Body fat changes among antiretroviral-naive patients on PI- and NNRTI-based HAART in the Swiss HIV cohort study

BACKGROUND: Body fat changes are common in patients with HIV. For patients on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), these changes have been associated with increasing exposure to therapy in general and to stavudine in particular. Our objective is to show whether such associations are more or less likely for patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. METHODS: We included all antiretroviral-naive patients in the Swiss HIV Cohort Study starting HAART after April 2000 who had had body weight, CD4 cell count and plasma HIV RNA measured between 6 months before and 3 months after starting HAART, and at least one assessment of body fat changes after starting HAART. At visits scheduled every 6 months, fat loss or fat gain is reported by agreement between patient and physician. We estimate the association between reported body fat changes and both time on therapy and time on stavudine, using conditional logistical regression. RESULTS: Body fat changes were reported for 85 (9%) out of 925 patients at their first assessment; a further 165 had only one assessment. Of the remaining 675 patients, body fat changes were reported for 156 patients at a rate of 13.2 changes per 100 patient-years. Body fat changes are more likely with increasing age [odds ratio (OR) 1.18 (1.00-1.38) per 10 years], with increasing BMI [OR 1.06 (1.01-1.11)] and in those with a lower baseline CD4 cell count [OR 0.91 (0.83-1.01) per 100 cells/microl]. There is only weak evidence that body fat changes are more likely with increasing time on HAART [OR 1.16 (0.93-1.46)]. After adjusting for time on HAART, fat loss is more likely with increasing stavudine use [OR 1.70 (1.34-2.15)]. There is no evidence of an association between reported fat changes and time on NNRTI therapy relative to PI therapy in those patients who used either one therapy or the other [OR 0.98 (0.56-1.63)]. CONCLUSION: Fat loss is more likely to be reported with increasing exposure to stavudine. We find no evidence of major differences between PI and NNRTI therapy in the risk of reported body fat changes.

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.

The Appellate Body Approach to the Applicability of Article XX GATT In the Light of China - Raw Materials: A Missed Opportunity?

This article attempts to analyse and investigate the implications of the approach to the applicability of Article XX GATT adopted in the recent China – Raw Materials. Using the decision on the non-availability of Article XX defences for violations of China’s WTO-plus commitments on export duties as a backdrop, it scrutinizes the more general, ‘systemic’ approach to the applicability of Article XX exceptions developed by theWTO dispute settlement bodies, and sheds light on the implications of such approach with respect to the relationship between GATT 1994 andWTO obligations arising from different instruments of theWTOAgreement, such as new members’ accession protocols. It also suggests that an exception to this general approach could be envisaged when the fundamental environmental goals protected under Article XX b) and g) are at stake.

Agents, Trustees, and International Courts: Nomination and Appointment of Judicial Candidates in the WTO Appellate Body

Scholars have increasingly theorized, and debated, the decision by states to create and delegate authority to international courts, as well as the subsequent autonomy and behavior of those courts, with principal–agent and trusteeship models disagreeing on the nature and extent of states’ influence on international judges. This article formulates and tests a set of principal–agent hypotheses about the ways in which, and the conditions under which, member states are able use their powers of judicial nomination and appointment to influence the endogenous preferences of international judges. The empirical analysis surveys the record of all judicial appointments to the Appellate Body (AB) of the World Trade Organization over a 15-year period. We present a view of an AB appointment process that, far from representing a pure search for expertise, is deeply politicized and offers member-state principals opportunities to influence AB members ex ante and possibly ex post. We further demonstrate that the AB nomination process has become progressively more politicized over time as member states, responding to earlier and controversial AB decisions, became far more concerned about judicial activism and more interested in the substantive opinions of AB candidates, systematically championing candidates whose views on key issues most closely approached their own, and opposing candidates perceived to be activist or biased against their substantive preferences. Although specific to the WTO, our theory and findings have implications for the judicial politics of a large variety of global and regional international courts and tribunals.

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

How common is the lipid body-containing interstitial cell in the mammalian lung?

Pulmonary lipofibroblasts are thought to be involved in lung development, regeneration, vitamin A storage, and surfactant synthesis. Most of the evidence for these important functions relies on mouse or rat studies. Therefore, the present study was designed to investigate the presence of lipofibroblasts in a variety of early postnatal and adult mammalian species (including humans) to evaluate the ability to generalize functions of this cell type for other species. For this purpose, lung samples from 14 adult mammalian species as well as from postnatal mice, rats, and humans were investigated using light and electron microscopic stereology to obtain the volume fraction and the total volume of lipid bodies. In adult animals, lipid bodies were observed only, but not in all rodents. In all other species, no lipofibroblasts were observed. In rodents, lipid body volume scaled with body mass with an exponent b = 0.73 in the power law equation. Lipid bodies were not observed in postnatal human lungs but showed a characteristic postnatal increase in mice and rats and persisted at a lower level in the adult animals. Among 14 mammalian species, lipofibroblasts were only observed in rodents. The great increase in lipid body volume during early postnatal development of the mouse lung confirms the special role of lipofibroblasts during rodent lung development. It is evident that the cellular functions of pulmonary lipofibroblasts cannot be transferred easily from rodents to other species, in particular humans.

Whole-body motion discrimination in the visually impaired

Visually impaired people show superior abilities in various perception tasks such as auditory attention, auditory temporal resolution, auditory spatial tuning, and odor discrimination. However, with the use of psychophysical methods, auditory and olfactory detection thresholds typically do not differ between visually impaired and sighted participants. Using a motion platform we investigated thresholds of passive whole-body motion discrimination in nine visually impaired participants and nine age-matched sighted controls. Participants were rotated in yaw, tilted in roll, and translated along the y-axis at two different frequencies (0.3 Hz and 2 Hz). An adaptive 3-down 1-up staircase procedure was used along with a two-alternative direction (leftward vs. rightward) discrimination task. Superior performance of visually impaired participants was found in the 0.3 Hz roll tilt condition. No differences between the visually impaired and controls were observed in all other types of motion. The superior performance in the 0.3 Hz roll tilt condition could reflect differences in the integration of extra-vestibular cues and increased sensitivity towards changes in the direction of the gravito-inertial force. In the absence of visual information, roll tilts entail a more pronounced risk of falling, and this could eventually account for the group difference. It is argued that differences in experimental procedures (i.e. detection vs. discrimination of stimuli) explain the discrepant findings across perceptual tasks comparing blind and sighted participants.

Accuracy of computed tomography angiography in the detection of pulmonary embolism in patients with high body weight

BACKGROUND The accuracy of CT pulmonary angiography (CTPA) in detecting or excluding pulmonary embolism has not yet been assessed in patients with high body weight (BW). METHODS This retrospective study involved CTPAs of 114 patients weighing 75-99 kg and those of 123 consecutive patients weighing 100-150 kg. Three independent blinded radiologists analyzed all examinations in randomized order. Readers' data on pulmonary emboli were compared with a composite reference standard, comprising clinical probability, reference CTPA result, additional imaging when performed and 90-day follow-up. Results in both BW groups and in two body mass index (BMI) groups (BMI <30 kg/m(2) and BMI ≥ 30 kg/m(2), i.e., non-obese and obese patients) were compared. RESULTS The prevalence of pulmonary embolism was not significantly different in the BW groups (P=1.0). The reference CTPA result was positive in 23 of 114 patients in the 75-99 kg group and in 25 of 123 patients in the ≥ 100 kg group, respectively (odds ratio, 0.991; 95% confidence interval, 0.501 to 1.957; P=1.0). No pulmonary embolism-related death or venous thromboembolism occurred during follow-up. The mean accuracy of three readers was 91.5% in the 75-99 kg group and 89.9% in the ≥ 100 kg group (odds ratio, 1.207; 95% confidence interval, 0.451 to 3.255; P=0.495), and 89.9% in non-obese patients and 91.2% in obese patients (odds ratio, 0.853; 95% confidence interval, 0.317 to 2.319; P=0.816). CONCLUSION The diagnostic accuracy of CTPA in patients weighing 75-99 kg or 100-150 kg proved not to be significantly different.