Automated template-based brain localization and extraction for fetal brain MRI reconstruction.

Most fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant voxels of low-resolution (LR) images to enhance the quality of inter-slice motion correction and image reconstruction. Consequently the fetal brain needs to be localized and extracted as a first step, which is usually a laborious and time consuming manual or semi-automatic task. We have proposed in this work to use age-matched template images as prior knowledge to automatize brain localization and extraction. This has been achieved through a novel automatic brain localization and extraction method based on robust template-to-slice block matching and deformable slice-to-template registration. Our template-based approach has also enabled the reconstruction of fetal brain images in standard radiological anatomical planes in a common coordinate space. We have integrated this approach into our new reconstruction pipeline that involves intensity normalization, inter-slice motion correction, and super-resolution (SR) reconstruction. To this end we have adopted a novel approach based on projection of every slice of the LR brain masks into the template space using a fusion strategy. This has enabled the refinement of brain masks in the LR images at each motion correction iteration. The overall brain localization and extraction algorithm has shown to produce brain masks that are very close to manually drawn brain masks, showing an average Dice overlap measure of 94.5%. We have also demonstrated that adopting a slice-to-template registration and propagation of the brain mask slice-by-slice leads to a significant improvement in brain extraction performance compared to global rigid brain extraction and consequently in the quality of the final reconstructed images. Ratings performed by two expert observers show that the proposed pipeline can achieve similar reconstruction quality to reference reconstruction based on manual slice-by-slice brain extraction. The proposed brain mask refinement and reconstruction method has shown to provide promising results in automatic fetal brain MRI segmentation and volumetry in 26 fetuses with gestational age range of 23 to 38 weeks

Primary cortical folding in the human newborn: an early marker of later functional development

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early ‘endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB

Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit1

One-sentence summary for table of contents: Recommendations are needed for management of potential laboratory exposure to a Biosafety Level 4 pathogen

Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Thermal effects in high density polyethylene and low density polyethylene at high hydrostatic pressures

The temperature changes as a result of rapid hydrostatic pressure applications are reported for high density polyethylene (HDPE) and low density polyethylene (LDPE) in the reference temperature range from 298 to 423 K and in the pressure range from 13.8 to 200 MN m −2 . The adiabatic temperature changes were found to be a function of pressure and temperature. A curve fitting analysis showed that the empirical curve (∂/∂ P ) = ab (Δ P ) b−1 described the experimental thermoelastic coefficients obtained from the experiments. The data were analyzed by determining the predicted thermoelastic coefficients derived from the Thomson equation (∂/∂ P ) θ = α T 0 /ϱ C p . The experimental and predicted Grüneisen parameter γ T were also determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44687/1/10853_2005_Article_BF01132919.pd

Novel Structurally Designed Vaccine for S. aureus α-Hemolysin: Protection against Bacteremia and Pneumonia

Staphylococcus aureus (S. aureus) is a human pathogen associated with skin and soft tissue infections (SSTI) and life threatening sepsis and pneumonia. Efforts to develop effective vaccines against S. aureus have been largely unsuccessful, in part due to the variety of virulence factors produced by this organism. S. aureus alpha-hemolysin (Hla) is a pore-forming toxin expressed by most S. aureus strains and reported to play a key role in the pathogenesis of SSTI and pneumonia. Here we report a novel recombinant subunit vaccine candidate for Hla, rationally designed based on the heptameric crystal structure. This vaccine candidate, denoted AT-62aa, was tested in pneumonia and bacteremia infection models using S. aureus strain Newman and the pandemic strain USA300 (LAC). Significant protection from lethal bacteremia/sepsis and pneumonia was observed upon vaccination with AT-62aa along with a Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) that is currently in clinical trials. Passive transfer of rabbit immunoglobulin against AT-62aa (AT62-IgG) protected mice against intraperitoneal and intranasal challenge with USA300 and produced significant reduction in bacterial burden in blood, spleen, kidney, and lungs. Our Hla-based vaccine is the first to be reported to reduce bacterial dissemination and to provide protection in a sepsis model of S. aureus infection. AT62-IgG and sera from vaccinated mice effectively neutralized the toxin in vitro and AT62-IgG inhibited the formation of Hla heptamers, suggesting antibody-mediated neutralization as the primary mechanism of action. This remarkable efficacy makes this Hla-based vaccine a prime candidate for inclusion in future multivalent S. aureus vaccine. Furthermore, identification of protective epitopes within AT-62aa could lead to novel immunotherapy for S. aureus infection

Portfolio manager ownership and mutual fund performance

This paper examines the association between a mutual fund manager's personal fund investment and mutual fund performance. Newly-released managerial ownership disclosures reveal that fund ownership varies across mutual fund managers and, in many instances, is quite large. I find that mutual fund returns are increasing in the level of managerial fund investment, consistent with managerial ownership realigning decision-maker and shareholder interests. Also consistent with the reduction of agency costs, I find that managerial ownership is inversely related to fund turnover, which could affect both tax and trading costs. However, I do not find any association between portfolio manager ownership and a mutual fund's tax burden