Pritnary care in South Africa Reflections on conceptualisation and a review of the recent literature

This paper reviews the various interpretations and connotations of the term 'primary care' as employed in South African literature and practice. There is a need for clear definitions of key concepts and the utility of the primary care framework proposed by Barbara Starfield is suggested in this regard. The paper also reviews and evaluates the research on primary care in South Africa published since 1988

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Gold nanoparticles show electroactivity: counting and sorting nanoparticles upon impact with electrodes.

Gold nanoparticles (AuNPs) in aqueous 0.10 M HCl are shown to be electroactive at oxidising potentials greater than 1.0 V (vs. Ag/AgCl) by means of voltammetric monitoring of AuNP-electrode collisions. The method promises the use of anodic particle coulometry for the detection and characterisation of the AuNPs

Influences and hegemonies in health reform research

Analizamos la evolución de las publicaciones, incluidas en MEDLINE, LILACS y Sociological Abstracts, sobre las Reformas de Salud en el mundo y las influencias que determinan su orientación y distribución en el período de 1990-2004. En total se seleccionaron 8.729 publicaciones. Los principios de “Sostenibilidad” y “Calidad y Efectividad” son los más atendidos, existiendo distintos patrones de atención, dependiendo de regiones y países. De 199 países, el 61% tiene referencia sobre sus procesos de reforma, siendo Estados Unidos y Gran Bretaña los que agrupan la mayor cantidad. Se observó que existen fuertes influencias para el estudio de las Reformas de Salud, provenientes de los patrones Británico y Norteamericano de atención a los Principios de Reforma. Esto puede estar limitando la visibilidad científica de cuestiones como la equidad, participación y eficiencia.The authors analyze the evolution in publications indexed in MEDLINE, LILACS, and Sociological Abstracts concerning health reforms around the world and the determinants of their orientation and distribution from 1990 to 2004. A total of 8,729 publications were selected. The principles of “sustainability” and “quality and effectiveness” were dealt with most frequently, with different patterns of attention, depending on the regions and countries. Of 199 countries, 61% included references as to their health reform processes, with the largest numbers in the United States and the Great Britain. The British and U.S. standards for attention to health reform principles displayed strong influences on the study of health reforms elsewhere. This may limit the scientific visibility of issues like equity, participation, and efficiency

The emerging role of viral vectors as vehicles for DMD gene editing

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin-encoding DMD gene. The DMD gene, spanning over 2.4 megabases along the short arm of the X chromosome (Xp21.2), is the largest genetic locus known in the human genome. The size of DMD, combined with the complexity of the DMD phenotype and the extent of the affected tissues, begs for the development of novel, ideally complementary, therapeutic approaches. Genome editing based on the delivery of sequence-specific programmable nucleases into dystrophin-defective cells has recently enriched the portfolio of potential therapies under investigation. Experiments involving different programmable nuclease platforms and target cell types have established that the application of genome-editing principles to the targeted manipulation of defective DMD loci can result in the rescue of dystrophin protein synthesis in gene-edited cells. Looking towards translation into the clinic, these proof-of-principle experiments have been swiftly followed by the conversion of well-established viral vector systems into delivery agents for DMD editing. These gene-editing tools consist of zinc-finger nucleases (ZFNs), engineered homing endoculeases (HEs), transcription activator-like effector nucleases (TALENs), and RNA-guided nucleases (RGNs) based on clustered, regularly interspaced, short palindromic repeats (CRISPR)–Cas9 systems. Here, we succinctly review these fast-paced developments and technologies, highlighting their relative merits and potential bottlenecks, when used as part of in vivo and ex vivo gene-editing strategies