Synthesis of a heparan sulfate mimetic disaccharide with a conformationally locked residue from a common intermediate

A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy--D-glucose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.

Maintaining nutrition in aged care residents with a train-the-trainer intervention and nutrition coordinator

Objective: To investigate the impact of a train-the-trainer program on the nutritional status of older people in residential care. ----- Design: Prospective, randomized controlled study. Setting: Eight nursing homes in Southeast Queensland, Australia. ----- Participants: A total of 352 residents participated - 245 were female (69.6%). The mean age was 84.2 years and the majority (79.4%) were classified as high dependency. ----- Intervention: Residents from four nursing homes were randomly selected for a nutrition education program coordinated by Nutrition Coordinators. Residents from the other four nursing homes (control) received usual care. ----- Measurements: The Subjective Global Assessment was used to determine prevalence of malnutrition at baseline and six months post intervention. The Resident Classification Scale measured functional dependency. Prescribed diet, fluids, oral hygiene status and allied health referrals were obtained by chart audit. ----- Results: Approximately half the residents were well nourished with 49.4% moderately or severely malnourished. Residents in the intervention group were more likely to maintain or improve their nutritional status compared with the control group who were more likely to experience a deterioration (P=0.027). The odds of the control group being malnourished post test was 1.6 times more likely compared with the intervention group but this did not reach statistical significance (P=0.1). ----- Conclusion: The results of the study encourage the implementation of a Nutrition Coordinator program to maintain nutritional status of aged care residents. Nevertheless, malnutrition rates continue to be unacceptably high. In a rapidly aging society, the aged care sector needs to confront malnutrition and provide better resources for staff to take measures against this problem.

Improved image contrast of the bone-muscle interface with 3T MRI compared to 1.5T MRI [Abstract]

Virtual 3D models of long bones are increasingly being used for implant design and research applications. The current gold standard for the acquisition of such data is Computed Tomography (CT) scanning. Due to radiation exposure, CT is generally limited to the imaging of clinical cases and cadaver specimens. Magnetic Resonance Imaging (MRI) does not involve ionising radiation and therefore can be used to image selected healthy human volunteers for research purposes. The feasibility of MRI as alternative to CT for the acquisition of morphological bone data of the lower extremity has been demonstrated in recent studies [1, 2]. Some of the current limitations of MRI are long scanning times and difficulties with image segmentation in certain anatomical regions due to poor contrast between bone and surrounding muscle tissues. Higher field strength scanners promise to offer faster imaging times or better image quality. In this study image quality at 1.5T is quantitatively compared to images acquired at 3T. --------- The femora of five human volunteers were scanned using 1.5T and 3T MRI scanners from the same manufacturer (Siemens) with similar imaging protocols. A 3D flash sequence was used with TE = 4.66 ms, flip angle = 15° and voxel size = 0.5 × 0.5 × 1 mm. PA-Matrix and body matrix coils were used to cover the lower limb and pelvis respectively. Signal to noise ratio (SNR) [3] and contrast to noise ratio (CNR) [3] of the axial images from the proximal, shaft and distal regions were used to assess the quality of images from the 1.5T and 3T scanners. The SNR was calculated for the muscle and bone-marrow in the axial images. The CNR was calculated for the muscle to cortex and cortex to bone marrow interfaces, respectively. --------- Preliminary results (one volunteer) show that the SNR of muscle for the shaft and distal regions was higher in 3T images (11.65 and 17.60) than 1.5T images (8.12 and 8.11). For the proximal region the SNR of muscles was higher in 1.5T images (7.52) than 3T images (6.78). The SNR of bone marrow was slightly higher in 1.5T images for both proximal and shaft regions, while it was lower in the distal region compared to 3T images. The CNR between muscle and bone of all three regions was higher in 3T images (4.14, 6.55 and 12.99) than in 1.5T images (2.49, 3.25 and 9.89). The CNR between bone-marrow and bone was slightly higher in 1.5T images (4.87, 12.89 and 10.07) compared to 3T images (3.74, 10.83 and 10.15). These results show that the 3T images generated higher contrast between bone and the muscle tissue than the 1.5T images. It is expected that this improvement of image contrast will significantly reduce the time required for the mainly manual segmentation of the MR images. Future work will focus on optimizing the 3T imaging protocol for reducing chemical shift and susceptibility artifacts.

The effect of graded levels of exercise on energy intake and balance in free-living men, consuming their normal diet

Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ~1.6 MJ/day) and high exercise level (Hex; ~3.2 MJ/day). On days 1-2 subjects were given a medium fat (MF) maintenance diet (1.6 ´ resting metabolic rate (RMR)). Measurements: On days 3-9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P<0.001 (s.e.d=0.55)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 11.6, 11.8 and 11.8 MJ/day (F(2,10)=0.10; P=0.910 (s.e.d.=0.10)), respectively. There were no treatment effects on hunger, appetite or body weight, but there was evidence of weight loss on the Hex treatment. Conclusion: Increasing EE did not lead to compensation of EI over 7 days. However, total daily EE tended to decrease over time on the two exercise treatments. Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI.

Coding speech signals at very low rates (below 1 kb/s) with high intelligibility

This thesis presents an original approach to parametric speech coding at rates below 1 kbitsjsec, primarily for speech storage applications. Essential processes considered in this research encompass efficient characterization of evolutionary configuration of vocal tract to follow phonemic features with high fidelity, representation of speech excitation using minimal parameters with minor degradation in naturalness of synthesized speech, and finally, quantization of resulting parameters at the nominated rates. For encoding speech spectral features, a new method relying on Temporal Decomposition (TD) is developed which efficiently compresses spectral information through interpolation between most steady points over time trajectories of spectral parameters using a new basis function. The compression ratio provided by the method is independent of the updating rate of the feature vectors, hence allows high resolution in tracking significant temporal variations of speech formants with no effect on the spectral data rate. Accordingly, regardless of the quantization technique employed, the method yields a high compression ratio without sacrificing speech intelligibility. Several new techniques for improving performance of the interpolation of spectral parameters through phonetically-based analysis are proposed and implemented in this research, comprising event approximated TD, near-optimal shaping event approximating functions, efficient speech parametrization for TD on the basis of an extensive investigation originally reported in this thesis, and a hierarchical error minimization algorithm for decomposition of feature parameters which significantly reduces the complexity of the interpolation process. Speech excitation in this work is characterized based on a novel Multi-Band Excitation paradigm which accurately determines the harmonic structure in the LPC (linear predictive coding) residual spectra, within individual bands, using the concept 11 of Instantaneous Frequency (IF) estimation in frequency domain. The model yields aneffective two-band approximation to excitation and computes pitch and voicing with high accuracy as well. New methods for interpolative coding of pitch and gain contours are also developed in this thesis. For pitch, relying on the correlation between phonetic evolution and pitch variations during voiced speech segments, TD is employed to interpolate the pitch contour between critical points introduced by event centroids. This compresses pitch contour in the ratio of about 1/10 with negligible error. To approximate gain contour, a set of uniformly-distributed Gaussian event-like functions is used which reduces the amount of gain information to about 1/6 with acceptable accuracy. The thesis also addresses a new quantization method applied to spectral features on the basis of statistical properties and spectral sensitivity of spectral parameters extracted from TD-based analysis. The experimental results show that good quality speech, comparable to that of conventional coders at rates over 2 kbits/sec, can be achieved at rates 650-990 bits/sec.

Randomized trial of effect of bifocal and prismatic bifocal spectacles on myopic progression

Objective: To determine whether bifocal and prismatic bifocal spectacles could control myopia in children with high rates of myopic progression. ---------- Methods: This was a randomized controlled clinical trial. One hundred thirty-five (73 girls and 62 boys) myopic Chinese Canadian children (myopia of 1.00 diopters [D]) with myopic progression of at least 0.50 D in the preceding year were randomly assigned to 1 of 3 treatments: (1) single-vision lenses (n = 41), (2) +1.50-D executive bifocals (n = 48), or (3) +1.50-D executive bifocals with a 3–prism diopters base-in prism in the near segment of each lens (n = 46). ---------- Main Outcome Measures: Myopic progression measured by an automated refractor under cycloplegia and increase in axial length (secondary) measured by ultrasonography at 6-month intervals for 24 months. Only the data of the right eye were used. ---------- Results: Of the 135 children (mean age, 10.29 years [SE, 0.15 years]; mean visual acuity, –3.08 D [SE, 0.10 D]), 131 (97%) completed the trial after 24 months. Myopic progression averaged –1.55 D (SE, 0.12 D) for those who wore single-vision lenses, –0.96 D (SE, 0.09 D) for those who wore bifocals, and –0.70 D (SE, 0.10 D) for those who wore prismatic bifocals. Axial length increased an average of 0.62 mm (SE, 0.04 mm), 0.41 mm (SE, 0.04 mm), and 0.41 mm (SE, 0.05 mm), respectively. The treatment effect of bifocals (0.59 D) and prismatic bifocals (0.85 D) was significant (P < .001) and both bifocal groups had less axial elongation (0.21 mm) than the single-vision lens group (P < .001). ---------- Conclusions: Bifocal lenses can moderately slow myopic progression in children with high rates of progression after 24 months.

Randomised controlled trial of an automated, interactive telephone intervention to improve type 2 diabetes self-management (Telephone-Linked Care Diabetes Project) : study protocol

Background: An estimated 285 million people worldwide have diabetes and its prevalence is predicted to increase to 439 million by 2030. For the year 2010, it is estimated that 3.96 million excess deaths in the age group 20-79 years are attributable to diabetes around the world. Self-management is recognised as an integral part of diabetes care. This paper describes the protocol of a randomised controlled trial of an automated interactive telephone system aiming to improve the uptake and maintenance of essential diabetes self-management behaviours. ---------- Methods/Design: A total of 340 individuals with type 2 diabetes will be randomised, either to the routine care arm, or to the intervention arm in which participants receive the Telephone-Linked Care (TLC) Diabetes program in addition to their routine care. The intervention requires the participants to telephone the TLC Diabetes phone system weekly for 6 months. They receive the study handbook and a glucose meter linked to a data uploading device. The TLC system consists of a computer with software designed to provide monitoring, tailored feedback and education on key aspects of diabetes self-management, based on answers voiced or entered during the current or previous conversations. Data collection is conducted at baseline (Time 1), 6-month follow-up (Time 2), and 12-month follow-up (Time 3). The primary outcomes are glycaemic control (HbA1c) and quality of life (Short Form-36 Health Survey version 2). Secondary outcomes include anthropometric measures, blood pressure, blood lipid profile, psychosocial measures as well as measures of diet, physical activity, blood glucose monitoring, foot care and medication taking. Information on utilisation of healthcare services including hospital admissions, medication use and costs is collected. An economic evaluation is also planned.---------- Discussion: Outcomes will provide evidence concerning the efficacy of a telephone-linked care intervention for self-management of diabetes. Furthermore, the study will provide insight into the potential for more widespread uptake of automated telehealth interventions, globally.

Intake of isoflavone and lignan phytoestrogens and associated demographic and lifestyle factors in older Australian women

The purpose was to determine intake of phytoestrogens in a sample of older Australian women, and to investigate associated lifestyle factors. Subjects were an age-stratified sample of 511 women aged 40-80 y, randomly selected from the electoral roll and participating in the Longitudinal Assessment of Ageing in Women at the Royal Brisbane and Women’s Hospital. A cross-sectional study was conducted to assess isoflavone and lignan intake over the past month from food and supplements using a 112-item phytoestrogen frequency questionnaire. Data were also collected on nutrient intakes, physical activity, smoking, alcohol, non-prescription supplements, hormone therapy, education and occupation. Logistic regression was used to evaluate associations between demographic and lifestyle variables and soy/linseed consumption while controlling for age. Isoflavone intakes were significantly higher in the younger compared to older age groups (p<0.001); there were no age-related differences in lignan intake. Forty-five percent of women consumed at least one serve of a soy and/or linseed item and were defined as a soy/linseed consumer. Median (range) intakes by consumers for isoflavones and lignans (3.9 (0-172) mg/d and 2.4 (0.1-33) mg/d) were higher than intakes by non-consumers (0.004 (0-2.6) mg/d and 1.57 (0.44-4.7) mg/d), respectively (p<0.001). Consumers had higher intakes of dietary fibre (p=0.003), energy (p=0.04) and polyunsaturated fat (p=0.004), and higher levels of physical activity (p=0.006), socio-economic position (p<0.001), education (p<0.001) and supplement use (p<0.001). Women who consumed soy or linseed foods differed in lifestyle and demographic characteristics suggesting these factors should be considered when investigating associations with chronic disease outcomes.

Channel plasmon-polariton modes in V grooves filled with dielectric

We investigated the effect of dielectric filling in a V groove on the propagation parameters of channel plasmon-polariton (CPP) modes. In particular, existence conditions and critical groove angles, mode localization, field structure, dispersion, and propagation distances of CPP modes are analyzed as functions of dielectric permittivity inside the groove. It is demonstrated that increasing dielectric permittivity in the groove results in a rapid increase of mode localization near the tip of the groove and increase of both the critical angles that determine a range of groove angles for which CPP modes can exist. Detailed analysis of the field structure has demonstrated that the maximum of the field in a CPP mode is typically reached at a small distance from the tip of the groove. The effect of rounded tip is also investigated.

Characteristics of airborne ultrafine and coarse particles during the Australian dust storm of 23 September 2009

Particle number concentrations and size distributions, visibility and particulate mass concentrations and weather parameters were monitored in Brisbane, Australia, on 23 September 2009, during the passage of a dust storm that originated 1400 km away in the dry continental interior. The dust concentration peaked at about mid-day when the hourly average PM2.5 and PM10 values reached 814 and 6460 µg m-3, respectively, with a sharp drop in atmospheric visibility. A linear regression analysis showed a good correlation between the coefficient of light scattering by particles (Bsp) and both PM10 and PM2.5. The particle number in the size range 0.5-20 µm exhibited a lognormal size distribution with modal and geometrical mean diameters of 1.6 and 1.9 µm, respectively. The modal mass was around 10 µm with less than 10% of the mass carried by particles smaller than 2.5 µm. The PM10 fraction accounted for about 68% of the total mass. By mid-day, as the dust began to increase sharply, the ultrafine particle number concentration fell from about 6x103 cm-3 to 3x103 cm-3 and then continued to decrease to less than 1x103 cm-3 by 14h, showing a power-law decrease with Bsp with an R2 value of 0.77 (p<0.01). Ultrafine particle size distributions also showed a significant decrease in number during the dust storm. This is the first scientific study of particle size distributions in an Australian dust storm.

Myoinositol Abnormalities in Temporal Lobe Epilepsy

Purpose: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. Methods: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. Results: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 ± 1.9 mM, control NA, 9.2 ± 1.3 mM; p < 0.05; HS-TLE MI, 6.1 ± 1.6 mM, control mI 4.9 ± 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 ± 0.8 mM; p < 0.05; HS-TLE, 3.6 ±.05 mM; p < 0.001; controls, 4.8 ± 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 ± 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 ± 0.8 mM; p < 0.05). Conclusions: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.

Innovative planning approaches for generator interconnection group study

Today, a large number of wind generator interconnection requests have been queued and are being processed. The generator interconnection group study is a way to reduce the generator interconnection cycle time and increase interconnection certainty. However, it is very challenging to identify the “best” transmission upgrades for a large group of generator interconnections. It is also very important to differentiate the constraints caused by each generator interconnection request and identify their responsibilities for transmission upgrades. This paper outlines some innovative study approaches that can be used in a group study with large numbers of generator interconnection requests in a constrained area. Improved study methods are introduced, and a summary and conclusions are derived from the study.

Akt, AS160, metabolic risk factors and aerobic fitness in middle-aged women

Aims: This study investigated the association between the basal (rest) insulin-signaling proteins, Akt, and the Akt substrate AS160, metabolic risk factors, inflammatory markers and aerobic fitness, in middle-aged women with varying numbers of metabolic risk factors for type 2 diabetes. Methods: Sixteen women (n = 16) aged 51.3+/-5.1 (mean +/-SD) years provided muscle biopsies and blood samples at rest. In addition, anthropometric characteristics and aerobic power were assessed and the number of metabolic risk factors for each participant was determined (IDF criteria). Results: The mean number of metabolic risk factors was 1.6+/-1.2. Total Akt was negatively correlated with IL-1 beta (r = -0.45, p = 0.046), IL-6 (r = -0.44, p = 0.052) and TNF-alpha (r = -0.51, p = 0.025). Phosphorylated AS160 was positively correlated with HDL (r = 0.58, p = 0.024) and aerobic fitness (r = 0.51, p = 0.047). Furthermore, a multiple regression analysis revealed that both HDL (t = 2.5, p = 0.032) and VO(2peak) (t = 2.4, p = 0.037) were better predictors for phosphorylated AS160 than TNF-alpha or IL-6 (p>0.05). Conclusions: Elevated inflammatory markers and increased metabolic risk factors may inhibit insulin-signaling protein phosphorylation in middle-aged women, thereby increasing insulin resistance under basal conditions. Furthermore, higher HDL and fitness levels are associated with an increased AS160 phosphorylation, which may in turn reduce insulin resistance.

Drugs and the respiratory system

17.1 Drugs for bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD) 17.1.1 Introduction to asthma 17.1.2 Introduction to COPD 17.1.3 Drug delivery by inhalation 17.1.4 Drugs to treat 17.1.4.1 β2-adrenoceptor agonists 17.1.4.2 Muscarinic receptor antagonists 17.1.4.3 Leukotriene receptor antagonists 17.1.4.4 Theophylline 17.1.4.5 Oxygen for COPD 17.1.5 Drugs to prevent asthma 31.5.1 Glucocorticoids 31.5.2 Cromolyn sodium 17.1.6 Combination to treat and prevent asthma 17.1.7 Drug for allergic asthma – omalizumab 17.1.8 Emergency treatment of asthma 17.2. Expectorants, mucolytics, cough and oxygen 17.2.1 Introduction to expectorants and mucolytics 17.2.2 Expectorants 17.2.3 Mucolytics 17.2.4 Cough 17.2.5 Oxygen 17.3. Drugs for rhinitis and rhinorrea 17.3.1 Introduction 17.3.2 Histamine and H1-receptor antagonists 17.3.3 Sympathomimetic 17.3.4 Muscarinic receptor antagonists 17.3.4 Cromolyn sodium 17.3.5 Glucocorticoids