Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

Rationale  The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective  The objective of the study was to use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods  Rats were trained for NSA during daily 23-h sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results  Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23-h sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions  These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans.     

Why have meta‐analyses of randomized controlled trials of the association between non‐white‐blood‐cell‐reduced allogeneic blood transfusion and postoperative infection produced discordant results?

Intention-to-treat analyses of randomized controlled trials (RCTs) of the association between non-white-blood-cell (WBC)-reduced allogeneic blood transfusion (ABT) and postoperative infection were reported as the reason why meta-analyses of RCTs of this association have produced discordant results. We examined three possible reasons for disagreements between meta-analyses: (i) sources of medical heterogeneity and integration of RCTs despite extreme heterogeneity; (ii) reliance on as-treated (vs. intention-to-treat) comparisons; and (iii) inclusion (or not) of the three most recent RCTs. When nine RCTs reported up to 2002 were combined despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found an association between non-WBC-reduced ABT and postoperative infection [summary odds ratio (OR) = 1.38, 95% confidence interval (CI) 1.03-1.85, P < 0.05; and summary OR = 1.56, 95% CI 1.06-2.31, P < 0.05, respectively]. When 12 RCTs reported up to 2005 were integrated despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found no association of non-WBC-reduced ABT with postoperative infection (summary OR = 1.24, 95% CI 0.98-1.56, P > 0.05; and summary OR = 1.31, 95% CI 0.98-1.75, P > 0.05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non-WBC-reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage-filtered RBCs showed no association, whether intention-to-treat or as-treated comparisons were used. Thus, the published meta-analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention-to-treat and as-treated comparisons produced concordant results.     

Preserved Windkessel function in patients following reduction aortoplasty of the ascending aorta

Objective: Reduction ascending aortoplasty (RAA) is a controversial procedure. Agreement has not yet been made regarding the indication for surgery and surgical technique. The goal of this study was to examine the long‐term outcome of RAA without external support, and to compare the accuracy of transthoracic echocardiographic with computed tomographic (CT) measurements. Of particular interest was whether the important elastic properties of the aorta, the Windkessel function, is preserved following reduction aortoplasty of the ascending aorta without external wrapping. Methods: Ninety‐eight patients with dilation of the ascending aorta underwent reduction aortoplasty with concomitant cardiac procedures. Fifty‐four patients were available for follow‐up. Measurement of the ascending aortic diameter was performed prior to and directly following surgery, and 37 months postoperatively (range: 10–96 months). Both echocardiography and CT imaging were performed. The elastic properties of the ascending aorta were determined by measuring the distension of the ascending aorta during diastole and systole by means of transthoracic echocardiography. Fifteen patients with graft replacement of the ascending aorta were examined, and the control group contained 11 healthy volunteers. Results: The diameter of the ascending aorta was significantly reduced in all patients who had undergone RAA. The change in diameter between diastole and systole was 3 mm in patients with reduction aortoplasty. Patients with graft replacement had a change of only 0.07 cm. There was no relevant increase (2 mm) in diameter at follow‐up. Echocardiographic and CT measurements of the aortic diameter did not differ. Conclusions: RAA without external wrapping shows good long‐term results in patients with a dilated ascending aorta who underwent concomitant cardiac procedures. Echocardiography is very accurate in measuring the ascending aortic diameter, which makes it a cost‐effective diagnostic tool. Moreover, ascending aortoplasty without external wrapping preserves the important elastic properties, namely the Windkessel function. Follow‐up of the cardiac function and aortic diameter can be performed easily and precisely in the outpatient setting.     

A new anatomically based protocol for gait analysis in children

Human movement analysis still suffers from the weakness of the currently used protocols for data collection and reduction. Reliable data comparisons and precise functional assessment require anatomically based definitions of the reference axes and frames, and therefore careful identification and tracking of the landmarks. When impaired children are analysed, the marker-set and other measurement procedures have to be minimised to reduce the time of the experiment and ensure patient collaboration. A new protocol is proposed for the analysis of pelvis and lower limb motion obtained as a compromise between these two requirements.

A marker-set is proposed which involves the attachment of 22 skin markers, the calibration by a pointer of 6 anatomical landmarks, and the identification of the hip joint centre by a prediction approach. Anatomical reference frames and joint rotations are defined according to current recommendations. The protocol was assessed by analysing a single child in several repetitions by different examiners, and a population of 10 healthy children, mean age 9.7-years-old. The entire analysis was repeated after subtraction of the offset by static posture angles. The minimum and maximum means of the standard deviations from five examiners of the same child were respectively 2.1° in pelvic obliquity and 6.8° in knee rotation. The minimum and maximum means of the standard deviations from the 10 healthy children were 2.1° in pelvic obliquity and 9.6° in knee internal–external rotation. The protocol is feasible and allows 3D anatomical-based measurements of segment and joint motion and data sharing according to current standards.     

Fast CT metal artefacts correction based on derivative and region-based filling

Introduction: Metal artefacts seriously degrade the quality of the CT images. Blurring around the junctions between metal and non‐metal regions in CT images, metal artefacts often prevent right diagnoses, and even lead to misdiagnoses of patients. The aim of the study was to devise a fast and robust method to improve the quality of the artefact‐contaminated CT images. Methods: The proposed artefact correction includes the following five steps: metal object segmentation, forward projection, region‐based filling, adaptive scaling and final image reconstruction. Results: The feasibility of the proposed method in correcting metal artefacts was validated by experiments on both simulated and clinical images. Experiments showed the proposed correction could lead to fast and effective reduction of metal artefacts in CT images. Conclusions: Compared with other methods, the proposed method has less computational cost and allows a feasible and easy implantation into current CT imaging systems.