Convection enhanced delivery and \u3ci\u3ein vivo\u3c/i\u3e imaging of polymeric nanoparticles for the treatment of malignant glioma

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells demonstrated. Convection enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

100 hours of astronomy at the Mexican northern border

Instrumentatio

Femtoscopy of pp collisions at sqrt[s]=0.9 and 7\ua0TeV at the LHC with two-pion Bose-Einstein correlations

We report on the high statistics two-pion correlation functions from pp collisions at root s = 0.9 TeV and root s = 7 TeV, measured by the ALICE experiment at the Large Hadron Collider. The correlation functions as well as the extracted source radii scale with event multiplicity and pair momentum. When analyzed in the same multiplicity and pair transverse momentum range, the correlation is similar at the two collision energies. A three-dimensional femtoscopic analysis shows an increase of the emission zone with increasing event multiplicity as well as decreasing homogeneity lengths with increasing transverse momentum. The latter trend gets more pronounced as multiplicity increases. This suggests the development of space-momentum correlations, at least for collisions producing a high multiplicity of particles. We consider these trends in the context of previous femtoscopic studies in high-energy hadron and heavy-ion collisions and discuss possible underlying physics mechanisms. Detailed analysis of the correlation reveals an exponential shape in the outward and longitudinal directions, while the sideward remains a Gaussian. This is interpreted as a result of a significant contribution of strongly decaying resonances to the emission region shape. Significant nonfemtoscopic correlations are observed, and are argued to be the consequence of "mini-jet"-like structures extending to low p(t). They are well reproduced by the Monte-Carlo generators and seen also in pi(+)pi(-) correlations

ALICE: Physics Performance Report, Volume II

ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark\u2013gluon plasma in nucleus\u2013nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries. The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb\u2013Pb collisions (dNch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus\u2013nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies. The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC. Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate. The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517\u20131763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators. The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton\u2013proton, proton\u2013nucleus, and nucleus\u2013nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes