Prioritizing genetic testing in patients with kallmann syndrome using clinical phenotypes.

Context: The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. Objective: The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Subjects: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Main Outcome Measures: Reproductive and nonreproductive phenotypes within each genetic group were measured. Results: Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicular volumes (TVs) at presentation of 1.5 ± 0.1 mL vs 3.7 ± 0.3 mL, P < .05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P < .05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P < .05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P < .05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Conclusions: Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dental agenesis (FGF8/FGFR1), digital bony abnormalities (FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening.

Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing dental caries in children.

BACKGROUND: Dietary fluoride supplements were first introduced to provide systemic fluoride in areas where water fluoridation is not available. Since 1990, the use of fluoride supplements in caries prevention has been re-evaluated in several countries. OBJECTIVES: To evaluate the efficacy of fluoride supplements for preventing dental caries in children. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 12 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12 October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October 2011), and Current Controlled Trials (to 12 October 2011). We handsearched reference lists of articles and contacted selected authors. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing, with minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges) with no fluoride supplement or with other preventive measures such as topical fluorides in children less than 16 years of age at the start. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (DMFS). DATA COLLECTION AND ANALYSIS: Two review authors, independently and in duplicate, assessed the eligibility of studies for inclusion, and carried out risk of bias assessment and data extraction. In the event of disagreement, we sought consensus and consulted a third review author. We contacted trial authors for missing information. We used the prevented fraction (PF) as a metric for evaluating the efficacy of the intervention. The PF is defined as the mean caries increment in controls minus mean caries increment in the treated group divided by mean caries increment in controls. We conducted random-effects meta-analyses when data could be pooled. We assessed heterogeneity in the results of the studies by examining forest plots and by using formal tests for homogeneity. We recorded adverse effects (fluorosis) when the studies provided relevant data. MAIN RESULTS: We included 11 studies in the review involving 7196 children.In permanent teeth, when fluoride supplements were compared with no fluoride supplement (three studies), the use of fluoride supplements was associated with a 24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on deciduous or primary teeth. In one study, no caries-inhibiting effect was observed on deciduous teeth while in another study, the use of fluoride supplements was associated with a substantial reduction in caries increment.When fluoride supplements were compared with topical fluorides or with other preventive measures, there was no differential effect on permanent or deciduous teeth.The review found limited information on the adverse effects associated with the use of fluoride supplements. AUTHORS' CONCLUSIONS: This review suggests that the use of fluoride supplements is associated with a reduction in caries increment when compared with no fluoride supplement in permanent teeth. The effect of fluoride supplements was unclear on deciduous teeth. When compared with the administration of topical fluorides, no differential effect was observed. We rated 10 trials as being at unclear risk of bias and one at high risk of bias, and therefore the trials provide weak evidence about the efficacy of fluoride supplements.

Método do hipercubo latino condicionado para a amostragem de solos na presença de covariáveis ambientais visando o mapeamento digital de solos

A amostragem é uma das etapas mais importantes dos levantamentos de solos. No entanto, os esquemas de amostragem utilizados nos levantamentos convencionais têm se evidenciado inadequados para o mapeamento digital de solos, pois podem comprometer os resultados e, além disso, não possibilitam a realização de análises estatísticas. Este estudo teve por objetivo avaliar o método de amostragem do hipercubo latino condicionado (cLHS, sigla em inglês), na presença de covariáveis ambientais (elevação, declividade, curvatura e mapa de uso e cobertura do solo), em comparação com a amostragem aleatória, na alocação de 100 pontos amostrais, buscando maior representatividade das características ambientais da bacia do rio Guapi-Macacu. O desempenho dos métodos foi avaliado pela análise qualitativa dos histogramas de frequência e das análises estatísticas pelos testes F, T de Student e Kolmogorov-Smirnov (K-S), para cada covariável. Os resultados apresentaram que os pontos selecionados pelo método cLHS possuíam distribuição geográfica mais adequada do que aqueles obtidos pela amostragem aleatória. Além disso, o método cLHS preservou mais a distribuição de frequência das covariáveis contínuas do que a amostragem aleatória; para covariável categórica uso e cobertura do solo os métodos foram equivalentes. Os testes estatísticos confirmaram o melhor desempenho do método cLHS, cujas amostras não diferiram estatisticamente da bacia. Entretanto, a amostragem aleatória apresentou diferença estatística para com a bacia, para todas as covariáveis contínuas para pelo menos um dos testes utilizados. Assim, o método cLHS pode ser considerado como um método satisfatório para seleção de locais de amostragem em áreas heterogêneas similares as deste estudo, visando a utilização no mapeamento digital de solos.

Evaluation of statistical and geostatistical models of digital soil properties mapping in tropical mountain regions

Soil properties have an enormous impact on economic and environmental aspects of agricultural production. Quantitative relationships between soil properties and the factors that influence their variability are the basis of digital soil mapping. The predictive models of soil properties evaluated in this work are statistical (multiple linear regression-MLR) and geostatistical (ordinary kriging and co-kriging). The study was conducted in the municipality of Bom Jardim, RJ, using a soil database with 208 sampling points. Predictive models were evaluated for sand, silt and clay fractions, pH in water and organic carbon at six depths according to the specifications of the consortium of digital soil mapping at the global level (GlobalSoilMap). Continuous covariates and categorical predictors were used and their contributions to the model assessed. Only the environmental covariates elevation, aspect, stream power index (SPI), soil wetness index (SWI), normalized difference vegetation index (NDVI), and b3/b2 band ratio were significantly correlated with soil properties. The predictive models had a mean coefficient of determination of 0.21. Best results were obtained with the geostatistical predictive models, where the highest coefficient of determination 0.43 was associated with sand properties between 60 to 100 cm deep. The use of a sparse data set of soil properties for digital mapping can explain only part of the spatial variation of these properties. The results may be related to the sampling density and the quantity and quality of the environmental covariates and predictive models used.

Comparação do uso de modelos digitais de elevação em mapeamento digital de solos em Dois Irmãos, RS, Brasil

Os modelos digitais de elevação (MDEs) são fontes fundamentais para correlacionar a ocorrência e distribuição de solos com a paisagem pelo mapeamento digital de solos (MDS). A influência dos tipos e das resoluções dos MDEs na capacidade de predição dos modelos preditores de classes de solo ainda é pouco estudada. Neste estudo, foram avaliados e comparados os efeitos de diferentes MDEs na predição de ocorrência de unidades de mapeamento de solo (UM). Foram correlacionados 12 atributos do terreno derivados de diferentes MDEs com a ocorrência de UM. Os MDEs utilizados foram os oriundos dos projetos SRTM v4.1, ASTER GDEM v2, TOPODATA e Brasil em Relevo, e os MDEs gerados a partir de curvas de nível na escala de 1:50.000, com resoluções de 30 e 90 m. Os modelos preditores foram treinados por árvore de decisão (Simple Cart) com dados amostrados em 4.280 pontos aleatórios contendo informações dos solos extraídos de um mapa convencional de solos na escala 1:20.000 e 12 atributos do terreno derivados de seis MDEs com tamanhos de pixel de 30 e 90 m. A validação dos modelos preditores de UM foi realizada com a totalidade dos dados da área. Os atributos do terreno que melhor explicaram a ocorrência das UM foram elevação, declividade, comprimento de fluxo e orientação das vertentes. Os MDEs com tamanho de pixel de 30 m geraram correlações solo-paisagem menos acuradas. Os modelos preditores mais acurados e com maior número de UM estimadas foram os gerados a partir dos MDEs com resolução espacial de 90 m (SRTM v4.1 e CN90), sendo esses os MDEs mais indicados para o MDS, quando predominarem relevos plano e suave ondulado.

Mapeamento digital de atributos: granulometria e matéria orgânica do solo utilizando espectroscopia de de reflectância difusa

A espectroscopia de reflectância difusa (ERD) pode ser utilizada como alternativa para quantificação de atributos como granulometria e matéria orgânica do solo (MOS). Essa técnica pode ser opção para quantificar esses atributos em grande volume de amostras de solos, visto ser rápida, com menor custo e sem a geração de resíduos químicos. O objetivo deste estudo foi desenvolver modelos usando análise de regressão linear múltipla para predizer o teor de argila, areia, silte e MOS, utilizando dados de ERD em uma área de relevo e geologia complexa localizada na região central do Rio Grande do Sul. No estudo, foram utilizadas 303 amostras coletadas na profundidade de 0,00-0,20 m para determinar os teores de argila, areia, silte e MOS por meio da análise laboratorial e de reflectância espectral. O desempenho dos modelos de predição apresentaram bons resultados, com capacidade de explicação da variância de 77 e 72 % para areia e argila, respectivamente. Mesmo com a complexidade geológica e pedológica, os resultados evidenciaram que a técnica é promissora, sendo possível a aplicação dessa técnica para predição da granulometria e teor de MOS.

COMPARAÇÃO DE ESQUEMAS DE AMOSTRAGEM PARA TREINAMENTO DE MODELOS PREDITORES NO MAPEAMENTO DIGITAL DE CLASSES DE SOLOS

Os modelos preditores usados no mapeamento digital de solos (MDS) precisam ser treinados com dados que captem ao máximo a variação dos atributos do terreno e dos solos, a fim de gerar correlações adequadas entre as variáveis ambientais e a ocorrência dos solos. Para avaliar a acurácia desses modelos, tem sido constatado o uso de diferentes métodos de avaliação da acurácia no MDS. Os objetivos deste estudo foram comparar o uso de três esquemas de amostragem para treinar algoritmo de árvore de classificação (CART) e avaliar a capacidade de predição dos modelos gerados por meio de quatro métodos. Foram utilizados os esquemas de amostragem: aleatório simples; proporcional à área de cada unidade de mapeamento de solos (UM); e estratificado pelo número de UM. Os métodos de avaliação testados foram: aparente, divisão percentual, validação cruzada com 10 subconjuntos e reamostragem com sete conjuntos de dados independentes. As acurácias dos modelos estimadas pelos métodos foram comparadas com as acurácias mensuradas obtidas pela comparação dos mapas gerados, a partir de cada esquema de amostragem, com o mapa convencional de solos na escala 1:50.000. Os esquemas de amostragem influenciaram na quantidade de UMs preditas e na acurácia dos modelos e dos mapas gerados. Os esquemas de amostragem proporcional e estratificada resultaram mapas digitais menos acurados, e a acurácia dos modelos variou conforme o método de avaliação empregado. A amostragem aleatória resultou no mapa digital mais acurado e apresentou valores da acurácia semelhantes para todos os métodos de avaliação testados.

Spatial analysis of erythrocyte membrane fluctuations by digital holographic microscopy.

Red blood cell (RBC) membrane fluctuations provide important insights into cell states. We present a spatial analysis of red blood cell membrane fluctuations by using digital holographic microscopy (DHM). This interferometric and dye-free technique, possessing nanometric axial and microsecond temporal sensitivities enables to measure cell membrane fluctuations (CMF) on the whole cell surface. DHM acquisition is combined with a model which allows extracting the membrane fluctuation amplitude, while taking into account cell membrane topology. Uneven distribution of CMF amplitudes over the RBC surface is observed, showing maximal values in a ring corresponding to the highest points on the RBC torus as well as in some scattered areas in the inner region of the RBC. CMF amplitudes of 35.9+/-8.9 nm and 4.7+/-0.5 nm (averaged over the cell surface) were determined for normal and ethanol-fixed RBCs, respectively.

SELEÇÃO DE DENSIDADE DE AMOSTRAGEM COM BASE EM DADOS DE ÁREAS JÁ MAPEADAS PARA TREINAMENTO DE MODELOS DE ÁRVORE DE DECISÃO NO MAPEAMENTO DIGITAL DE SOLOS

Para estudar técnicas de amostragem, úteis ao mapeamento digital de solos (MDS), objetivou-se avaliar o efeito da variação da densidade de pontos amostrais com base em dados de áreas já mapeadas por métodos tradicionais na acurácia dos modelos de árvores de decisão (AD) para a geração de mapas de solos por MDS. Em duas bacias hidrográficas no noroeste do Rio Grande do Sul, usou-se, como referência, antigos mapas convencionais de solos na escala 1:50.000. A partir do modelo digital de elevação do terreno e da rede hidrográfica, foram gerados mapas das variáveis preditoras: elevação, declividade, curvatura, comprimento de fluxo, acúmulo de fluxo, índice de umidade topográfica e distância euclideana de rios. A escolha dos locais dos pontos amostrais foi aleatória e testaram-se densidades amostrais que variaram de 0,1 a 4 pontos/ha. O treinamento dos modelos foi realizado no software Weka, gerando-se modelos preditores usando diferentes tamanhos do nó final da AD para obter AD com tamanhos distintos. Quando não se controlou o tamanho das AD, o aumento da densidade de amostragem resultou no aumento da concordância com os mapas básicos de referências e no aumento do número de unidades de mapeamento preditas. Nas AD com tamanho controlado, o aumento da densidade de amostragem não influenciou a concordância com os mapas de referência e interferiu muito pouco no número de unidades de mapeamento preditas.

Round robin test: wear of nine dental restorative materials in six different wear simulators - supplement to the round robin test of 2005.

OBJECTIVE: The purpose of the present study was to submit the same materials that were tested in the round robin wear test of 2002/2003 to the Alabama wear method. METHODS: Nine restorative materials, seven composites (belleGlass, Chromasit, Estenia, Heliomolar, SureFil, Targis, Tetric Ceram) an amalgam (Amalcap) and a ceramic (IPS Empress) have been submitted to the Alabama wear method for localized and generalized wear. The test centre did not know which brand they were testing. Both volumetric and vertical loss had been determined with an optical sensor. After completion of the wear test, the raw data were sent to IVOCLAR for further analysis. The statistical analysis of the data included logarithmic transformation of the data, the calculation of relative ranks of each material within each test centre, measures of agreement between methods, the discrimination power and coefficient of variation of each method as well as measures of the consistency and global performance for each material. RESULTS: Relative ranks of the materials varied tremendously between the test centres. When all materials were taken into account and the test methods compared with each other, only ACTA agreed reasonably well with two other methods, i.e. OHSU and ZURICH. On the other hand, MUNICH did not agree with the other methods at all. The ZURICH method showed the lowest discrimination power, ACTA, IVOCLAR and ALABAMA localized the highest. Material-wise, the best global performance was achieved by the leucite reinforced ceramic material Empress, which was clearly ahead of belleGlass, SureFil and Estenia. In contrast, Heliomolar, Tetric Ceram and especially Chromasit demonstrated a poor global performance. The best consistency was achieved by SureFil, Tetric Ceram and Chromasit, whereas the consistency of Amalcap and Heliomolar was poor. When comparing the laboratory data with clinical data, a significant agreement was found for the IVOCLAR and ALABAMA generalized wear method. SIGNIFICANCE: As the different wear simulator settings measure different wear mechanisms, it seems reasonable to combine at least two different wear settings to assess the wear resistance of a new material.

Multiple Geotechnological Tools Applied to Digital Mapping of Tropical Soils

ABSTRACT In recent years, geotechnologies as remote and proximal sensing and attributes derived from digital terrain elevation models indicated to be very useful for the description of soil variability. However, these information sources are rarely used together. Therefore, a methodology for assessing and specialize soil classes using the information obtained from remote/proximal sensing, GIS and technical knowledge has been applied and evaluated. Two areas of study, in the State of São Paulo, Brazil, totaling approximately 28.000 ha were used for this work. First, in an area (area 1), conventional pedological mapping was done and from the soil classes found patterns were obtained with the following information: a) spectral information (forms of features and absorption intensity of spectral curves with 350 wavelengths -2,500 nm) of soil samples collected at specific points in the area (according to each soil type); b) obtaining equations for determining chemical and physical properties of the soil from the relationship between the results obtained in the laboratory by the conventional method, the levels of chemical and physical attributes with the spectral data; c) supervised classification of Landsat TM 5 images, in order to detect changes in the size of the soil particles (soil texture); d) relationship between classes relief soils and attributes. Subsequently, the obtained patterns were applied in area 2 obtain pedological classification of soils, but in GIS (ArcGIS). Finally, we developed a conventional pedological mapping in area 2 to which was compared with a digital map, ie the one obtained only with pre certain standards. The proposed methodology had a 79 % accuracy in the first categorical level of Soil Classification System, 60 % accuracy in the second category level and became less useful in the categorical level 3 (37 % accuracy).

Screening of illegal intracorporeal containers ("body packing"): is abdominal radiography sufficiently accurate? A comparative study with low-dose CT.

PURPOSE: To evaluate the diagnostic performance of abdominal radiography in the detection of illegal intracorporeal containers (hereafter, packets), with low-dose computed tomography (CT) as the reference standard. MATERIALS AND METHODS: This study was approved by the institutional ethical review board, with written informed consent. From July 2007 to July 2010, 330 people (296 men, 34 women; mean age, 32 years [range, 18-55 years]) suspected of having ingested drug packets underwent supine abdominal radiography and low-dose CT. The presence or absence of packets at abdominal radiography was reported, with low-dose CT as the reference standard. The density and number of packets (≤ 12 or >12) at low-dose CT were recorded and analyzed to determine whether those variables influence interpretation of results at abdominal radiography. RESULTS: Packets were detected at low-dose CT in 53 (16%) suspects. Sensitivity of abdominal radiography for depiction of packets was 0.77 (41 of 53), and specificity was 0.96 (267 of 277). The packets appeared isoattenuated to the bowel contents at low-dose CT in 16 (30%) of the 53 suspects with positive results. Nineteen (36%) of the 53 suspects with positive low-dose CT results had fewer than 12 packets. Packets that were isoattenuated at low-dose CT and a low number of packets (≤12) were both significantly associated with false-negative results at abdominal radiography (P = .004 and P = .016, respectively). CONCLUSION: Abdominal radiography is mainly limited by low sensitivity when compared with low-dose CT in the screening of people suspected of carrying drug packets. Low-dose CT is an effective imaging alternative to abdominal radiography.

Digital holographic microscopy: a noninvasive contrast imaging technique allowing quantitative visualization of living cells with subwavelength axial accuracy.

We have developed a digital holographic microscope (DHM), in a transmission mode, especially dedicated to the quantitative visualization of phase objects such as living cells. The method is based on an original numerical algorithm presented in detail elsewhere [Cuche et al., Appl. Opt. 38, 6994 (1999)]. DHM images of living cells in culture are shown for what is to our knowledge the first time. They represent the distribution of the optical path length over the cell, which has been measured with subwavelength accuracy. These DHM images are compared with those obtained by use of the widely used phase contrast and Nomarski differential interference contrast techniques.

Predictors of endocarditis in isolates from cultures of blood following dental extractions in rats with periodontal disease.

Rats with periodontitis and catheter-induced aortic valve vegetations underwent dental extractions. Cultures of blood obtained 1 min later showed polymicrobial bacteremia in 19 of 19 rats, mostly due to viridans streptococci (18 of 19), Morganella (15 of 19), group G streptococci (13 of 19), and Staphylococcus aureus (10 of 19). Viridans streptococci circulated in higher numbers than did group G streptococci and S. aureus (P less than .01). Three days after dental extractions, 18 of 20 rats had endocarditis. Fifteen (83%) of 18 infections were due to group G streptococci, 9 (50%) of 18 were due to S. aureus, and 2 (11%) of 18 were due to viridans streptococci (P less than .05). In vitro, adherence to platelet-fibrin matrices of endocarditis strain 8 of group G streptococcus was two times greater than that of endocarditis strain S. aureus 23 and three to four times greater than that of Streptococcus sanguis 44 and Morganella morganii 93 (P less than 10(-5)). The inoculum size that produced endocarditis in 90% of rats after iv challenge was 10(5) cfu for group G streptococcus strain 8 and 10(7) for S. sanguis 44.

Desafios do modelo brasileiro de inclusão digital pela escola

Este artigo discute os rumos da política pública de inclusão digital nas escolas com base nos resultados da pesquisa de avaliação de impacto e de processo do Projeto UCA-Total (Um Computador por Aluno) realizada em cinco municípios onde foi implementado no decorrer de 2010 e 2011. A avaliação de impacto, de caráter longitudinal, foi feita através de um survey domiciliar aplicado em duas ondas. A pesquisa de processo associou diversas metodologias qualitativas, como grupos focais, entrevistas e visitas a campo. Limita-se aqui aos resultados derivados da pesquisa de painel, que revelam o baixo nível de aproveitamento do Projeto e um padrão de funcionamento bastante divergente em razão de vantagens e debilidades locais. Seu enorme potencial não foi até hoje completamente aproveitado.