Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi

Limited data address the impact of HIV co-infection on the pharmacokinetics of anti-tuberculosis drugs in Sub-Saharan Africa. 47 Malawian adults underwent rich pharmacokinetic sampling at 0-0.5-1-2-3-4-6-8 and 24 hours post-dose. 51% were male; mean age was 34 years. 65% were HIV-positive with a mean CD4 count of 268 cells/μL. Anti-tuberculosis drugs were administered as fixed-dose combinations (rifampicin150mg/isoniazid75mg/pyrazinamide400mg/ethambutol275mg) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampicin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analysed by non-compartmental methods and analysis of variance of log-transformed summary parameters. Pharmacokinetic parameters were: rifampicin Cmax 4.129 (2.474-5.596)μg/mL, AUC0-24 21.32 (13.57-28.60)μg/mL*h, half-life 2.45 (1.86-3.08)h; isoniazid Cmax 3.97 (2.979-4.544)μg/mL, AUC0-24 22.5 (14.75-34.59)μg/mL*h, half-life 3.93 (3.18-4.73)h.; pyrazinamide Cmax 34.21 (30.00-41.60)μg/mL, AUC0-24 386.6 (320.0-463.7)μg/mL*h, half-life 6.821 (5.71-8.042)h; ethambutol Cmax 2.278 (1.694-3.098)μg/mL, AUC0-24 20.41 (16.18-26.27)μg/mL*h, half-life 7.507 (6.517-8.696)h. Isoniazid PK data analysis suggested that around two-thirds were slow acetylators. Dose, weight and weight-adjusted dose were not significant predictors of PK exposure probably due to weight-banded dosing. In this first pharmacokinetic study of tuberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with other studies for all first line drugs except for rifampicin, for which Cmax and AUC0-24 were notably lower. Contrary to some earlier observations, HIV status did not significantly affect AUC of any of the drugs. Increasing the dose of rifampicin could be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in half-life of isoniazid of 41% (p=0.022). Possible competitive interactions between isoniazid and sulphamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further

Three-dimensional reconstruction of myocardial contrast perfusion from biplane cineangiograms by means of linear programming techniques

The assessment of coronary flow reserve from the instantaneous distribution of the contrast agent within the coronary vessels and myocardial muscle at the control state and at maximal flow has been limited by the superimposition of myocardial regions of interest in the two-dimensional images. To overcome these limitations, we are in the process of developing a three-dimensional (3D) reconstruction technique to compute the contrast distribution in cross sections of the myocardial muscle from two orthogonal cineangiograms. To limit the number of feasible solutions in the 3D-reconstruction space, the 3D-geometry of the endo- and epicardial boundaries of the myocardium must be determined. For the geometric reconstruction of the epicardium, the centerlines of the left coronary arterial tree are manually or automatically traced in the biplane views. Next, the bifurcations are detected automatically and matched in these two views, allowing a 3D-representation of the coronary tree. Finally, the circumference of the left ventricular myocardium in a selected cross section can be computed from the intersection points of this cross section with the 3D coronary tree using B-splines. For the geometric reconstruction of the left ventricular cavity, we envision to apply the elliptical approximation technique using the LV boundaries defined in the two orthogonal views, or by applying more complex 3D-reconstruction techniques including densitometry. The actual 3D-reconstruction of the contrast distribution in the myocardium is based on a linear programming technique (Transportation model) using cost coefficient matrices. Such a cost coefficient matrix must contain a maximum amount of a priori information, provided by a computer generated model and updated with actual data from the angiographic views. We have only begun to solve this complex problem. However, based on our first experimental results we expect that the linear programming approach with advanced cost coefficient matrices and computed model will lead to a

Lower trunk motion and speed-dependence during walking

Abstract Background There is a limited understanding about how gait speed influences the control of upper body motion during walking. Therefore, the primary purpose of this study was to examine how gait speed influences healthy individual's lower trunk motion during overground walking. The secondary purpose was to assess if Principal Component Analysis (PCA) can be used to gain further insight into postural responses that occur at different walking speeds. Methods Thirteen healthy subjects (23 ± 3 years) performed 5 straight-line walking trials at self selected slow, preferred, and fast walking speeds. Accelerations of the lower trunk were measured in the anterior-posterior (AP), vertical (VT), and mediolateral (ML) directions using a triaxial accelerometer. Stride-to-stride acceleration amplitude, regularity and repeatability were examined with RMS acceleration, Approximate Entropy and Coefficient of Multiple determination respectively. Coupling between acceleration directions were calculated using Cross Approximate Entropy. PCA was used to reveal the dimensionality of trunk accelerations during walking at slow and preferred speeds, and preferred and fast speeds. Results RMS acceleration amplitude increased with gait speed in all directions. ML and VT trunk accelerations had less signal regularity and repeatability during the slow compared to preferred speed. However, stride-to-stride acceleration regularity and repeatability did not differ between the preferred and fast walking speed conditions, partly due to an increase in coupling between frontal plane accelerations. The percentage of variance accounted for by each trunk acceleration Principal Component (PC) did not differ between grouped slow and preferred, and preferred and fast walking speed acceleration data. Conclusion The main finding of this study was that walking at speeds slower than preferred primarily alters lower trunk accelerations in the frontal plane. Despite greater amplitudes of trunk acceleration at fast speeds, the lack of regularity and repeatability differences between preferred and fast speeds suggest that features of trunk motion are preserved between the same conditions. While PCA indicated that features of trunk motion are preserved between slow and preferred, and preferred and fast speeds, the discriminatory ability of PCA to detect speed-dependent differences in walking patterns is limited compared to measures of signal regularity, repeatability, and coupling.</p

Physical Activity After Surgery for Severe Obesity: The Role of Exercise Cognitions

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Physical activity after bariatric surgery is associated with sustained weight loss and improved quality of life. Some bariatric patients engage insufficiently in physical activity. This may be due to exercise cognitions, i.e., specific beliefs about benefits of and barriers to physical exercise. The aim of this study was to examine whether and to what extent both physical activity and exercise cognitions changed at 1 and 2 years post-surgery and whether exercise cognitions predict physical activity. Methods Forty-two bariatric patients (38 women, 4 men; mean age 38±8 years, mean body mass index prior to surgery 47±6 kg/m 2) filled out self-report instruments to examine physical activity and exercise cognitions pre- and post-surgery

A unified treatment of single component replacement models

In this paper we discuss a general framework for single component replacement models. This framework is based on the regenerative structure of these models and by using results from renewal theory a unified presentation of the discounted and average finite and infinite horizon cost models is given. Finally, some well-known replacement models are discussed, and making use of the previous results an easy derivation of their cost functions is presented

The second data release of the INT Photometric Ha Survey of the Northern Galactic Plane (IPHAS DR2)

The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800 deg2 imaging survey covering Galactic latitudes |b| < 5° and longitudes ℓ = 30°–215° in the r, i, and Hα filters using the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) in La Palma. We present the first quality-controlled and globally calibrated source catalogue derived from the survey, providing single-epoch photometry for 219 million unique sources across 92 per cent of the footprint. The observations were carried out between 2003 and 2012 at a median seeing of 1.1 arcsec (sampled at 0.33 arcsec pixel−1) and to a mean 5σ depth of 21.2 (r), 20.0 (i), and 20.3 (Hα) in the Vega magnitude system. We explain the data reduction and quality control procedures, describe and test the global re-calibration, and detail the construction of the new catalogue. We show that the new calibration is accurate to 0.03 mag (root mean square) and recommend a series of quality criteria to select accurate data from the catalogue. Finally, we demonstrate the ability of the catalogue's unique (r − Hα, r − i) diagram to (i) characterize stellar populations and extinction regimes towards different Galactic sightlines and (ii) select and quantify Hα emission-line objects. IPHAS is the first survey to offer comprehensive CCD photometry of point sources across the Galactic plane at visible wavelengths, providing the much-needed counterpart to recent infrared surveys

The GRONORUN 2 study: effectiveness of a preconditioning program on preventing running related injuries in novice runners. The design of a randomized controlled trial

Background: Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. Methods/Design: The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event. During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. Discussion: The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners