Late presentation of HIV-infected individuals

Late presentation remains a major concern despite the dramatically improved prognosis realized by ART. We define a first presentation for HIV care during the course of HIV infection as 'late' if an AIDS-defining opportunistic disease is apparent, or if CD4+ T-cells are <200/microl. In the Western world, approximately 10 and 30% of HIV-infected individuals still present with CD4+ T-cells <50 and <200/microl, respectively; estimates are substantially higher for developing countries. Diagnosis and treatment of opportunistic diseases and intense supportive in-hospital care take precedence over ART. Benefits of starting ART without delay, that is, when opportunistic diseases are still active, include faster resolution of opportunistic diseases and a decreased risk of recurrence. The downside of starting ART without delay could include toxicity, drug interactions and immune reconstitution inflammatory syndrome (IRIS). Among asymptomatic or oligosymptomatic individuals presenting late, where ART and primary prophylaxis are initiated, approximately 10-20% will become symptomatic from drug toxicity or undiagnosed opportunistic complications, including IRIS, which require appropriate therapies. In this review we describe late presentation to HIV care, the scale of the problem, the evaluation of a late-presenting patient and challenges associated with initiation of potent antiretroviral therapy (ART) in the setting of acute opportunistic infections and other comorbidities.

Psychometric properties of the MacNew heart disease health-related quality of life instrument in patients with heart failure

RATIONALE, AIMS AND OBJECTIVES: Heart failure (HF) is a severe chronic disease and impairs health-related quality of life (HRQL). While validated specific HRQL instruments are required for evaluation of treatment and rehabilitation in patients with HF, a single validated measure to document changes in HRQL for patients with different heart disease diagnoses would be invaluable. The purpose of this analysis was the psychometric analysis of the German MacNew Heart Disease Questionnaire (MacNew) in HF patients, which has previously been shown to be reliable and valid in patients with myocardial infarction, angina pectoris and arrhythmia. METHODS: We recruited 89 patients (61.7+/-11.5 years; 84.3% male) in two Austrian and one Swiss cardiology department with documented HF (effect sizes 28.9+/-10.1%). The self-administered MacNew, the Short Form-36 (SF-36) and the Hospital Anxiety and Depression Scale were completed. Internal consistency reliability (Cronbach's alpha), discriminative and evaluative validity were assessed. RESULTS: Cronbach's alpha exceeded 0.80. Each MacNew scale differentiated between patients with and without anxiety (3.9+/-1.0 vs. 5.3+/-0.8, all P<0.001), with and without depression (4.2+/-1.2 vs. 5.2+/-0.9 all P<0.03) and by the SF-36 health transition item (deteriorate=4.39, no change=4.95, improve=5.45, all P<0.02). Evaluative validity was demonstrated with effect sizes >0.70 for a subsample attending a 12-week outpatient rehabilitation programme. CONCLUSIONS: The German language version of the MacNew demonstrates consistently acceptable psychometric properties of reliability, validity and responsiveness in patients with documented HF. Together with previous documentation of reliability, validity and responsive, these findings strengthen the argument for the MacNew as a potential 'core' HRQL measure, at least in the German language.

The geography of large-scale land acquisitions: Analysing socio-ecological patterns of target contexts in the global South

This paper analyses local geographical contexts targeted by transnational large-scale land acquisitions (>200 ha per deal) in order to understand how emerging patterns of socio-ecological characteristics can be related to processes of large-scale foreign investment in land. Using a sample of 139 land deals georeferenced with high spatial accuracy, we first analyse their target contexts in terms of land cover, population density, accessibility, and indicators for agricultural potential. Three distinct patterns emerge from the analysis: densely populated and easily accessible croplands (35% of land deals); remote forestlands with lower population densities (34% of land deals); and moderately populated and moderately accessible shrub- or grasslands (26% of land deals). These patterns are consistent with processes described in the relevant case study literature, and they each involve distinct types of stakeholders and associated competition over land. We then repeat the often-cited analysis that postulates a link between land investments and target countries with abundant so-called “idle” or “marginal” lands as measured by yield gap and available suitable but uncultivated land; our methods differ from the earlier approach, however, in that we examine local context (10-km radius) rather than countries as a whole. The results show that earlier findings are disputable in terms of concepts, methods, and contents. Further, we reflect on methodologies for exploring linkages between socioecological patterns and land investment processes. Improving and enhancing large datasets of georeferenced land deals is an important next step; at the same time, careful choice of the spatial scale of analysis is crucial for ensuring compatibility between the spatial accuracy of land deal locations and the resolution of available geospatial data layers. Finally, we argue that new approaches and methods must be developed to empirically link socio-ecological patterns in target contexts to key determinants of land investment processes. This would help to improve the validity and the reach of our findings as an input for evidence-informed policy debates.

Ultrasound evaluation of synovitis in RA: correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r = 0.41, P < 0.0001). The same was true for the PwD score (r = 0.41, P < 0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r = 0.54, P < 0.0001 and r = 0.46, P < 0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

International validation of a behavioral scale in Parkinson's disease without dementia.

The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society.

Mechanisms of recognition and binding of α-TTP to the plasma membrane by multi-scale molecular dynamics simulations

We used multiple sets of simulations both at the atomistic and coarse-grained level of resolution to investigate interaction and binding of α-tochoperol transfer protein (α-TTP) to phosphatidylinositol phosphate lipids (PIPs). Our calculations indicate that enrichment of membranes with such lipids facilitate membrane anchoring. Atomistic models suggest that PIP can be incorporated into the binding cavity of α-TTP and therefore confirm that such protein can work as lipid exchanger between the endosome and the plasma membrane. Comparison of the atomistic models of the α-TTP-PIPs complex with membrane-bound α-TTP revealed different roles for the various basic residues composing the basic patch that is key for the protein/ligand interaction. Such residues are of critical importance as several point mutations at their position lead to severe forms of ataxia with vitamin E deficiency (AVED) phenotypes. Specifically, R221 is main residue responsible for the stabilization of the complex. R68 and R192 exchange strong interactions in the protein or in the membrane complex only, suggesting that the two residues alternate contact formation, thus facilitating lipid flipping from the membrane into the protein cavity during the lipid exchange process. Finally, R59 shows weaker interactions with PIPs anyway with a clear preference for specific phosphorylation positions, hinting a role in early membrane selectivity for the protein. Altogether, our simulations reveal significant aspects at the atomistic scale of interactions of α-TTP with the plasma membrane and with PIP, providing clarifications on the mechanism of intracellular vitamin E trafficking and helping establishing the role of key residue for the functionality of α-TTP.

Contextualizing local-scale point sample data using global-scale spatial datasets: Lessons learnt from the analysis of large-scale land acquisitions

This paper examines how the geospatial accuracy of samples and sample size influence conclusions from geospatial analyses. It does so using the example of a study investigating the global phenomenon of large-scale land acquisitions and the socio-ecological characteristics of the areas they target. First, we analysed land deal datasets of varying geospatial accuracy and varying sizes and compared the results in terms of land cover, population density, and two indicators for agricultural potential: yield gap and availability of uncultivated land that is suitable for rainfed agriculture. We found that an increase in geospatial accuracy led to a substantial and greater change in conclusions about the land cover types targeted than an increase in sample size, suggesting that using a sample of higher geospatial accuracy does more to improve results than using a larger sample. The same finding emerged for population density, yield gap, and the availability of uncultivated land suitable for rainfed agriculture. Furthermore, the statistical median proved to be more consistent than the mean when comparing the descriptive statistics for datasets of different geospatial accuracy. Second, we analysed effects of geospatial accuracy on estimations regarding the potential for advancing agricultural development in target contexts. Our results show that the target contexts of the majority of land deals in our sample whose geolocation is known with a high level of accuracy contain smaller amounts of suitable, but uncultivated land than regional- and national-scale averages suggest. Consequently, the more target contexts vary within a country, the more detailed the spatial scale of analysis has to be in order to draw meaningful conclusions about the phenomena under investigation. We therefore advise against using national-scale statistics to approximate or characterize phenomena that have a local-scale impact, particularly if key indicators vary widely within a country.