Advanced morphometric techniques applied to the study of human brain anatomy

El desarrollo de las técnicas de imágenes por resonancia magnética han permitido el estudio y cuantificación, in vivo, de los cambios que ocurren en la morfología cerebral ligados a procesos tales como el neurodesarrollo, el envejecimiento, el aprendizaje o la enfermedad. Un gran número de métodos de morfometría han sido desarrollados con el fin de extraer la información contenida en estas imágenes y traducirla en indicadores de forma o tamaño, tales como el volumen o el grosor cortical; marcadores que son posteriormente empleados para encontrar diferencias estadísticas entre poblaciones de sujetos o realizar correlaciones entre la morfología cerebral y, por ejemplo, la edad o la severidad de determinada enfermedad. A pesar de la amplia variedad de biomarcadores y metodologías de morfometría, muchos estudios sesgan sus hipótesis, y con ello los resultados experimentales, al empleo de un número reducido de biomarcadores o a al uso de una única metodología de procesamiento. Con el presente trabajo se pretende demostrar la importancia del empleo de diversos métodos de morfometría para lograr una mejor caracterización del proceso que se desea estudiar. En el mismo se emplea el análisis de forma para detectar diferencias, tanto globales como locales, en la morfología del tálamo entre pacientes adolescentes con episodios tempranos de psicosis y adolescentes sanos. Los resultados obtenidos demuestran que la diferencia de volumen talámico entre ambas poblaciones de sujetos, previamente descrita en la literatura, se debe a una reducción del volumen de la región anterior-mediodorsal y del núcleo pulvinar del tálamo de los pacientes respecto a los sujetos sanos. Además, se describe el desarrollo de un estudio longitudinal, en sujetos sanos, que emplea simultáneamente distintos biomarcadores para la caracterización y cuantificación de los cambios que ocurren en la morfología de la corteza cerebral durante la adolescencia. A través de este estudio se revela que el proceso de “alisado” que experimenta la corteza cerebral durante la adolescencia es consecuencia de una disminución de la profundidad, ligada a un incremento en el ancho, de los surcos corticales. Finalmente, esta metodología es aplicada, en un diseño transversal, para el estudio de las causas que provocan el decrecimiento tanto del grosor cortical como del índice de girificación en adolescentes con episodios tempranos de psicosis. ABSTRACT The ever evolving sophistication of magnetic resonance image techniques continue to provide new tools to characterize and quantify, in vivo, brain morphologic changes related to neurodevelopment, senescence, learning or disease. The majority of morphometric methods extract shape or size descriptors such as volume, surface area, and cortical thickness from the MRI image. These morphological measurements are commonly entered in statistical analytic approaches for testing between-group differences or for correlations between the morphological measurement and other variables such as age, sex, or disease severity. A wide variety of morphological biomarkers are reported in the literature. Despite this wide range of potentially useful biomarkers and available morphometric methods, the hypotheses and findings of the grand majority of morphological studies are biased because reports assess only one morphometric feature and usually use only one image processing method. Throughout this dissertation biomarkers and image processing strategies are combined to provide innovative and useful morphometric tools for examining brain changes during neurodevelopment. Specifically, a shape analysis technique allowing for a fine-grained assessment of regional thalamic volume in early-onset psychosis patients and healthy comparison subjects is implemented. Results show that disease-related reductions in global thalamic volume, as previously described by other authors, could be particularly driven by a deficit in the anterior-mediodorsal and pulvinar thalamic regions in patients relative to healthy subjects. Furthermore, in healthy adolescents different cortical features are extracted and combined and their interdependency is assessed over time. This study attempts to extend current knowledge of normal brain development, specifically the largely unexplored relationship between changes of distinct cortical morphological measurements during adolescence. This study demonstrates that cortical flattening, present during adolescence, is produced by a combination of age-related increase in sulcal width and decrease in sulcal depth. Finally, this methodology is applied to a cross-sectional study, investigating the mechanisms underlying the decrease in cortical thickness and gyrification observed in psychotic patients with a disease onset during adolescence.

Folding simulations of a three-stranded antiparallel β-sheet peptide

Protein folding is a grand challenge of the postgenomic era. In this paper, 58 folding events sampled during 47 molecular dynamics trajectories for a total simulation time of more than 4 μs provide an atomic detail picture of the folding of a 20-residue synthetic peptide with a stable three-stranded antiparallel β-sheet fold. The simulations successfully reproduce the NMR solution conformation, irrespective of the starting structure. The sampling of the conformational space is sufficient to determine the free energy surface and localize the minima and transition states. The statistically predominant folding pathway involves the formation of contacts between strands 2 and 3, starting with the side chains close to the turn, followed by association of the N-terminal strand onto the preformed 2–3 β-hairpin. The folding mechanism presented here, formation of a β-hairpin followed by consolidation, is in agreement with a computational study of the free energy surface of another synthetic three-stranded antiparallel β-sheet by Bursulaya and Brooks [(1999) J. Am. Chem. Soc. 121, 9947–9951]. Hence, it might hold in general for antiparallel β-sheets with short turns.

Unifying the observational diversity of isolated neutron stars via magneto-thermal evolution models

Observations of magnetars and some of the high magnetic field pulsars have shown that their thermal luminosity is systematically higher than that of classical radio-pulsars, thus confirming the idea that magnetic fields are involved in their X-ray emission. Here we present the results of 2D simulations of the fully coupled evolution of temperature and magnetic field in neutron stars, including the state-of-the-art kinetic coefficients and, for the first time, the important effect of the Hall term. After gathering and thoroughly re-analysing in a consistent way all the best available data on isolated, thermally emitting neutron stars, we compare our theoretical models to a data sample of 40 sources. We find that our evolutionary models can explain the phenomenological diversity of magnetars, high-B radio-pulsars, and isolated nearby neutron stars by only varying their initial magnetic field, mass and envelope composition. Nearly all sources appear to follow the expectations of the standard theoretical models. Finally, we discuss the expected outburst rates and the evolutionary links between different classes. Our results constitute a major step towards the grand unification of the isolated neutron star zoo.

Comparative Analysis of the Visual Performance After Cataract Surgery With Implantation of a Bifocal or Trifocal Diffractive IOL

PURPOSE: To evaluate and compare the visual, refractive, contrast sensitivity, and aberrometric outcomes with a diffractive bifocal and trifocal intraocular lens (IOL) of the same material and haptic design. METHODS: Sixty eyes of 30 patients undergoing bilateral cataract surgery were enrolled and randomly assigned to one of two groups: the bifocal group, including 30 eyes implanted with the bifocal diffractive IOL AT LISA 801 (Carl Zeiss Meditec, Jena, Germany), and the trifocal group, including eyes implanted with the trifocal diffractive IOL AT LISA tri 839 MP (Carl Zeiss Meditec). Analysis of visual and refractive outcomes, contrast sensitivity, ocular aberrations (OPD-Scan III; Nidek, Inc., Gagamori, Japan), and defocus curve were performed during a 3-month follow-up period. RESULTS: No statistically significant differences between groups were found in 3-month postoperative uncorrected and corrected distance visual acuity (P > .21). However, uncorrected, corrected, and distance-corrected near and intermediate visual acuities were significantly better in the trifocal group (P < .01). No significant differences between groups were found in postoperative spherical equivalent (P = .22). In the binocular defocus curve, the visual acuity was significantly better for defocus of -0.50 to -1.50 diopters in the trifocal group (P < .04) and -3.50 to -4.00 diopters in the bifocal group (P < .03). No statistically significant differences were found between groups in most of the postoperative corneal, internal, and ocular aberrations (P > .31), and in contrast sensitivity for most frequencies analyzed (P > .15). CONCLUSIONS: Trifocal diffractive IOLs provide significantly better intermediate vision over bifocal IOLs, with equivalent postoperative levels of visual and ocular optical quality.

"Certificate respecting the Rev. John Seccombe," 1795 August

One leaf (pages 301-302) of the August, 1795 issue of Massachusetts Magazine with an editorial regarding the authorship of Father Abbey's Will. The article identifies John Seccombe as the author based on information provided by "Thaddeus Mason, Esq. of Cambridge, the only surviving classmate, and very intimate friend of the Rev. John Seccombe."

Letter from William Croswell to Thomas L. Winthrop, 1824 August 10

Draft of a brief letter requesting Winthrop communicate an arithmetical solution to the Academy of Arts and Sciences.

Letter from William Croswell to George Ticknor, 1825 August 3

Draft of a letter requesting to borrow a treatise.

Letter from William Croswell to [William] Jenks, 1825 August 11

Draft of a letter concerning the languages of the polyglot.

Letter from William Croswell to William Phillips, 1825 August 23

Draft of a letter requesting employment at the Andover Theological Institution.

Letter from William Croswell to Isaac Winslow, 1825 August 28

Draft of a letter regarding Croswell's employment with Harvard.

Letters to Mrs. Bowker, 1828 August 9

Copy of a letter related to the settlement of debt with Bowker's father.