Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared

BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

UPLC-ESI-TOFMS-based metabolomics and gene expression dynamics inspector self-organizing metabolomic maps as tools for understanding the cellular response to ionizing radiation

Global transcriptomic and proteomic profiling platforms have yielded important insights into the complex response to ionizing radiation (IR). Nonetheless, little is known about the ways in which small cellular metabolite concentrations change in response to IR. Here, a metabolomics approach using ultraperformance liquid chromatography coupled with electrospray time-of-flight mass spectrometry was used to profile, over time, the hydrophilic metabolome of TK6 cells exposed to IR doses ranging from 0.5 to 8.0 Gy. Multivariate data analysis of the positive ions revealed dose- and time-dependent clustering of the irradiated cells and identified certain constituents of the water-soluble metabolome as being significantly depleted as early as 1 h after IR. Tandem mass spectrometry was used to confirm metabolite identity. Many of the depleted metabolites are associated with oxidative stress and DNA repair pathways. Included are reduced glutathione, adenosine monophosphate, nicotinamide adenine dinucleotide, and spermine. Similar measurements were performed with a transformed fibroblast cell line, BJ, and it was found that a subset of the identified TK6 metabolites were effective in IR dose discrimination. The GEDI (Gene Expression Dynamics Inspector) algorithm, which is based on self-organizing maps, was used to visualize dynamic global changes in the TK6 metabolome that resulted from IR. It revealed dose-dependent clustering of ions sharing the same trends in concentration change across radiation doses. "Radiation metabolomics," the application of metabolomic analysis to the field of radiobiology, promises to increase our understanding of cellular responses to stressors such as radiation.

Isopach Maps and Discussion of the Ordovician and Devonian of Montana and Adjacent Areas

The intensive postwar search for new petroleum horizons has resulted in widespread prospecting in the northern Great Plains. No commercial production has as yet been derived from Ordovician or Devonian rocks in Montana, but the relat­ively few tests that have penetrated to critical depths have disclosed encouraging conditions which merit further consider­ation, especially in Devonian strata.

Scalp field maps and their characterization

The present chapter gives a comprehensive introduction into the display and quantitative characterization of scalp field data. After introducing the construction of scalp field maps, different interpolation methods, the effect of the recording reference and the computation of spatial derivatives are discussed. The arguments raised in this first part have important implications for resolving a potential ambiguity in the interpretation of differences of scalp field data. In the second part of the chapter different approaches for comparing scalp field data are described. All of these comparisons can be interpreted in terms of differences of intracerebral sources either in strength, or in location and orientation in a nonambiguous way. In the present chapter we only refer to scalp field potentials, but mapping also can be used to display other features, such as power or statistical values. However, the rules for comparing and interpreting scalp field potentials might not apply to such data. Generic form of scalp field data Electroencephalogram (EEG) and event-related potential (ERP) recordings consist of one value for each sample in time and for each electrode. The recorded EEG and ERP data thus represent a two-dimensional array, with one dimension corresponding to the variable “time” and the other dimension corresponding to the variable “space” or electrode. Table 2.1 shows ERP measurements over a brief time period. The ERP data (averaged over a group of healthy subjects) were recorded with 19 electrodes during a visual paradigm. The parietal midline Pz electrode has been used as the reference electrode.

Consistent Layout for Thematic Software Maps

Software visualizations can provide a concise overview of a complex software system. Unfortunately, since software has no physical shape, there is no “natural“ mapping of software to a two-dimensional space. As a consequence most visualizations tend to use a layout in which position and distance have no meaning, and consequently layout typical diverges from one visualization to another. We propose a consistent layout for software maps in which the position of a software artifact reflects its \emph{vocabulary}, and distance corresponds to similarity of vocabulary. We use Latent Semantic Indexing (LSI) to map software artifacts to a vector space, and then use Multidimensional Scaling (MDS) to map this vector space down to two dimensions. The resulting consistent layout allows us to develop a variety of thematic software maps that express very different aspects of software while making it easy to compare them. The approach is especially suitable for comparing views of evolving software, since the vocabulary of software artifacts tends to be stable over time.

Understanding Neural Maps with Topographica

The biological function of neurons can often be understood only in the context of large, highly interconnected networks. These networks typically form two-dimensional topographic maps, such as the retinotopic maps in mammalian visual cortex. Computational simulations of these areas have led to valuable insights about how cortical topography develops and functions, but further progress has been hindered due to the lack of appropriate simulation tools. This paper introduces the freely available Topographica maplevel simulator, originally developed at the University of Texas at Austin and now maintained at the University of Edinburgh, UK. Topographica is designed to make large-scale, detailed models practical. The goal is to allow neuroscientists and computational scientists to work together to understand how topographic maps and their connections organize and operate. This understanding will be crucial for integrating experimental observations into a comprehensive theory of brain function.

Book Review of “Human Behaviour and the Social Environment: Models, Metaphors, and Maps for Applying Theoretical Perspectives to Practice”. 640 pages, Thomson Brooks/Cole, 2007, by James A. Forte

This voluminous book which draws on almost 1000 references provides an important theoretical base for practice. After an informative introduction about models, maps and metaphors, Forte provides an impressive presentation of several perspectives for use in practice; applied ecological theory, applied system theory, applied biology, applied cognitive science, applied psychodynamic theory, applied behaviourism, applied symbolic interactionism, applied social role theory, applied economic theory, and applied critical theory. Finally he completes his book with a chapter on “Multi theory practice and routes to integration.”

The bovine dilated cardiomyopathy locus maps to a 1.0-Mb interval on chromosome 18

Cardiomyopathies are myocardial diseases that lead to cardiac dysfunction, heart failure, arrhythmia, and sudden death. In human medicine, cardiomyopathies frequently warrant heart transplantation in children and adults. Bovine dilated cardiomyopathy (BDCMP) is a heart muscle disorder that has been observed during the last 30 years in cattle of Holstein-Friesian origin. In Switzerland BDCMP affects Swiss Fleckvieh and Red Holstein breeds. BDCMP is characterized by a cardiac enlargement with ventricular remodeling and chamber dilatation. The common symptoms in affected animals are subacute subcutaneous edema, congestion of the jugular veins, and tachycardia with gallop rhythm. A cardiomegaly with dilatation and hypertrophy of all heart chambers, myocardial degeneration, and fibrosis are typical postmortem findings. It was shown that all BDCMP cases reported worldwide traced back to a red factor-carrying Holstein-Friesian bull, ABC Reflection Sovereign. An autosomal recessive mode of inheritance was proposed for BDCMP. Recently, the disease locus was mapped to a 6.7-Mb interval MSBDCMP06-BMS2785 on bovine Chr 18 (BTA18). In the present study the BDCMP locus was fine mapped by using a combined strategy of homozygosity mapping and association study. A BAC contig of 2.9 Mb encompassing the crucial interval was constructed to establish the correct marker order on BTA18. We show that the disease locus is located in a gene-rich interval of 1.0 Mb and is flanked by the microsatellite markers DIK3006 and MSBDCMP51.

Arachnomelia in Brown Swiss cattle maps to chromosome 5

Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited congenital disorder of the skeletal system giving affected calves a spidery look (OMIA ID 000059). Over a period of 20 years 15 cases were sampled in the Swiss and Italian Brown cattle population. Pedigree data revealed that all affected individuals trace back to a single acknowledged carrier founder sire. A genome scan using 240 microsatellites spanning the 29 bovine autosomes showed homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all cases. Linkage analysis confirmed the localization of the arachnomelia mutation in the region of the marker ETH10. Fine-mapping and haplotype analysis using a total of 34 markers in this region refined the critical region of the arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The disease-associated IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted selection. As the corresponding human and mouse chromosome segments do not contain any clear functional candidate genes for this disorder, the mutation causing arachnomelia in the Brown Swiss cattle might help to identify an unknown gene in bone development.

Microstates in language-related brain potential maps show noun-verb differences

Brain processing of grammatical word class was studied analyzing event-related potential (ERP) brain fields. Normal subjects observed a randomized sequence of single German nouns and verbs on a computer screen, while 20-channel ERP field map series were recorded separately for both word classes. Spatial microstate analysis was applied, based on the observation that series of ERP maps consist of epochs of quasi-stable map landscapes and based on the rationale that different map landscapes must have been generated by different neural generators and thus suggest different brain functions. Space-oriented segmentation of the mean map series identified nine successive, different functional microstates, i.e., steps of brain information processing characterized by quasi-stable map landscapes. In the microstate from 116 to 172 msec, noun-related maps differed significantly from verb-related maps along the left–right axis. The results indicate that different neural populations represent different grammatical word classes in language processing, in agreement with clinical observations. This word class differentiation as revealed by the spatial–temporal organization of neural activity occurred at a time after word input compatible with speed of reading.