Improving the hospital 'soundscape': a framework to measure individual perceptual response to hospital sounds.

Work on the perception of urban soundscapes has generated a number of perceptual models which are proposed as tools to test and evaluate soundscape interventions. However, despite the excessive sound levels and noise within hospital environments, perceptual models have not been developed for these spaces. To address this, a two-stage approach was developed by the authors to create such a model. First, semantics were obtained from listening evaluations which captured the feelings of individuals from hearing hospital sounds. Then, 30 participants rated a range of sound clips representative of a ward soundscape based on these semantics. Principal component analysis extracted a two-dimensional space representing an emotional-cognitive response. The framework enables soundscape interventions to be tested which may improve the perception of these hospital environments.

Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage.

OBJECTIVE: The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage. DESIGN: Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis. RESULTS: Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration. CONCLUSION: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.

Habituation of electrically induced readiness to gnaw.

Electrical stimulation of the hypothalamus in prairie dogs (Cynomys ludovicianus) produced a readiness to gnaw which decreased over time, exhibited spontaneous recovery, and could be dishabituated by foot shock. The response decrement was in part habituatory and could modify the interaction between a stimulation-induced readiness to gnaw and a physiologically induced hunger. Functional plasticity of stimulation-induced behavior might be accounted for, in part, by habituation.

Dejerine-Sottas disease in childhood-Genetic and sonographic heterogeneity.

Introduction: The nerve sonographic features of Dejerine-Sottas disease (DSD) have not previously been described. Methods: This exploratory cross-sectional, matched, case-control study investigated differences in nerve cross-sectional area (CSA) in children with DSD compared to healthy controls and children with Charcot-Marie-Tooth disease type 1A (CMT1A). CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with DSD, controls, and CMT1A was determined individually and within each group. Results: Five children with DSD and five age- and sex-matched controls were enrolled. Data from five age-matched children with CMT1A was also included. Group comparison showed no mean difference in nerve CSA between children with DSD and controls. Individual analysis of each DSD patient with their matched control indicated an increase in nerve CSA in three of the five children. The largest increase was observed in a child with a heterozygous PMP22 point mutation (nerve CSA fivefold larger than a control and twofold larger than a child with CMT1A). Nerve CSA was moderately increased in two children-one with a heterozygous mutation in MPZ and the other of unknown genetic etiology. Conclusions: Changes in nerve CSA on ultrasonography in children with DSD differ according to the underlying genetic etiology, confirming the variation in underlying pathobiologic processes and downstream morphological abnormalities of DSD subtypes. Nerve ultrasound may assist in the clinical phenotyping of DSD and act as an adjunct to known distinctive clinical and neurophysiologic findings of DSD subtypes. Larger studies in DSD cohorts are required to confirm these findings.

PINP: a serum biomarker of bone formation in the rat.

Serum PINP has emerged as a reliable marker of bone turnover in humans and is routinely used to monitor bone formation. However, the effects of PTH (1-34) on bone turnover have not been evaluated following short-term treatment. We present data demonstrating that PINP is an early serum biomarker in the rat for assessing bone anabolic activity in response to treatment with PTH (1-38). Rat serum PINP levels were found to increase following as few as 6 days of treatment with PTH (1-38) and these increases paralleled expression of genes associated with bone formation, as well as, later increases in BMD. Additionally, PINP levels were unaffected by treatment with an antiresorptive bisphosphonate. PINP may be used to detect PTH-induced early bone formation in the rat and may be more generally applicable for preclinical testing of potential bone anabolic drugs.

Computational and experimental models of the human torso for non-penetrating ballistic impact.

Both computational finite element and experimental models of the human torso have been developed for ballistic impact testing. The human torso finite element model (HTFEM), including the thoracic skeletal structure and organs, was created in the finite element code LS-DYNA. The skeletal structure was assumed to be linear-elastic while all internal organs were modeled as viscoelastic. A physical human surrogate torso model (HSTM) was developed using biosimulant materials and the same anthropometry as the HTFEM. The HSTM response to impact was recorded with piezoresistive pressure sensors molded into the heart, liver and stomach and an accelerometer attached to the sternum. For experimentation, the HSTM was outfitted with National Institute of Justice (NIJ) Level I, IIa, II and IIIa soft armor vests. Twenty-six ballistic tests targeting the HSTM heart and liver were conducted with 22 caliber ammunition at a velocity of 329 m/s and 9 mm ammunition at velocities of 332, 358 and 430 m/s. The HSTM pressure response repeatability was found to vary by less than 10% for similar impact conditions. A comparison of the HSTM and HTFEM response showed similar pressure profiles and less than 35% peak pressure difference for organs near the ballistic impact point. Furthermore, the peak sternum accelerations of the HSTM and HTFEM varied by less than 10% for impacts over the sternum. These models provide comparative tools for determining the thoracic response to ballistic impact and could be used to evaluate soft body armor design and efficacy, determine thoracic injury mechanisms and assist with injury prevention.

Multiwell micromechanical cantilever array reader for biotechnology.

We use a multiwell micromechanical cantilever sensor (MCS) device to measure surface stress changes induced by specific adsorption of molecules. A multiplexed assay format facilitates the monitoring of the bending of 16 MCSs in parallel. The 16 MCSs are grouped within four separate wells. Each well can be addressed independently by different analyte liquids. This enables functionalization of MCS separately by flowing different solutions through each well. In addition, each well contains a fixed reference mirror which allows measuring the absolute bending of MCS. In addition, the mirror can be used to follow refractive index changes upon mixing of different solutions. The effect of the flow rate on the MCS bending change was found to be dependent on the absolute bending value of MCS. Experiments and finite element simulations of solution exchange in wells were performed. Both revealed that one solution can be exchanged by another one after 200 microl volume has flown through. Using this device, the adsorption of thiolated DNA molecules and 6-mercapto-1-hexanol on gold surfaces was performed to test the nanomechanical response of MCS.

Using a bespoke situated digital kiosk to encourage user participation in healthcare environment design.

Involving users through participation in healthcare service and environment design is growing. Existing approaches and toolkits for practitioners and researchers are often paper based involving workshops and other more traditional design approaches such as paper prototyping. The advent of digital technology provides the opportunity to explore new platforms for user participation. This paper presents results from three studies that used a bespoke situated user participation digital kiosk, engaging 33 users in investigating healthcare environment design. The studies, from primary and secondary care settings, allowed participant feedback on each environment and proved a novel, engaging "21st century" way to participate in the appraisal of the design process. The results point toward this as an exciting and growing area of research in developing not just a new method of user participation but also the technology that supports it. Limitations were noted in terms of data validity and engagement with the device. To guide the development of user participation using similar situated digital devices, key lessons and reflections are presented.

Early warning of footpad dermatitis and hockburn in broiler chicken flocks using optical flow, bodyweight and water consumption.

Footpad dermatitis and hockburn are serious welfare and economic issues for the production of broiler (meat) chickens. The authors here describe the use of an inexpensive camera system that monitors the movements of broiler flocks throughout their lives and suggest that it is possible to predict, even in young birds, the cross-sectional prevalence at slaughter of footpad dermatitis and hockburn before external signs are visible. The skew and kurtosis calculated from the authors' camera-based optical flow system had considerably more power to predict these outcomes in the 50 flocks reported here than water consumption, bodyweight or mortality and therefore have the potential to inform improved flock management through giving farmers early warning of welfare issues. Further trials are underway to establish the generality of the results.

Structural and functional roles of the N1- and N3-protons of psi at tRNA's position 39.

Pseudouridine at position 39 (Psi(39)) of tRNA's anticodon stem and loop domain (ASL) is highly conserved. To determine the physicochemical contributions of Psi(39)to the ASL and to relate these properties to tRNA function in translation, we synthesized the unmodified yeast tRNA(Phe)ASL and ASLs with various derivatives of U(39)and Psi(39). Psi(39)increased the thermal stability of the ASL (Delta T (m)= 1.3 +/- 0.5 degrees C), but did not significantly affect ribosomal binding ( K (d)= 229 +/- 29 nM) compared to that of the unmodified ASL (K (d)= 197 +/- 58 nM). The ASL-Psi(39)P-site fingerprint on the 30S ribosomal subunit was similar to that of the unmodified ASL. The stability, ribosome binding and fingerprint of the ASL with m(1)Psi(39)were comparable to that of the ASL with Psi(39). Thus, the contribution of Psi(39)to ASL stability is not related to N1-H hydrogen bonding, but probably is due to the nucleoside's ability to improve base stacking compared to U. In contrast, substitutions of m(3)Psi(39), the isosteric m(3)U(39)and m(1)m(3)Psi(39)destabilized the ASL by disrupting the A(31)-U(39)base pair in the stem, as confirmed by NMR. N3-methylations of both U and Psi dramatically decreased ribosomal binding ( K (d)= 1060 +/- 189 to 1283 +/- 258 nM). Thus, canonical base pairing of Psi(39)to A(31)through N3-H is important to structure, stability and ribosome binding, whereas the increased stability and the N1-proton afforded by modification of U(39)to Psi(39)may have biological roles other than tRNA's binding to the ribosomal P-site.

Comparison of naturally and synthetically baited spruce beetle trapping systems in the central Rocky Mountains.

We compared naturally baited trapping systems to synthetically baited funnel traps and fallen trap trees for suppressing preoutbreak spruce beetle, Dendroctonus rufipennis Kirby, populations. Lures for the traps were fresh spruce (Picea spp.) bolts or bark sections, augmented by adding female spruce beetles to create secondary attraction. In 2003, we compared a naturally baited system ("bolt trap") with fallen trap trees and with synthetically baited funnel traps. Trap performance was evaluated by comparing total beetle captures and spillover of attacks into nearby host trees. Overall, the trap systems did not significantly differ in spruce beetle captures, although bolt traps caught 6 to 7 times more beetles than funnel traps during the first 4 wk of testing. Funnel traps with synthetic lures had significantly more spillover than either trap trees or bolt traps. The study was repeated in 2004 with modifications including an enhanced blend synthetic lure. Again, trap captures were generally similar among naturally and synthetically baited traps, but naturally baited traps had significantly less spillover. Although relatively labor-intensive, the bolt trap could be used to suppress preoutbreak beetle populations, especially when spillover is undesirable. Our work provides additional avenues for management of spruce beetles and suggests that currently used synthetic lures can be improved.

Evaluation of flagellum-related proteins FliD and FspA as subunit vaccines against Campylobacter jejuni colonisation in chickens.

Campylobacter is the leading cause of food-borne diarrhoea in humans in the developed world and consumption of contaminated poultry meat is the main source of infection. Vaccination of broilers could reduce carcass contamination and zoonotic infections. Towards this aim, we evaluated recombinant anti-Campylobacter subunit vaccines based on the flagellum-capping protein FliD and the flagellum-secreted protein FspA as they are immunogenic in chickens and the flagellum is vital for colonisation. In three studies, a recombinant FliD vaccine induced a transient but reproducible and statistically significant decrease of c. 2 log10 CFU/g in caecal colonisation levels at 49 days post-primary vaccination on the day of hatch. Levels of serum IgY specific to FliD positively correlated with caecal bacterial counts in individual birds, indicating that such antibodies may not play a role in protection. The data add to the limited repertoire of candidate antigens for the control of a key foodborne zoonosis.

'Loss of control' in alcoholics.

This study evaluates the ability of alcoholics to regulate their blood alcohol levels (BAL) within a designated range by relying primarily on interoceptive cues. Forty male alcoholics and 20 control subjects were exposed to an initial training session in which they received sufficient ethanol to maintain them within a designated BAL range over a 2 1/2-hour period. They were then exposed to two experimental sessions, one providing "overfeedback" and one "underfeedback." During each session, subjects had ten drinking decisions to make with respect to regulation of their BAL. The results indicated that alcoholics displayed greater "loss-of-control" than control subjects. This finding supported the hypothesis that alcoholics may possess a neurophysiologic feedback dysfunction that contributes to their relative inability to regulate ethanol intake.

Peripheral nerve ultrasound in pediatric Charcot-Marie-Tooth disease type 1A.

OBJECTIVE: To investigate differences in nerve cross-sectional area (CSA) as measured by peripheral nerve ultrasound in children with Charcot-Marie-Tooth disease type 1A (CMT1A) compared to healthy controls. METHODS: This was a cross-sectional, matched, case-control study. CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with CMT1A and controls at each nerve site was determined. The relationship between nerve CSA and age/body metrics, and between nerve CSA and neurologic disability in CMT1A, was also evaluated. RESULTS: Twenty-nine children with CMT1A and 29 age- and sex-matched controls were enrolled. Nerve CSA was significantly increased in children with CMT1A compared to controls (1.9- to 3.5-fold increase, p < 0.001). The increase in nerve CSA with age was disproportionately greater in those with CMT1A. Nerve CSA showed a strong positive linear correlation with age, height, and weight in both the CMT1A and control groups. Disease severity correlated with both nerve CSA and age. CONCLUSIONS: Children with CMT1A have significantly increased nerve CSA compared to controls, and the increase in nerve CSA with age is disproportionately greater in CMT1A, suggesting ongoing nerve hypertrophy throughout childhood. Nerve CSA correlates with neurologic disability. These findings demonstrate the utility of peripheral nerve ultrasound as a diagnostic tool in pediatric neuropathies, and as an outcome measure in natural history studies and clinical trials in CMT1A. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that measurement of nerve CSA by peripheral nerve ultrasound accurately identifies patients with CMT1A.

Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits.

Intermittent administration of parathyroid hormone (PTH) has an anabolic effect in cancellous bone of osteoporotic humans. However, the effect of PTH on cortical bone with Haversian remodeling remains controversial. The aim of this study was to determine the effects of biosynthetic human PTH(1-34) on the histology and mechanical properties of cortical bone in rabbits, which exhibit Haversian remodeling. Mature New Zealand white rabbits were treated with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 micrograms/kg/day or 40 micrograms/kg/day for 140 days. Body weight in rabbits treated with PTH did not change significantly over the experimental period. Serum calcium and phosphate were within the normal range, but a 1 mg/ml increase in serum calcium was observed in rabbits given the higher dose of PTH. Histomorphometry of cortical bone in the midshaft of the tibia showed significant increases in periosteal and endocortical bone formation in these rabbits. Intracortical bone remodeling in the tibia was activated and cortical porosity increased by PTH. Cross-sectional bone area and bone mass of the midshaft of the femur increased significantly after PTH treatment. Ultimate force, stiffness, and work to failure of the midshaft of the femur of rabbits given the 40 micrograms dose of PTH were significantly greater than those in the control group, whereas elastic modulus was significantly lower than that in the rabbits given the 10 micrograms dose of PTH, but not different from controls. In the third lumbar vertebra, PTH increased both formation and resorption without increasing cancellous bone volume. The increases in bone turnover and cortical porosity were accompanied by concurrent increases in bone at the periosteal and endocortical surfaces. The combination of these phenomena resulted in an enhancement of the ultimate stress, stiffness, and work to failure of the femur.

Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893.

Daily administration of parathyroid hormone (PTH) and PTH-related protein (PTHrP) peptides has been shown to increase bone mass and strength in animals and, for PTH, to increase bone mass in humans. Long-term direct comparison of multiple members of the PTH/PTHrP family in vivo has not been reported. We therefore selected three PTH/PTHrP molecules for direct comparison in vivo in an adult rat model of postmenopausal osteoporosis: PTH(1-34), PTHrP(1-36), and the PTH analog, SDZ-PTH 893 ¿Leu8, Asp10, Lys11, Ala16, Gln18, Thr33, Ala34 human PTH 1-34 [hPTH(1-34)]¿. A 6-month study was performed in which adult (6-month-old) vehicle-treated ovariectomized (OVX) and sham OVX rats were compared with OVX rats receiving 40 micrograms/kg per day of either PTH(1-34), PTHrP(1-36), or PTH-SDZ-893. Bone mass, as assessed by ash weight and densitometry, bone histomorphometry, biomechanical properties at trabecular and cortical sites, and indices of bone formation markedly increased in all three PTH/PTHrP peptide-treated groups as compared with controls. In general, this improvement followed a rank order of SDZ-PTH-893 > PTH > PTHrP. The adverse effect profile also was greatest with SDZ-PTH-893; these rats developed moderate hypercalcemia, marked renal calcium accumulation, and displayed a 13% mortality. These studies show that PTH(1-34), PTHrP(1-36), and PTH-SDZ-893 significantly and progressively increase bone mass and bone strength in this rat model of postmenopausal osteoporosis. The adverse effect profile correlates in general terms with efficacy. All three peptides show promise as skeletal anabolic agents. Further studies in humans will be required to define optimal efficacy-to-adverse effect ratios and relative efficacy for each peptide in human osteoporosis.

Comparison of recombinant human PTH(1-34) (LY333334) with a C-terminally substituted analog of human PTH-related protein(1-34) (RS-66271): In vitro activity and in vivo pharmacological effects in rats.

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are believed to exert their biological actions through binding and activation of a common cell surface receptor. Recently, an analog of PTHrP (RS-66271), was described that demonstrated reduced binding affinity for the PTH/PTHrP receptor compared with bovine PTH(1-34) but retained equal biological activity. The present study investigated the receptor binding affinities of synthetic RS-66271 and recombinant human PTH(1-34) (LY333334) and compared their in vitro and in vivo pharmacological effects. RS-66271 had one hundredth the activity of PTH(1-34) in competing for the binding of [125I] [Nle8,18, Tyr34]human PTH(1-34) to the human PTH/PTHrP receptor stably expressed in a human kidney cell line. Despite this reduced binding affinity, RS-66271 had equivalent activity in increasing both cAMP production in osteoblast-like cells and bone resorption in neonatal mouse calvariae. However, RS-66271 was 7. 6-fold less active in stimulating inositol phosphate production. For in vivo studies, young, male Fisher rats received a daily subcutaneous dose of either 10 or 40 microg/kg of peptide for 1, 2, or 4 weeks. Volumetric bone mineral density and total bone mineral content of the proximal tibia were determined by peripheral quantitative computerized tomography. Trabecular and cortical bone of the distal femur were analyzed for calcium and dry weight. Lumbar vertebrae (L4-L6) were analyzed by histomorphometry. Trabecular and cortical bone mass showed a dose- and time-dependent increase in the treated animals compared with the controls. These increases were evident as early as 1 week after initiation of dosing. There were no consistent significant differences in the comparative effects of PTH(1-34) and RS-66271 on the measured bone parameters. In conclusion, despite the reduced binding affinity of RS-66271 for the PTH/PTHrP receptor compared with human PTH(1-34), both peptides displayed similar in vitro and in vivo pharmacological effects.

Catabolic effects of continuous human PTH (1--38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation.

Continuous infusion of PTH in vivo results in active bone resorption. To investigate the molecular basis of the catabolic effect of PTH in vivo, we evaluated the role of OPG and RANKL, which are known to influence osteoclast formation and function. Weanling rats fed a calcium-free diet were parathyroidectomized and infused with PTH via an Alzet pump to examine: 1) the changes of serum-ionized calcium and osteoclast number, 2) the expression of OPG/RANKL mRNA and protein, and 3) the expression of osteoblast phenotype bone formation-associated genes such as osteoblast specific transcription factor, osteocalcin, bone sialoprotein, and type I collagen. PTH (1--38) (0.01--20 microg/100 g) continuous infusion for 1--24 h resulted in a dose-dependent increase in serum-ionized calcium in parathyroidectomized rats and a corresponding dose-dependent increase in osteoclast number, indicating an increased bone resorption. At 20 microg/100 g PTH dose level, serum-ionized calcium was 2.1-fold of the vehicle control and not different from the Sham-parathyroidectomized rats, and osteoclast number was 3-fold of the vehicle control and 1.7-fold of the Sham-parathyroidectomized rats. In the distal femur, RANKL mRNA expression was increased (27-fold) and OPG mRNA expression was decreased (4.6-fold). The changes in RANKL and OPG mRNA levels were rapid (as early as 1 h), dose dependent, and sustained over a 24-h period that was examined. Immunohistochemical evaluation of bone sections confirmed that OPG level was reduced in proximal tibial metaphysis upon PTH infusion. Circulating OPG protein level was also decreased by 32% when compared with the parathyroidectomized control. The expression of genes that mark the osteoblast phenotype was significantly decreased [osteoblast specific transcription factor (2.3-fold), osteocalcin (3-fold), bone sialoprotein (2.8-fold), and type I collagen (5-fold)]. These results suggest that the catabolic effect of PTH infusion in vivo in this well-established resorption model is associated with a reciprocal expression of OPG/RANKL and a co-ordinate decrease in the expression of bone formation-related genes. We propose that the rapid and sustained increase in RANKL and decrease in OPG initiate maintain and favor the cascade of events in the differentiation/recruitment and activation of osteoclasts.