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1.
IEEE/ACM Trans Comput Biol Bioinform ; 16(5): 1508-1514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135366

RESUMO

Genome-wide association studies (GWAS) link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date, such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses (e.g., tensor-based morphometry; TBM) may help better localize statistical effects. This can lead to $10^{13}$1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.


Assuntos
Biologia Computacional/métodos , Estudo de Associação Genômica Ampla/métodos , Neuroimagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Encéfalo/diagnóstico por imagem , Bases de Dados Factuais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
2.
J Zoo Wildl Med ; 48(3): 645-658, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28920821

RESUMO

The aim of this study was to determine if ferritin is a reliable biomarker of iron overload disorder (IOD) progression and hemochromatosis in the Sumatran rhinoceros (Dicerorhinus sumatrensis) by developing a species-specific ferritin assay and testing historically banked samples collected from rhinos that did and did not die of hemochromatosis. Ferritin extracted from Sumatran rhino liver tissue was used to generate antibodies for the Enzyme Immunoassay. Historically banked Sumatran rhino serum samples (n = 298) obtained from six rhinos in US zoos (n = 290); five rhinos at the Sumatran Rhino Conservation Centre in Sungai Dusun, Malaysia (n = 5); and two rhinos in Sabah, Malaysia (n = 3) were analyzed for ferritin concentrations. Across all US zoo samples, serum ferritin concentrations ranged from 348 to 7,071 ng/ml, with individual means ranging from 1,267 (n = 25) to 2,604 ng/ml (n = 36). The ferritin profiles were dynamic, and all rhinos exhibited spikes in ferritin above baseline during the sampling period. The rhino with the highest mean ferritin concentration did not die of hemochromatosis and exhibited only mild hemosiderosis postmortem. A reproductive female exhibited decreases and increases in serum ferritin concurrent with pregnant and nonpregnant states, respectively. Mean (±SD) serum ferritin concentration for Sumatran rhinos in Malaysia was high (4,904 ± 4,828 ng/ml) compared to that for US zoo rhinos (1,835 ± 495 ng/ml). However, those in Sabah had lower ferritin concentrations (1,025 ± 52.7 ng/ml) compared to those in Sungai Dusun (6,456 ± 4,941 ng/ml). In conclusion, Sumatran rhino serum ferritin concentrations are dynamic, and increases often are not associated with illness or hemochromatosis. Neither a specific pattern nor the individual's overall mean ferritin concentration can be used to accurately assess IOD progression or diagnose hemochromatosis in this rhino species.


Assuntos
Ferritinas/sangue , Hemocromatose/veterinária , Sobrecarga de Ferro/veterinária , Perissodáctilos/sangue , Animais , Biomarcadores/sangue , Feminino , Hemocromatose/sangue , Sobrecarga de Ferro/sangue , Fígado/química , Masculino , Reprodutibilidade dos Testes , Especificidade da Espécie
3.
Epilepsy Behav ; 13(1): 139-43, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18396109

RESUMO

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.


Assuntos
Amobarbital/administração & dosagem , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Lateralidade Funcional/fisiologia , Idioma , Adulto , Epilepsia/cirurgia , Feminino , Humanos , Hipnóticos e Sedativos , Testes de Linguagem/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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