Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data

Abstract: Purpose Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments. Patients and Methods A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test. Results Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard rati...

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

Abstract: Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

Historical review of malarial control in southern African with emphasis on the use of indoor residual house-spraying

Abstract: Indoor residual house-spraying (IRS) mainly with dichlorodiphenyltrichloroethane (DDT) was the principal method by which malaria was eradicated or greatly reduced in many countries in the world between the 1940s and 1960s. In sub-Saharan Africa early malarial eradication pilot projects also showed that malaria is highly responsive to vector control by IRS but transmission could not be interrupted in the endemic tropical and lowland areas. As a result IRS was not taken to scale in most endemic areas of the continent with the exception of southern Africa and some island countries such as Reunion, Mayotte, Zanzibar, Cape Verde and Sao Tome. In southern Africa large-scale malarial control operations based on IRS with DDT and benzene hexachloride (BHC) were initiated in a number of countries to varying degrees. The objective of this review was to investigate the malarial situation before and after the introduction of indoor residual insecticide spraying in South Africa, Swaziland, Botswana, Namibia, Zimbabwe and Mozambique using historical malarial data and related information collected from National Malaria Control Programmes, national archives and libraries, as well as academic institutions in the respective countries. Immediately after the inception of IRS with insecticides, dramatic reductions in malaria and its vectors were recorded. Countries that developed National Malaria Control Programmes during this phase and had built up human and organizational resources made significant advances towards malarial control. Malaria was reduced from hyper- to meso-endemicity and from meso- to hypo-endemicity and in certain instances to complete eradication. Data are presented on the effectiveness of IRS as a malarial control tool in six southern African countries. Recent trends in and challenges to malarial control in the region are also discussed.

Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance

Abstract: Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion.