Predicting speech fluency and naming abilities in aphasic patients

There is a need to identify biomarkers that predict degree of chronic speech fluency/language impairment and potential for improvement after stroke. We previously showed that the Arcuate Fasciculus lesion load (AF-LL), a combined variable of lesion site and size, predicted speech fluency in patients with chronic aphasia. In the current study, we compared lesion loads of such a structural map (i.e., AF-LL) with those of a functional map [i.e., the functional gray matter lesion load (fGM-LL)] in their ability to predict speech fluency and naming performance in a large group of patients. The fGM map was constructed from functional brain images acquired during an overt speaking task in a group of healthy elderly controls. The AF map was reconstructed from high-resolution diffusion tensor images also from a group of healthy elderly controls. In addition to these two canonical maps, a combined AF-fGM map was derived from summing fGM and AF maps. Each canonical map was overlaid with individual lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production and fluency to calculate a functional and structural lesion load value for each patient, and to regress these values with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability; however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed that AF lesion load was best at stratifying patients into severe and non-severe outcome groups with 96% accuracy for speech fluency and 90% accuracy for naming. An AF-LL of greater than 4 cc was the critical threshold that determined poor fluency and naming outcomes, and constitutes the severe outcome group. Thus, surrogate markers of impairments have the potential to predict outcomes and can be used as a stratifier in experimental studies

The Progression of β-amyloid Deposition in the Frontal Cortex of the Aged Canine

Brains from 41 aged canines (≥10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of β-amyloid (Aβ) in frontal cortex. We classified the Aβ patterns into four distinct types. Type I was characterized by small, faint deposits of Aβ in deep cortical layers. Type II consisted of diffuse deposits of Aβ mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the Aβ distribution pattern between the Old canines (10–15 years, n=22) and the Very Old canines (\u3e15 years, n=19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (Pβ deposition in canine frontal cortex is a progressive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer layers. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of β-amyloid with an isomerized aspartic acid residue at position 7, indicating that these deposits had been present for some time. We also observed fiber-like Aβ immunoreactivity within regions of diffuse Aβ deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers may represent a very early form of neuritic change that precede tau hyperphosphorylation or develop by an alternative pathway

Progress in Computational Simulation of Earthquakes

GeoFEST(P) is a computer program written for use in the QuakeSim project, which is devoted to development and improvement of means of computational simulation of earthquakes. GeoFEST(P) models interacting earthquake fault systems from the fault-nucleation to the tectonic scale. The development of GeoFEST( P) has involved coupling of two programs: GeoFEST and the Pyramid Adaptive Mesh Refinement Library. GeoFEST is a message-passing-interface-parallel code that utilizes a finite-element technique to simulate evolution of stress, fault slip, and plastic/elastic deformation in realistic materials like those of faulted regions of the crust of the Earth. The products of such simulations are synthetic observable time-dependent surface deformations on time scales from days to decades. Pyramid Adaptive Mesh Refinement Library is a software library that facilitates the generation of computational meshes for solving physical problems. In an application of GeoFEST(P), a computational grid can be dynamically adapted as stress grows on a fault. Simulations on workstations using a few tens of thousands of stress and displacement finite elements can now be expanded to multiple millions of elements with greater than 98-percent scaled efficiency on over many hundreds of parallel processors (see figure)

Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

BACKGROUND: Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. METHODS: We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. RESULTS: In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular density within the tumors. By contrast, transient exogenous treatment of MDA-MB-231 xenografts with rhSulf2 was not sufficient to inhibit or reverse tumor growth. CONCLUSION: These data indicate that in vivo progression of human breast cancer xenografts can be inhibited with sulfatase expression, and therapeutic effect requires constant delivery at the tumor site. Our results support a direct effect of sulfatases on tumor growth or invasion, rather than an effect in the stromal compartment

The Contribution of Neuropsychoanalysis to Clinical Practice in Psychiatry

Our patients usually present with unwanted feelings - ‘Dr. I’m feeling depressed/anxious, etc.’ Do we treat these feelings as psychological abnormalities needing to be extinguished or as indicators of underlying problems that need addressing? To help answer this, psychiatrists may benefit from developments in Affective Neuroscience. One such development is Panksepp’s model of the brain, which describes seven basic emotional systems (BES)

QuakeSim 2.0

QuakeSim 2.0 improves understanding of earthquake processes by providing modeling tools and integrating model applications and various heterogeneous data sources within a Web services environment. QuakeSim is a multisource, synergistic, data-intensive environment for modeling the behavior of earthquake faults individually, and as part of complex interacting systems. Remotely sensed geodetic data products may be explored, compared with faults and landscape features, mined by pattern analysis applications, and integrated with models and pattern analysis applications in a rich Web-based and visualization environment. Integration of heterogeneous data products with pattern informatics tools enables efficient development of models. Federated database components and visualization tools allow rapid exploration of large datasets, while pattern informatics enables identification of subtle, but important, features in large data sets. QuakeSim is valuable for earthquake investigations and modeling in its current state, and also serves as a prototype and nucleus for broader systems under development. The framework provides access to physics-based simulation tools that model the earthquake cycle and related crustal deformation. Spaceborne GPS and Inter ferometric Synthetic Aperture (InSAR) data provide information on near-term crustal deformation, while paleoseismic geologic data provide longerterm information on earthquake fault processes. These data sources are integrated into QuakeSim's QuakeTables database system, and are accessible by users or various model applications. UAVSAR repeat pass interferometry data products are added to the QuakeTables database, and are available through a browseable map interface or Representational State Transfer (REST) interfaces. Model applications can retrieve data from Quake Tables, or from third-party GPS velocity data services; alternatively, users can manually input parameters into the models. Pattern analysis of GPS and seismicity data has proved useful for mid-term forecasting of earthquakes, and for detecting subtle changes in crustal deformation. The GPS time series analysis has also proved useful as a data-quality tool, enabling the discovery of station anomalies and data processing and distribution errors. Improved visualization tools enable more efficient data exploration and understanding. Tools provide flexibility to science users for exploring data in new ways through download links, but also facilitate standard, intuitive, and routine uses for science users and end users such as emergency responders

Coordenadores do Título IX como burocratas de nível de rua nas escolas dos Estados Unidos: Desafios para enfrentar a discriminação sexual na era #MeToo

Sex discrimination in educational contexts is an ongoing problem despite the passage of Title IX in 1972. Many schools have not aligned their policies with new laws protecting students from bullying and harassment, and many professionals are unaware of their new obligations in regards to new state regulations. This article presents the findings from semi-structured interviews with 10 participants reporting on the roles and responsibilities of Title IX coordinators in their K-12 school districts. Title IX coordinators were difficult to locate and recruitment was a challenge in this study. However, our findings indicate a strong alignment with Lipsky’s concept of “street-level bureaucrats” (1971, 2010). We found that these school administrators had autonomy and discretion in interpreting and enacting their duties, however they lacked time, information, and other resources necessary to respond properly to the stated duties in their position. They reported spending very little time on Title IX-related duties, many felt under-supported and under-prepared, and few had comprehensive understanding of their responsibilities. We conclude with recommendations for policy and practice regarding the training and supports of Title IX coordinators and related gender equity efforts in K-12 schools.La discriminación sexual en contextos educativos es un problema continuo a pesar de la aprobación del Título IX en 1972. Muchas escuelas no han alineado sus políticas con nuevas leyes que protegen a los estudiantes de la intimidación y el acoso, y muchos profesionales desconocen sus nuevas obligaciones con respecto a regulaciones estatales Este artículo presenta los hallazgos de entrevistas semiestructuradas con 10 participantes que informan sobre los roles y responsabilidades de los coordinadores del Título IX en sus distritos escolares K-12. Los coordinadores del Título IX fueron difíciles de localizar y el reclutamiento fue un desafío en este estudio. Sin embargo, nuestros hallazgos indican una fuerte alineación con el concepto de Lipsky de "burócratas a nivel de calle" (1971, 2010). Descubrimos que estos administradores escolares tenían autonomía y discreción para interpretar y cumplir sus deberes, sin embargo, carecían de tiempo, información y otros recursos necesarios para responder adecuadamente a los deberes establecidos en su puesto. Informaron que dedicaron muy poco tiempo a los deberes relacionados con el Título IX, muchos se sintieron insuficientemente apoyados y poco preparados, y pocos tenían una comprensión exhaustiva de sus responsabilidades. Concluimos con recomendaciones de políticas y prácticas con respecto a la capacitación y el apoyo de los coordinadores del Título IX y los esfuerzos relacionados con la equidad de género en las escuelas K-12.A discriminação sexual em ambientes educacionais é um problema contínuo, apesar da aprovação do Título IX em 1972. Muitas escolas não alinharam suas políticas com novas leis que protegem os alunos de intimidação e assédio, e muitos profissionais desconhecem seus direitos. novas obrigações com relação aos regulamentos estaduais Este artigo apresenta os resultados de entrevistas semi-estruturadas com 10 participantes que relatam os papéis e responsabilidades dos coordenadores do Título IX em seus distritos escolares K-12. Os coordenadores do Título IX foram difíceis de localizar e o recrutamento foi um desafio neste estudo. No entanto, nossos resultados indicam um forte alinhamento com o conceito de "burocratas de rua" de Lipsky (1971, 2010). Descobrimos que esses administradores escolares tinham autonomia e discrição para interpretar e cumprir suas obrigações, no entanto, eles não tinham tempo, informações e outros recursos necessários para responder adequadamente aos deveres estabelecidos em sua posição. Eles relataram que gastaram muito pouco tempo em tarefas relacionadas ao Título IX, muitos se sentiram insuficientemente apoiados e despreparados, e poucos tinham uma compreensão abrangente de suas responsabilidades. Concluímos com recomendações e práticas de políticas relacionadas à formação e apoio de coordenadores do Título IX e esforços relacionados à eqüidade de gênero nas escolas do ensino fundamental e médio

Integration of Holonomic Thinking in Educational Leader-ship Development Courses

Educational leaders are prime observers of their school performance and progress. As leaders and active participants in the steps towards school improvement, they must take into consideration diverse stakeholders’ opinions, ideas and beliefs, and technical aspects such as data analysis while engaging in the decision-making process. This practice can be enhanced by considering the circumstances and all stakeholders involved from a holonomic viewpoint rather than an egocentric viewpoint. This article explores the holonomic conceptual platform and its strategies as a conduit to broaden emergent school leaders’ perspectives

Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure.

Two gene clusters are tightly linked in a narrow region of chromosome 22q11.23: the macrophage migration inhibitory factor (MIF) gene family and the glutathione S-transferase theta class. Within 120 kb in this region, two 30-kb deletions reach high frequencies in human populations. This gives rise to four haplotypic arrangements, which modulate the number of genes in both families. The variable patterns of linkage disequilibrium (LD) between these copy number variants (CNVs) in diverse human populations remain poorly understood. We analyzed 2469 individuals belonging to 27 human populations with different ethnic origins. Then we correlated the genetic variability of 22q11.23 CNVs with environmental variables. We confirmed an increasing strength of LD from Africa to Asia and to Europe. Further, we highlighted strongly significant correlations between the frequency of one of the haplotypes and pigmentation-related variables: skin color (R2=0.675, P<0.001), distance from the equator (R2=0.454, P<0.001), UVA radiation (R2=0.439, P<0.001), and UVB radiation (R2=0.313, P=0.002). The fact that all MIF-related genes are retained on this haplotype and the evidences gleaned from experimental systems seem to agree with the role of MIF-related genes in melanogenesis. As such, we propose a model that explains the geographic and ethnic distribution of 22q11.23 CNVs among human populations, assuming that MIF-related gene dosage could be associated with adaptation to low UV radiatio