Determinants of exercise capacity in patients with type 2 diabetes

OBJECTIVE - Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS - Subclinical left ventricular (LV) dysfunction was sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 +/- 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 +/- 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model. RESULTS - Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r- = -0.37, P < 0.001), male sex (r = 0.26, P = 0.001), BMI (r = -0.19, P = 0.012), HbA(1c) (AlC; r = -0.22, P = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration (r = -0.18, P = 0.021), and hypertension history (r = -0.28, P < 0.001). Age (P < 0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013), and AlC (P = 0.0007) were independent predictors of exercise capacity. CONCLUSIONS - Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR.

Ventilatory changes following head-up tilt and standing in healthy subjects

Passive tilting increases ventilation in healthy subjects; however, controversy surrounds the proposed mechanism. This study is aimed to evaluate the possible mechanism for changes to ventilation following passive head-up tilt (HUT) and active standing by comparison of a range of ventilatory, metabolic and mechanical parameters. Ventilatory parameters (V (T), V (E), V (E)/VO2, V (E)/VCO2, f and PetCO(2)), functional residual capacity (FRC), respiratory mechanics with impulse oscillometry; oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 20 healthy male subjects whilst supine, following HUT to 70 degrees and unsupported standing. Data were analysed using a linear mixed model. HUT to 70 degrees from supine increased minute ventilation (V (E)) (P < 0.001), tidal volume (V (T)) (P=0.001), ventilatory equivalent for O-2 (V (E)/VO2) (P=0.020) and the ventilatory equivalent for CO2 (V (E)/VCO2) (P < 0.001) with no change in f (P=0.488). HUT also increased FRC (P < 0.001) and respiratory system reactance (X5Hz) (P < 0.001) with reduced respiratory system resistance (R5Hz) (P=0.004) and end-tidal carbon dioxide (PetCO(2)) (P < 0.001) compared to supine. Standing increased V (E) (P < 0.001), V (T) (P < 0.001) and V (E)/VCO2 (P=0.020) with no change in respiratory rate (f) (P=0.065), V (E)/VO2 (P=0.543). Similar changes in FRC (P < 0.001), R5Hz (P=0.013), X5Hz (P < 0.001) and PetCO(2) (P < 0.001) compared to HUT were found. In contrast to HUT, standing increased VO2 (P=0.002) and VCO2 (P=0.048). The greater increase in V (E) in standing compared to HUT appears to be related to increased VO2 and VCO2 associated with increased muscle activity in the unsupported standing position. This has implications for exercise prescription and rehabilitation of critically ill patients who have reduced cardiovascular and respiratory reserve.

The rellationship between specific features of aphasia-friendly written material and comprehension of written material for people with aphasia: An exploratory study

Background: Written material is often inaccessible fro people with aphasia. The format of written material needs to be adapted to enable people with aphasia to read with understanding. Aims: This study aimed to further explore some issues raised in Rose, Worrall, and MacKenna (2003) concerning the effects of aphasia-friendly formats on the reading comprehension of people with aphasia. It was hypothesised that people with aphasia would comprehend significantly more paragraphs that were formatted in an aphasia-friendly manner than control paragraphs. This study also aimed to investigate if each single aspect of aphasia-friendly formatting (i.e., simplified vocabulary and syntax, large print, increased white spacem and pictures) used in isolation would result in increased comprehension compared to control paragraphs. Other aims were to compare the effect of aphasia-friendly fromatting with the effects of each single adaptation, and to investigate if the effects of aphasia-friendly formates were related to aphasia severity. Methods & Procedures: Participants with mild to moderately severe aphasia (N = 9) read a battery of 90 paragraphs and selected the best word of phrase from a choice of four to complete each paragraph. A linear mixed model (p < .05) was used to analyse the differences in reading comprehension with each paragraph fromat across three reading grade levels. Outcomes & Results: People with aphasia comprehended significantly more aphasia-friendly paragraphs than control paragraphs. They also comprehended significantly more paragraphs with each of the following single adaptations: simplified vocabulary and syntax, large ptint, and increased white spaces. Although people with aphasia tended to comprehend more paragraphs with pictures added than control paragraphs, this difference was not significant. No significant correlation between aphasia severity and the effect of aphasia-friendly formatting was found. Conclusion: This study supports the idea that aphasia-friendly formats increase the reading comprehension of people with aphasia. It suggests that adding pictures, particularly Clip Art pictures, may not significantly improve the reading the reading comprehension of people with aphasia. These findings have implications for all written communication with people with aphasia, both in the clinical setting and in the wider community. Applying these findings may enable people with aphasia to have equal access to written information and to participate in society.

Combining GIS and Expert Opinion to Model Landscapes for a Smallholder Forest Extension Program in Leyte, the Philippines

A Geographic Information System (GIS) was used to model datasets of Leyte Island, the Philippines, to identify land which was suitable for a forest extension program on the island. The datasets were modelled to provide maps of the distance of land from cities and towns, land which was a suitable elevation and slope for smallholder forestry and land of various soil types. An expert group was used to assign numeric site suitabilities to the soil types and maps of site suitability were used to assist the selection of municipalities for the provision of extension assistance to smallholders. Modelling of the datasets was facilitated by recent developments of the ArcGIS® suite of computer programs and derivation of elevation and slope was assisted by the availability of digital elevation models (DEM) produced by the Shuttle Radar Topography (SRTM) mission. The usefulness of GIS software as a decision support tool for small-scale forestry extension programs is discussed.

A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics

The conventional convection-dispersion model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver blood flow on F and Cl. The extension of this model to include nonlinear kinetics and zonal heterogeneity of the liver is not straightforward and requires numerical solution of partial differential equation, which is not available in standard nonlinear regression analysis software. In this paper, we describe an alternative compartmental model representation of hepatic disposition (including elimination). The model allows the use of standard software for data analysis and accurately describes the outflow concentration-time profile for a vascular marker after bolus injection into the liver. In an evaluation of a number of different compartmental models, the most accurate model required eight vascular compartments, two of them with back mixing. In addition, the model includes two adjacent secondary vascular compartments to describe the tail section of the concentration-time profile for a reference marker. The model has the added flexibility of being easy to modify to model various enzyme distributions and nonlinear elimination. Model predictions of F, MTT, CV2, and concentration-time profile as well as parameter estimates for experimental data of an eliminated solute (palmitate) are comparable to those for the extended convection-dispersion model.

A formal model of real-time program compilation

Program compilation can be formally defined as a sequence of equivalence-preserving transformations, or refinements, from high-level language programs to assembler code, Recent models also incorporate timing properties, but the resulting formalisms are intimidatingly complex. Here we take advantage of a new, simple model of real-time refinement, based on predicate transformer semantics, to present a straightforward compilation formalism that incorporates real-time constraints. (C) 2002 Elsevier Science B.V. All rights reserved.

Evaluation of the BEASY program using linear and piecewise linear approaches for the boundary conditions

The boundary element method (BEM) was used to study galvanic corrosion using linear and logarithmic boundary conditions. The linear boundary condition was implemented by using the linear approach and the piecewise linear approach. The logarithmic boundary condition was implemented by the piecewise linear approach. The calculated potential and current density distribution were compared with the prior analytical results. For the linear boundary condition, the BEASY program using the linear approach and the piecewise linear approach gave accurate predictions of the potential and the galvanic current density distributions for varied electrolyte conditions, various film thicknesses, various electrolyte conductivities and various area ratio of anode/cathode. The 50-point piecewise linear method could be used with both linear and logarithmic polarization curves.

Designs for generalized linear models with several variables and model uncertainty

Standard factorial designs sometimes may be inadequate for experiments that aim to estimate a generalized linear model, for example, for describing a binary response in terms of several variables. A method is proposed for finding exact designs for such experiments that uses a criterion allowing for uncertainty in the link function, the linear predictor, or the model parameters, together with a design search. Designs are assessed and compared by simulation of the distribution of efficiencies relative to locally optimal designs over a space of possible models. Exact designs are investigated for two applications, and their advantages over factorial and central composite designs are demonstrated.

A Nonstationary Model of Newborn EEG

The detection of seizure in the newborn is a critical aspect of neurological research. Current automatic detection techniques are difficult to assess due to the problems associated with acquiring and labelling newborn electroencephalogram (EEG) data. A realistic model for newborn EEG would allow confident development, assessment and comparison of these detection techniques. This paper presents a model for newborn EEG that accounts for its self-similar and non-stationary nature. The model consists of background and seizure sub-models. The newborn EEG background model is based on the short-time power spectrum with a time-varying power law. The relationship between the fractal dimension and the power law of a power spectrum is utilized for accurate estimation of the short-time power law exponent. The newborn EEG seizure model is based on a well-known time-frequency signal model. This model addresses all significant time-frequency characteristics of newborn EEG seizure which include; multiple components or harmonics, piecewise linear instantaneous frequency laws and harmonic amplitude modulation. Estimates of the parameters of both models are shown to be random and are modelled using the data from a total of 500 background epochs and 204 seizure epochs. The newborn EEG background and seizure models are validated against real newborn EEG data using the correlation coefficient. The results show that the output of the proposed models has a higher correlation with real newborn EEG than currently accepted models (a 10% and 38% improvement for background and seizure models, respectively).

A master equation model for bimolecular reaction via multi-well isomerization intermediates

A reversible linear master equation model is presented for pressure- and temperature-dependent bimolecular reactions proceeding via multiple long-lived intermediates. This kinetic treatment, which applies when the reactions are measured under pseudo-first-order conditions, facilitates accurate and efficient simulation of the time dependence of the populations of reactants, intermediate species and products. Detailed exploratory calculations have been carried out to demonstrate the capabilities of the approach, with applications to the bimolecular association reaction C3H6 + H reversible arrow C3H7 and the bimolecular chemical activation reaction C2H2 +(CH2)-C-1--> C3H3+H. The efficiency of the method can be dramatically enhanced through use of a diffusion approximation to the master equation, and a methodology for exploiting the sparse structure of the resulting rate matrix is established.

Improving wheat simulation capabilities in Australia from a cropping systems perspective - III. The integrated wheat model (I_WHEAT)

Previous work has identified several short-comings in the ability of four spring wheat and one barley model to simulate crop processes and resource utilization. This can have important implications when such models are used within systems models where final soil water and nitrogen conditions of one crop define the starting conditions of the following crop. In an attempt to overcome these limitations and to reconcile a range of modelling approaches, existing model components that worked demonstrably well were combined with new components for aspects where existing capabilities were inadequate. This resulted in the Integrated Wheat Model (I_WHEAT), which was developed as a module of the cropping systems model APSIM. To increase predictive capability of the model, process detail was reduced, where possible, by replacing groups of processes with conservative, biologically meaningful parameters. I_WHEAT does not contain a soil water or soil nitrogen balance. These are present as other modules of APSIM. In I_WHEAT, yield is simulated using a linear increase in harvest index whereby nitrogen or water limitations can lead to early termination of grainfilling and hence cessation of harvest index increase. Dry matter increase is calculated either from the amount of intercepted radiation and radiation conversion efficiency or from the amount of water transpired and transpiration efficiency, depending on the most limiting resource. Leaf area and tiller formation are calculated from thermal time and a cultivar specific phyllochron interval. Nitrogen limitation first reduces leaf area and then affects radiation conversion efficiency as it becomes more severe. Water or nitrogen limitations result in reduced leaf expansion, accelerated leaf senescence or tiller death. This reduces the radiation load on the crop canopy (i.e. demand for water) and can make nitrogen available for translocation to other organs. Sensitive feedbacks between light interception and dry matter accumulation are avoided by having environmental effects acting directly on leaf area development, rather than via biomass production. This makes the model more stable across environments without losing the interactions between the different external influences. When comparing model output with models tested previously using data from a wide range of agro-climatic conditions, yield and biomass predictions were equal to the best of those models, but improvements could be demonstrated for simulating leaf area dynamics in response to water and nitrogen supply, kernel nitrogen content, and total water and nitrogen use. I_WHEAT does not require calibration for any of the environments tested. Further model improvement should concentrate on improving phenology simulations, a more thorough derivation of coefficients to describe leaf area development and a better quantification of some processes related to nitrogen dynamics. (C) 1998 Elsevier Science B.V.

Temperature and sowing date affect the linear increase of sunflower harvest index

The linearity of daily linear harvest index (HI) increase can provide a simple means to predict grain growth and yield in field crops. However, the stability of the rate of increase across genotypes and environments is uncertain. Data from three field experiments were collated to investigate the phase of linear HI increase of sunflower (Helianthus annuus L,) across environments by changing genotypes, sowing time, N level, and solar irradiation level. Linear increase in HI was similar among different genotypes, N levels, and radiation treatments (mean 0.0125 d(-1)). but significant differences occurred between sowings, The linear increase in HI was not stable at very low temperatures (down to 9 degrees C) during grain filling, due to possible limitations to biomass accumulation and translocation (mean 0.0091 d(-1)). Using the linear increase in HI to predict grain yield requires predictions of the duration from anthesis to the onset of linear HI increase (lag phase) and the cessation of linear RT increase. These studies showed that the lag phase differed, and the linear HI increase ceased when 91% of the anthesis to physiological maturity period had been completed.

Modification of the in vivo four-point loading model for studying mechanically induced bone adaptation

We modified the noninvasive, in vivo technique for strain application in the tibiae of rats (Turner et al,, Bone 12:73-79, 1991), The original model applies four-point bending to right tibiae via an open-loop, stepper-motor-driven spring linkage, Depending on the magnitude of applied load, the model produces new bone formation at periosteal (Ps) or endocortical surfaces (Ec.S). Due to the spring linkage, however, the range of frequencies at which loads can be applied is limited. The modified system replaces this design with an electromagnetic vibrator. A load transducer in series with the loading points allows calibration, the loaders' position to be adjusted, and cyclic loading completed under load central as a closed servo-loop. Two experiments were conducted to validate the modified system: (1) a strain gauge was applied to the lateral surface of the right tibia of 5 adult female rats and strains measured at applied loads from 10 to 60 N; and (2) the bone formation response was determined in 28 adult female Sprague-Dawley rats. Loading was applied as a haversine wave with a frequency of 2 Hz for 18 sec, every second day for 10 days. Peak bending loads mere applied at 33, 40, 52, and 64 N, and a sham-loading group tr as included at 64 N, Strains in the tibiae were linear between 10 and 60 N, and the average peak strain at the Ps.S at 60 N was 2664 +/- 250 microstrain, consistent with the results of Turner's group. Lamellar bone formation was stimulated at the Ec.S by applied bending, but not by sham loading. Bending strains above a loading threshold of 40 N increased Ec Lamellar hone formation rate, bone forming surface, and mineral apposition rate with a dose response similar to that reported by Turner et al, (J Bone Miner Res 9:87-97, 1994). We conclude that the modified loading system offers precision for applied loads of between 0 and 70 N, versatility in the selection of loading rates up to 20 Hz, and a reproducible bone formation response in the rat tibia, Adjustment of the loader also enables study of mechanical usage in murine tibia, an advantage with respect to the increasing variety of transgenic strains available in bone and mineral research. (Bone 23:307-310; 1998) (C) 1998 by Elsevier Science Inc. All rights reserved.

Epidermal iontophoresis: II. Application of the ionic mobility-pore model to the transport of local anesthetics

Purpose, An in vitro study was carried out to determine the iontophoretic permeability of local anesthetics through human epidermis. The relationship between physicochemical structure and the permeability of these solutes was then examined using an ionic mobility-pore model developed to define quantitative relationships. Methods. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetracaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine, bupivacaine, etidocaine, cinchocaine) were determined through excised human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivity measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the ionic mobility-pore model and to determine the best predictor of iontophoretic permeability of the local anesthetics. Results. The logarithm of the iontophoretic permeability coefficient (log PCj,iont) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held constant. Multiple linear regressions confirmed that log PCj,iont was best defined by ionic mobility (and its determinants: conductivity, pK(a) and MW) and MW. Conclusions. Our results suggest that of the properties studied, the best predictors of iontophoretic transport of local anesthetics are ionic mobility (or pK(a)) and molecular size. These predictions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epidermal permselectivity and other factors as defined by the model.