographical features and their bactericidal properties. Atomic force microscopy and scanning electron microscopy performed in this study revealed that the tested wing species contained a highly uniform, nanopillar structure on the surface. The bactericidal properties of the cicada wings were investigated by assessing the viability of autofluorescent Pseudomonas fluorescens cells following static adhesion assays and targeted dead/live fluorescence staining through direct microscopic counting methods. These experiments revealed a 20-25% bacterial surface coverage on all tested wing species; however, significant bactericidal properties were observed in the M. intermedia and C. aguila species as revealed by the high dead:live cell ratio on their surfaces. The combined results suggest a strong correlation between the bactericidal properties of the wings and the scale of the nanotopography present on the different wing surfaces.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat.

Influence of substrate metal alloy type on the properties of hydroxyapatite coatings deposited using a novel ambient temperature deposition technique.

Hydroxyapatite (HA) coatings are applied widely to enhance the level of osteointegration onto orthopedic implants. Atmospheric plasma spray (APS) is typically used for the deposition of these coatings; however, HA crystalline changes regularly occur during this high-thermal process. This article reports on the evaluation of a novel low-temperature (<47°C) HA deposition technique, called CoBlast, for the application of crystalline HA coatings. To-date, reports on the CoBlast technique have been limited to titanium alloy substrates. This study addresses the suitability of the CoBlast technique for the deposition of HA coatings on a number of alternative metal alloys utilized in the fabrication of orthopedic devices. In addition to titanium grade 5, both cobalt chromium and stainless steel 316 were investigated. In this study, HA coatings were deposited using both the CoBlast and the plasma sprayed techniques, and the resultant HA coating and substrate properties were evaluated and compared. The CoBlast-deposited HA coatings were found to present similar surface morphologies, interfacial properties, and composition irrespective of the substrate alloy type. Coating thickness however displayed some variation with the substrate alloy, ranging from 2.0 to 3.0 µm. This perhaps is associated with the electronegativity of the metal alloys. The APS-treated samples exhibited evidence of both coating, and significantly, substrate phase alterations for two metal alloys; titanium grade 5 and cobalt chrome. Conversely, the CoBlast-processed samples exhibited no phase changes in the substrates after depositions. The APS alterations were attributed to the brief, but high-intensity temperatures experienced during processing.

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population.

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.

Application of a computational model of vagus nerve stimulation.

OBJECTIVES: The most widely used and studied neurostimulation procedure for medically refractory epilepsy is vagus nerve stimulation (VNS) Therapy. The goal of this study was to develop a computational model for improved understanding of the anatomy and neurophysiology of the vagus nerve as it pertains to the principles of electrical stimulation, aiming to provide clinicians with a systematic and rational understanding of VNS Therapy. MATERIALS AND METHODS: Computational modeling allows the study of electrical stimulation of peripheral nerves. We used finite element electric field models of the vagus nerve with VNS Therapy electrodes to calculate the voltage field for several output currents and studied the effects of two programmable parameters (output current and pulse width) on optimal fiber activation. RESULTS: The mathematical models correlated well with strength-duration curves constructed from actual patient data. In addition, digital constructs of chronic versus acute implant models demonstrated that at a given pulse width and current combination, presence of a 110-µm fibrotic tissue can decrease fiber activation by 50%. Based on our findings, a range of output current settings between 0.75 and 1.75 mA with pulse width settings of 250 or 500 µs may result in optimal stimulation. CONCLUSIONS: The modeling illustrates how to achieve full or nearly full activation of the myelinated fibers of the vagus nerve through output current and pulse width settings. This knowledge will enable clinicians to apply these principles for optimal vagus nerve activation and proceed to adjust duty cycle and frequency to achieve effectiveness.

Pseudo-aneurysm of the profunda femoris artery as a late complication of hip fracture in a patient with myelodysplasia.

We report a pseudo-aneurysm of the profunda femoris artery that resulted in intermittent bleeding and pain 6 weeks following dynamic hip screw fixation of an intertrochanteric hip fracture. Early diagnosis by angiogram could have minimised significant patient morbidity in this case.

Transverse beam spin asymmetries in forward-angle elastic electron-proton scattering.

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely polarized 3 GeV electrons from unpolarized protons at Q2=0.15, 0.25 (GeV/c)2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A(n) provides a direct probe of the imaginary component of the 2gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension.

The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains.

To understand the genetic basis of pathways involved in the control of breathing, a large scale, high-throughput study using chromosomal substitution strains of rats is underway. Eight new consomic rat stains (SS-2(BN), SS-4(BN), SS-6(BN), SS-7(BN), SS-8(BN), SS-11(BN), SS-12(BN), SS-14(BN), SS-Y(BN)), containing one homozygous BN/NHsdMcwi (BN) chromosome on a background of SS/JrHsdMcwi (SS), were created by PhysGen (http://pga.mcw.edu) Program for Genomic Applications. Male and female rats were studied using standard plethysmography under control conditions and during acute hypoxia (inspired oxygen fraction = 0.12) and hypercapnia (inspired CO(2) fraction = 0.07). The rats were also studied during treadmill exercise. Both male and female BN rats had a significantly lower ventilatory response during 7% CO(2) compared with SS rats of the same gender. SS-6(BN) female rats had a significantly reduced ventilatory response, similar to BN rats due primarily to a reduced tidal volume. Male SS-6(BN) rats had a significantly reduced tidal volume response to hypercapnia but a slightly increased frequency response during hypercapnia. Gene(s) on the Y chromosome may play a role in this increased frequency response in the male rats because the SS-Y(BN) hypercapnic ventilatory response involves a significantly increased frequency response. Several chromosomal substitutions slightly altered the ventilatory responses to hypoxia and exercise. However, genes on chromosomes 6 and Y of those studied are of primary importance in aspects of ventilatory control currently studied.

Consomic rat model systems for physiological genomics.

A consomic rat strain is one in which an entire chromosome is introgressed into the isogenic background of another inbred strain using marker-assisted selection. The development and physiological screening of two inbred consomic rat panels on two genetic backgrounds (44 strains) is well underway. Consomic strains enable one to assign traits and quantitative trait loci (QTL) to chromosomes by surveying the panel of strains with substituted chromosomes. They enable the rapid development of congenic strains over a narrow region and enable one to perform F2 linkage studies to positionally locate QTL on a single chromosome with a fixed genetic background. These rodent model systems overcome many of the problems encountered with segregating crosses where even if linkage is found, each individual in the cross is genetically unique and the combination of genes cannot be reproduced or studied in detail. For physiologists, consomics enable studies to be performed in a replicative or longitudinal manner to elucidate in greater detail the sequential expression of genes responsible for the observed phenotypes of these animals. They often provide the best available inbred control strains for physiological comparisons with the parental strains and they enable one to assess the impact of a causal gene region in a genome by allowing comparisons of the effect of replacement of a specific chromosome on a disease susceptible or a resistant genomic background. Consomic rat strains are proving to be a unique scientific resource that can greatly extend our understanding of genes and their role in the regulation of complex function and disease.

Drug therapy in chronic heart failure.

Chronic heart failure is widely recognised as a common and escalating problem that causes major disability and often shortens life. Diuretics and digoxin have formed the mainstay of treatment for many years. Clinical trials have demonstrated that angiotensin converting enzymes and beta-blockers, in selected patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and spironolactone may also have a role in certain individuals. Newer pharmacological approaches to the management of this complex disease are being developed, but await full evaluation.

Reactive oxygen species and molecular regulation of renal oxygenation.

It has been known since the 1940s that a gradient of renal oxygenation exists in the kidney with the lowest PO2 in the renal inner medulla under physiological conditions. Due to a low PO2 milieu in the renal medulla, the cells in this region are at constant risk of hypoxic injury. Although numerous studies have shown that renal medullary cells adapt well to low PO2, the precise mechanism mediating this adaptive response remains poorly understood. Recently, hypoxia-induced molecular adaptation in mammalian tissues or cells has been studied extensively and many studies have indicated that the molecular regulation of gene expression is importantly involved. This paper focuses on the role of a transcription factor, hypoxia-inducible factor-1 (HIF-1)-mediated molecular adaptation and explores the physiological relevance of molecular activation of HIF-1 and its target genes in the renal medulla. Given that this HIF-1-mediated action is associated with local redox status, evidence is presented to indicate that reactive oxygen species (ROS), especially superoxide (O) is importantly involved in HIF-1-mediated molecular adaptation in renal medullary cells. O degrades HIF-1alpha, an HIF-1 subunit, by activating ubiquitin-proteasome and thereby decreases the transcriptional activation of many oxygen-sensitive genes. This action of O disturbs renal medullary adaptation to low PO2 and produces renal medullary dysfunction, resulting in sodium retention and hypertension. This report also provides evidence indicating the primary source of O, enzymatic pathways for O production and activating mechanism of O production in the kidney. It is concluded that HIF-1-mediated molecular adaptation to low PO2 is of importance in the regulation of renal medullary function and that ROS may target this HIF-1-mediated medullary adaptation to damage renal function.

Referral trends of people with intellectual disabilities and psychiatric disorders.

BACKGROUND: The Specialist Mental Health Service for people with an intellectual disability (ID) and psychiatric disorder (referred to throughout this paper as 'the Service') has been in operation in south-east London for the last 18 years, during which time two local, long-stay institutions have closed. AIMS: To measure the number of referrals to the Service from 1983 to 2001 and identify trends. METHODS: Data were recorded on 752 new referrals using the assessment and information rating profile. Diagnoses according to the International Classification of Diseases (10th edition) were made by two psychiatrists. Referrals for a one off consultation or assessment, or with an IQ>70 were excluded from analysis. RESULTS: Over time more non-white clients and more clients with mild ID were referred. More referrals were made in later years, and a greater proportion came from primary care. Later referrals were also more likely to have a psychiatric diagnosis than those in earlier years. CONCLUSION: Significant trends in referrals were identified, which may be explained by various external factors.

Mapping baroreceptor function to genome: a mathematical modeling approach.

To gain information about the genetic basis of a complex disease such as hypertension, blood pressure averages are often obtained and used as phenotypes in genetic mapping studies. In contrast, direct measurements of physiological regulatory mechanisms are not often obtained, due in large part to the time and expense required. As a result, little information about the genetic basis of physiological controlling mechanisms is available. Such information is important for disease diagnosis and treatment. In this article, we use a mathematical model of blood pressure to derive phenotypes related to the baroreceptor reflex, a short-term controller of blood pressure. The phenotypes are then used in a quantitative trait loci (QTL) mapping study to identify a potential genetic basis of this controller.