Tratamento da malária com artesunate (retocaps®) em crianças da Amazônia brasileira

Avaliamos a resposta clínica e parasitológica à terapêutica com o artesunate retocaps®, em 32 crianças internadas na Fundação de Medicina Tropical do Amazonas, que apresentavam malária com quadro clínico moderado e grave. Destas, 29 tinham a doença por P. falciparum e três, P. vivax. A melhora clínica foi observada após 24 horas do início da terapêutica, com 33,3% de pacientes afebris e, 48 horas após o tratamento, 77,2% das crianças não apresentavam febre. O acompanhamento da parasitemia assexuada, mostrou que no D2 58,6% das crianças com malária falciparum estavam negativas; em D4 todas haviam negativado, tanto na malária pelo P. falciparum como pelo P. vivax. No seguimento prolongado, na malária P. falciparum, encontramos 66,6% de recrudescências. Os resultados nos permitem concluir pela eficácia e praticidade no uso do artesunate retocaps® com rápida redução da parasitemia e melhora clínica. Entretanto, na malária P. falciparum a taxa de recrudescência foi elevada. Não foi observado para-efeito que possa ser imputado ao uso da droga.

Interlinkages and forecasting made possible by the use of the DECOIN analytical tool kit

This technical report is a document prepared as a deliverable [D4.3 Report of the Interlinkages and forecasting prototype tool] of a EU project – DECOIN Project No. 044428 - FP6-2005-SSP-5A. The text is divided into 4 sections: (1) this short introductory section explains the purpose of the report; (2) the second section provides a general discussion of a systemic problem found in existing quantitative analysis of sustainability. It addresses the epistemological implications of complexity, which entails the need of dealing with the existence of Multiple-Scales and non-equivalent narratives (multiple dimensions/attributes) to be used to define sustainability issues. There is an unavoidable tension between a “steady-state view” (= the perception of what is going on now – reflecting a PAST --& PRESENT view of the reality) versus an “evolutionary view” (= the unknown transformation that we have to expect in the process of becoming of the observed reality and in the observer – reflecting a PRESENT --& FUTURE view of the reality). The section ends by listing the implications of these points on the choice of integrated packages of sustainability indicators; (3) the third section illustrates the potentiality of the DECOIN toolkit for the study of sustainability trade-offs and linkages across indicators using quantitative examples taken from cases study of another EU project (SMILE). In particular, this section starts by addressing the existence of internal constraints to sustainability (economic versus social aspects). The narrative chosen for this discussion focuses on the dark side of ageing and immigration on the economic viability of social systems. Then the section continues by exploring external constraints to sustainability (economic development vs the environment). The narrative chosen for this discussion focuses on the dark side of current strategy of economic development based on externalization and the “bubbles-disease”; (4) the last section presents a critical appraisal of the quality of energy data found in energy statistics. It starts with a discussion of the general goal of statistical accounting. Then it introduces the concept of multipurpose grammars. The second part uses the experience made in the activities of the DECOIN project to answer the question: how useful are EUROSTAT energy statistics? The answer starts with an analysis of basic epistemological problems associated with accounting of energy. This discussion leads to the acknowledgment of an important epistemological problem: the unavoidable bifurcations in the mechanism of accounting needed to generate energy statistics. By using numerical example the text deals with the following issues: (i) the pitfalls of the actual system of accounting in energy statistics; (ii) a critical appraisal of the actual system of accounting in BP statistics; (iii) a critical appraisal of the actual system of accounting in Eurostat statistics. The section ends by proposing an innovative method to represent energy statistics which can result more useful for those willing develop sustainability indicators.

Tectonic evolution of the High Himalaya in upper Lahul (NW Himalaya, India)

The Upper Lahul region in the NW Himalaya is located in the transition zone between the High Himalayan Crystalline (HHC) to the SW and the Tethyan Zone sedimentary series to the NE. The tectonic evolution of these domains during the Himalayan Orogeny is the consequence of a succession of five deformation events. An early D1 phase corresponds to synmetamorphic, NE verging folding. This deformation created the Tandi Syncline, which consists of Permian to Jurassic Tethyan metasediments cropping out in the core of a large-scale synformal fold within the HHC paragneiss. This tectonic event is interpreted as related to a NE directed nappe stacking (Shikar Beh Nappe), probably during the late Eocene to the early Oligocene. A subsequent D2a phase caused SW verging folding in the HHC. This deformation is interpreted as contemporaneous with late Oligocene to early Miocene SW directed thrusting along the Main Central Thrust. In the Tethyan Zone, a D2b phase is marked by a decollement thrust, a system of reverse faults, and gentle folds, associated with SW directed tectonic movements. This deformation is related to an imbricate structure, characteristic of a shallow structural level, and developed in the frontal part of a nappe affecting the Tethyan Zone units of SE Zanskar (Nyimaling-Tsarap Nappe). A later D3 phase generated the Chandra Dextral Shear Zone (CDSZ), a large-scale, ductile, dextral strike-slip shear zone, located in the transition zone between the HHC and the Tethyan Himalaya. The CDSZ most likely represents a part of a system of early Miocene extensional and/or dextral, strike-slip shear zones-observed at the HHC-Tethyan Zone contact along the entire Himalaya. A final D4 phase induced large-scale doming and NE:verging back folding.

How Low Can We Go in Contrast-Enhanced CT Imaging of the Chest?: A Dose-Finding Cadaver Study Using the Model-based Iterative Image Reconstruction Approach.

RATIONALE AND OBJECTIVES: Dose reduction may compromise patients because of a decrease of image quality. Therefore, the amount of dose savings in new dose-reduction techniques needs to be thoroughly assessed. To avoid repeated studies in one patient, chest computed tomography (CT) scans with different dose levels were performed in corpses comparing model-based iterative reconstruction (MBIR) as a tool to enhance image quality with current standard full-dose imaging. MATERIALS AND METHODS: Twenty-five human cadavers were scanned (CT HD750) after contrast medium injection at different, decreasing dose levels D0-D5 and respectively reconstructed with MBIR. The data at full-dose level, D0, have been additionally reconstructed with standard adaptive statistical iterative reconstruction (ASIR), which represented the full-dose baseline reference (FDBR). Two radiologists independently compared image quality (IQ) in 3-mm multiplanar reformations for soft-tissue evaluation of D0-D5 to FDBR (-2, diagnostically inferior; -1, inferior; 0, equal; +1, superior; and +2, diagnostically superior). For statistical analysis, the intraclass correlation coefficient (ICC) and the Wilcoxon test were used. RESULTS: Mean CT dose index values (mGy) were as follows: D0/FDBR = 10.1 ± 1.7, D1 = 6.2 ± 2.8, D2 = 5.7 ± 2.7, D3 = 3.5 ± 1.9, D4 = 1.8 ± 1.0, and D5 = 0.9 ± 0.5. Mean IQ ratings were as follows: D0 = +1.8 ± 0.2, D1 = +1.5 ± 0.3, D2 = +1.1 ± 0.3, D3 = +0.7 ± 0.5, D4 = +0.1 ± 0.5, and D5 = -1.2 ± 0.5. All values demonstrated a significant difference to baseline (P < .05), except mean IQ for D4 (P = .61). ICC was 0.91. CONCLUSIONS: Compared to ASIR, MBIR allowed for a significant dose reduction of 82% without impairment of IQ. This resulted in a calculated mean effective dose below 1 mSv.

Quantification of nicotine, cotinine, trans-3'-hydroxycotinine and varenicline in human plasma by a sensitive and specific UPLC-tandem mass-spectrometry procedure for a clinical study on smoking cessation.

A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100mm, 1.7μm). A gradient program was used, with a 10mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500ng/mL for nicotine, 1-1000ng/mL for cotinine, 2-1000ng/mL for trans-3'-hydroxycotinine and 1-500ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.

Genetic polymorphisms in folate pathway enzymes, DRD4 and GSTM1 are related to temporomandibular disorder

BACKGROUND Temporomandibular disorder (TMD) is a multifactorial syndrome related to a critical period of human life. TMD has been associated with psychological dysfunctions, oxidative state and sexual dimorphism with coincidental occurrence along the pubertal development. In this work we study the association between TMD and genetic polymorphisms of folate metabolism, neurotransmission, oxidative and hormonal metabolism. Folate metabolism, which depends on genes variations and diet, is directly involved in genetic and epigenetic variations that can influence the changes of last growing period of development in human and the appearance of the TMD. METHODS A case-control study was designed to evaluate the impact of genetic polymorphisms above described on TMD. A total of 229 individuals (69% women) were included at the study; 86 were patients with TMD and 143 were healthy control subjects. Subjects underwent to a clinical examination following the guidelines by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Genotyping of 20 Single Nucleotide Polymorphisms (SNPs), divided in two groups, was performed by multiplex minisequencing preceded by multiplex PCR. Other seven genetic polymorphisms different from SNPs (deletions, insertions, tandem repeat, null genotype) were achieved by a multiplex-PCR. A chi-square test was performed to determine the differences in genotype and allelic frequencies between TMD patients and healthy subjects. To estimate TMD risk, in those polymorphisms that shown significant differences, odds ratio (OR) with a 95% of confidence interval were calculated. RESULTS Six of the polymorphisms showed statistical associations with TMD. Four of them are related to enzymes of folates metabolism: Allele G of Serine Hydoxymethyltransferase 1 (SHMT1) rs1979277 (OR = 3.99; 95%CI 1.72, 9.25; p = 0.002), allele G of SHMT1 rs638416 (OR = 2.80; 95%CI 1.51, 5.21; p = 0.013), allele T of Methylentetrahydrofolate Dehydrogenase (MTHFD) rs2236225 (OR = 3.09; 95%CI 1.27, 7.50; p = 0.016) and allele A of Methionine Synthase Reductase (MTRR) rs1801394 (OR = 2.35; 95CI 1.10, 5.00; p = 0.037). An inflammatory oxidative stress enzyme, Gluthatione S-Tranferase Mu-1(GSTM1), null allele (OR = 2.21; 95%CI 1.24, 4.36; p = 0.030) and a neurotransmission receptor, Dopamine Receptor D4 (DRD4), long allele of 48 bp-repeat (OR = 3.62; 95%CI 0.76, 17.26; p = 0.161). CONCLUSIONS Some genetic polymorphisms related to folates metabolism, inflammatory oxidative stress, and neurotransmission responses to pain, has been significantly associated to TMD syndrome.

Measles outbreak in Andalusia, Spain, January to August 2011.

On 7 January 2011, a six year-old child living in a Roma community near Seville, southern Spain, was hospitalised with measles. Contact tracing identified a probable index case with onset of symptoms on 20 December 2011 and several unreported cases among children under the age of 15 years in the same town. The outbreak initially spread in districts in the city of Seville with a high proportion of Roma residents, and later to other cities and towns in Andalusia. While some towns experienced wide spread of the disease with significant clusters of cases, most of the affected locations saw non-clustered cases or very few secondary cases. The outbreak resulted in 1,759 confirmed or probable cases of which 393 (19%) required hospitalisation. Measles virus of genotype D4 was diagnosed in more than half of the cases. Significant differences (p<0.0001) by age group were found between clustered and non-clustered cases. The highest proportion of clustered cases occurred in the age group of 5-14 yearolds, while the highest proportion of non-clustered cases was seen in those older than 29 years. The last confirmed case related to this outbreak was reported on 20 August 2011.

Calculation of Franck-Condon factors including anharmonicity: simulation of the C2 H4+ X̃2B 3u←C2 H4X̃1 Ag band in the photoelectron spectrum of ethylene

Our new simple method for calculating accurate Franck-Condon factors including nondiagonal (i.e., mode-mode) anharmonic coupling is used to simulate the C2H4+X2B 3u←C2H4X̃1 Ag band in the photoelectron spectrum. An improved vibrational basis set truncation algorithm, which permits very efficient computations, is employed. Because the torsional mode is highly anharmonic it is separated from the other modes and treated exactly. All other modes are treated through the second-order perturbation theory. The perturbation-theory corrections are significant and lead to a good agreement with experiment, although the separability assumption for torsion causes the C2 D4 results to be not as good as those for C2 H4. A variational formulation to overcome this circumstance, and deal with large anharmonicities in general, is suggested

Desenvolvimento pós-embrionário de Pattonella intermutans (Thomson) (Diptera: Sarcophagidae) em diferentes dietas

A proposta deste estudo foi de avaliar o desenvolvimento pós-embrionário de Pattonella intermutans (Thomson, 1869) em dietas artificiais preparadas com agar-agar. Dieta D1: leite em pó integral + fermento biológico; Dieta D2: leite em pó integral + fermento biológico + caseína; Dieta D3: leite em pó integral + ovo cru; Dieta D4: carne bovina moída (dieta controle). A carne bovina moída foi a dieta mais eficiente (peso larval de 195,63 mg e viabilidade de neolarva a adulto de 86,5%), quando comparada com as dietas artificiais. Os seguintes resultados foram obtidos para o grupo experimental: Dieta D3: 180,15 mg e 63,5%; Dieta D2: 141,07 mg e 61% e na Dieta D1: 147,98 mg e 51,5%.

Single Subject Finger Somatotopy Mapping at 7T.

Introduction: The primary somatosensory cortex (SI) contains Brodmann areas (BA) 1, 2, 3a, and 3b. Research in non-human primates showed that BAs 3b, 1, and 2 each contain one full representation of the hand with separate representations for each finger. This research also showed that the finger representation in BA3b has larger and clearer finger somatotopy than BA1 and 2. Although several efforts to map finger somatotopy in SI by fMRI have been made at 1.5 and 3T these studies have yielded variable results and were not able to detect single subject finger somatotopy, probably due to the limited spatial extent of the cortical areas representing a digit (close to the resolution in most fMRI experiments), complications due to acquisition of consistent maps for individual subjects (Schweizer et al 2008), or inter-individual variability in sulcal anatomy impeding group studies. Here, we used 7T fMRI to investigate finger somatotopy in SI, some of its functional characteristics, and its reproducibility. Methods: Eight right-handed male subjects were scanned on a 7T scanner (Siemens Medical, Germany) with an 8-channel Tx/Rx rf-coil (Rapid Biomedical, Germany). 1.3x1.3x1.3mm3 resolution fMRI data were acquired using a sinusoidal readout EPI sequence (Speck et al, 2008) and FOV=210mm, TE/TR=27ms/2.5s, GRAPPA=2. Each volume contained 28 transverse slices covering SI. A single EPI volume with 64 slices was acquired to aid coregistration. 1x1x1mm3 anatomical data were acquire using the MP2RAGE sequence (Marques et al, 2009; TE/TR/TI1,2/TRmprage=2.63ms/7.2ms/0.9,3.2s/5s). Subjects were positioned supine in the scanner with their right arm comfortably against the magnet bore. An experimenter was positioned at the entrance of the bore where he could easily reach and stroke successively the two distal phalanxes of each digit. The order of stroked digit was D1 (thumb)-D3-D5-D2-D4, with 20s ON, 10s OFF alternated. This sequence was repeated four times per run and two functional runs were acquired per subject. Realignment, smoothing (FWHM 2 mm), coregistration of the anatomical to the fMRI data and calculation of t-statistics were done using SPM8. An SI mask was obtained via an F-contrast (p<0.001) over all digits. Within the mask, voxels were labeled with the number of the digit demonstrating the highest t-value for that particular voxel. Results: For all subjects, areas corresponding to the five digits were identified in contralateral SI. BA3b showed the most consistent somatotopic finger representation (see an example in Fig.1). The five digits were localized in a consecutive order in the cortex, with D1 most anterior, inferior and distal and D5, most posterior, superior and medial (mean distance between centres of mass of digit representations ±stderr: 4.2±0.7mm; see Fig. 2). The analysis of average beta values within each finger representation region revealed the specificity of the somatotopic region to the tactile input for each tested finger (except digit 4 and 5). Five of these subjects also presented an orderly and consecutive representation of the five digits in BA1 and 2. Conclusions: Our data reveal that the increased BOLD sensitivity at 7T and the high spatial resolution used in this study allow consistent somatotopic mapping using human touch as a stimulus and that human SI contains at least three separate regions that contain five separate representations of all single contralateral fingers. Moreover, adjacent fingers were represented at adjacent cortical regions across the three SI regions. The spatial organization of SI as reflected in individual subject topography corresponds well with previous electrophysiological data in non-human primates. The small distance between digit representations highlights the need for the high spatial resolution available at 7T.

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Estudio tafonómico del yacimiento de Ventalló (Gerona)

En el presente trabajo se estudian aspectos tafonmicos -tanto biostratinmicos como fosildiagenticos- del yacimiento Pliocnico de Ventall (Gerona, Espaa). Se llega a la conclusin 'de que existe una preservacin diferencial de los Foraminferos y Pectnidos frente a las Moluscos en general debido a diferencias microestructurales ; la Tafocenosis se form en m m& sedimentario prximo a la costa y d4- bilmente oxidante.

Comment améliorer la reproductibilité de lecture des VFA en dépistage clinique? la cohorte OsteoLaus.

Introduction. - Les fractures ostéoporotiques entrainent une morbi-mortalité et des coûts économiques et humains grandissants. Des campagnes de dépistage se mettent en place associant questionnaire et DXA afin d'évaluer le risque fracturaire individuel et populationnel. La découverte fortuite d'une fracture vertébrale (VF), rendue possible par la réalisation d'une morphométrie vertébrale de profil (VFA par DXA) de D4 à L4, peut changer le diagnostic et le pronostic. Néanmoins sa reproductibilité de lecture est peu élevée, surtout sur le rachis dorsal et les fractures de grade 1 [1]. L'IOF/ISCD a proposé un guide pour en améliorer la lecture. Nous avons mesuré la reproductibilité de lecture des VFA avant et après application de ce guide sur une cohorte Suisse de dépistage de l'ostéoporose. Patients et méthodes. - 360 VFA (Hologic Delphi) issus aléatoirement de la cohorte OstéoLaus (femmes > 50 ans) ont été lus par 2 lecteurs indépendants avant et après application du guide de lecture. Il comporte des règles de condition de lecture (luminosité, contraste sur l'écran) et des étapes de lecture systématisées. La reproductibilité a été évaluée par le test de kappa sur : la lisibilité de chaque vertèbre, l'existence ou non d'une VF, son grade (1, 2 ou 3 selon Genant). Nous avons utilisé le Kappa de Cohen avec une technique de bootstrap pour les comparaisons avant/après sur des données corrélées. Résultats. - L'accord entre les lecteurs est élevé et s'améliore après application du guide de lecture (tableau). Le kappa de Cohen est modéré à bon selon Landis et Koch (0,4-0,7). La reproductibilité sur les grades est améliorée en regroupant les grades 0/1 et 2/3, mais pas par le guide de lecture. Conclusion. - L'utilisation du guide de lecture des VFA IOF/ISCD améliore la reproductibilité sur la lisibilité des vertèbres, la détection des VF, mais pas la classification du grade selon Genant. Ceci est principalement expliqué par le fait que le kappa de Cohen donne beaucoup d'importance à la distribution des données, qui devient asymétrique lorsque l'événement est rare. Le kappa uniforme [2] serait mieux adapté dans cette situation. Une réanalyse est en cours.