Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence

Background: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum. Results: Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, interpopulation differentiation, and the degree to which allele frequencies are correlated between populations. Conclusions: The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.

Application of a wrist dosimeter prototype for radiation monitoring ((153)Sm) during a therapeutic procedure simulation

Gamma and beta radiation emitting radiopharmaceuticals are handled in nuclear medicine services, and in many cases there is only individual monitoring of gamma radiation. In this paper, the results obtained using a wrist dosimeter prototype (CaSO(4):Dy + Teflon pellets) show that the doses for workers occupationally exposed to beta radiation from (153)Sm are not negligible. It is important that this dose is evaluated, and it has to be taken into consideration in the individual monitoring system.

Solubility of red 153 and blue 1 in supercritical carbon dioxide

Solubilities of red 153, (3-[[4-[[5,6(or 6,7)-dichloro-2-benzothiazolyl]azo]phenyl]ethylamino]propanenitrile), an azo compound, and disperse blue1 (1,4,5,8-tetraaminoantraquinone) in supercritical carbon dioxide (SC CO(2)) were measured at T = (333.2 to 393.2) K over the pressure range (12.0 to 40.0) MPa by a flow type apparatus. The solubility of red 153 (0.985. 10(-6) to 37.2. 10(-6)) in the overall region of measurements is found to be significantly higher than that of disperse blue 1 (1.12.10(-7) to 4.89.10(-7)). The solubility behavior of disperse red 153 follows the general solubility trend displayed by disperse dyes with a crossover pressure at about 20 MPa. On the other hand, blue 1, which is a disperse anthraquinone dye, exhibits unexpected behavior not recorded previously there is no crossover pressure at the temperature and pressure ranges studied, and the dye's solubility at T = 333.2 K practically does not increase with pressure. To the best of our knowledge, there are no previous measurements of blue 1 solubility in SC CO(2) reported in the literature. The experimental data were correlated by using the Soave Redlich Kwong equation of state (EoS) with the one-fluid van der Waals mixing rule, and an acceptable correlation of the solubility data for both dyes was obtained.

Análise Custo-Efectividade do Samário-153-EDTMP Versus Terapêutica Convencional da Dor em Doentes com Metástases Ósseas Múltiplas Dolorosas em Portugal

Introdução: O cancro da próstata é uma importante causa de morbilidade e mortalidade. Em Portugal, de acordo com um estudo publicado em 2003, a taxa de novos casos de cancro na próstata era de 53 por 100.000 homens, em 2000, com uma taxa de mortalidade padronizada pela idade de 28 por 100.000 (em 1995). As metástases ósseas múltiplas são uma das principais complicações associadas ao cancro de próstata avançado. O Samário-EDTMP mostrou ser uma alternativa segura e eficaz no tratamento paliativo da dor associada a metástases ósseas. O objectivo deste estudo económico é avaliar o custo-efectividade do tratamento da dor associada a metástases ósseas múltiplas com Samário-153-EDTMP versus terapêutica convencional da dor, no carcinoma da próstata hormono-refractário, em Portugal. Metodologia: Estudo de custo-efectividade que compara os custos directos do tratamento de doentes com múltiplas metástases ósseas dolorosas com Samário-153-EDTMP versus terapêutica convencional para a dor, na perspectiva do Sistema Nacional de Saúde, em Portugal, num horizonte temporal de quatro meses. Resultados: Os custos directos totais num período de quatro meses são 2.311,91 € para um doente tratado com Samário-153-EDTMP versus 2.450,74 € para um doente sob tratamento padrão. De acordo com o modelo, um doente tratado com Samário-153-EDTMP representa um decréscimo de custos de 138,83 €. Conclusão: O Samário-153-EDTMP é não só um método terapêutico muito eficaz mas também uma solução com custos reduzidos quando comparado à terapêutica convencional da dor, em doentes com dor devida a metástases ósseas múltiplas, em Portugal.

Recensões

Revista do IHA, N.1 (2005), pp. 143-156

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

PURPOSE: The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS: Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS: Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 ± 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS: Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.

Radiolesão vascular como efeito deletério da braquiterapia intra-arterial com dose elevada de Samário-153 em coelhos hipercolesterolêmicos

OBJETIVO: Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com Samário-153 (153 Sm) em coelhos hipercolesterolêmicos, com doses elevadas. MÉTODOS: Foram analisados 43 coelhos hipercolesterolêmicos, brancos, da raça New Zealand, e o total de 86 artérias ilíacas submetidas a lesão por balão de angioplastia. Divididos em três grupos: dois (GI) irradiados com as doses de 15Gy (n=14) e 60Gy (n=36) e um grupo controle (n=36). Foram realizadas avaliação histológica morfométrica e análise histológica qualitativa para análise tecidual. RESULTADOS: Foram observadas uma redução significativa da neoproliferação intimal (NPI) no GI 15 Gy (p<0,0001), uma redução da área de camada média (ACM) (p<0,0001) e % estenose (p<0,0001) comparada com os demais grupos. O GI 60 Gy teve o maior índice de PNI, aumento da ACM, AV e porcentagem de estenose. No GI 60 Gy, observou-se maior número de células xantomatosas (GI 60Gy:86,11% e GI 15Gy:14,29%, p<0,0001), tecido amorfo hialino (GI 60Gy:58,33% e GI 15 Gy:0%, p=0,0001) e proliferação vascular (GI60 Gy:30,56% e GI15 Gy:0%, p=0,0221). Outras análises teciduais não apresentaram diferença estatística entre os grupos. CONCLUSÃO: A dose elevada de 60Gy ocasionou intensa proliferação celular considerada radiolesão vascular, ao contrário da dose de 15Gy que apresentou excelente inibição da neo-proliferação intimal.

Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients.

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluation.

Review of the Nurse Consultant Role Northern Ireland 2005 (PDF 152 KB)

Review of the Nurse Consultant Role Northern Ireland 2005

Penalties for Patient Charge Evasion (PDF 153 KB)

Penalties for Patient Charge Evasion