Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience.

Over the past few decades, several radiotracers have been developed for neuroimaging applications, especially in PET. Because of their low steric hindrance, PET radionuclides can be used to label molecules that are small enough to cross the blood brain barrier, without modifying their biological properties. As the use of 11C is limited by its short physical half-life (20 min), there has been an increasing focus on developing tracers labeled with 18F for clinical use. The first such tracers allowed cerebral blood flow and glucose metabolism to be measured, and the development of molecular imaging has since enabled to focus more closely on specific targets such as receptors, neurotransmitter transporters, and other proteins. Hence, PET and SPECT biomarkers have become indispensable for innovative clinical research. Currently, the treatment options for a number of pathologies, notably neurodegenerative diseases, remain only supportive and symptomatic. Treatments that slow down or reverse disease progression are therefore the subject of numerous studies, in which molecular imaging is proving to be a powerful tool. PET and SPECT biomarkers already make it possible to diagnose several neurological diseases in vivo and at preclinical stages, yielding topographic, and quantitative data about the target. As a result, they can be used for assessing patients' eligibility for new treatments, or for treatment follow-up. The aim of the present review was to map major innovative radiotracers used in neuroscience, and explain their contribution to clinical research. We categorized them according to their target: dopaminergic, cholinergic or serotoninergic systems, β-amyloid plaques, tau protein, neuroinflammation, glutamate or GABA receptors, or α-synuclein. Most neurological disorders, and indeed mental disorders, involve the dysfunction of one or more of these targets. Combinations of molecular imaging biomarkers can afford us a better understanding of the mechanisms underlying disease development over time, and contribute to early detection/screening, diagnosis, therapy delivery/monitoring, and treatment follow-up in both research and clinical settings

2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) can identify chronic lymphocytic leukaemia (CLL) stage A et stage B patients

Purpose: There is no data in the literature concerning the utility of 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in chronic lymphocytic leukaemia (CLL), except for the diagnosis of Richter\u27s transformations. The purpose of this study was to assess the potential role of FDG-PET in CLL stages A and B. Materials and methods: Thirty-five patients (61 ± 9 years; 11 women, 24 men; 8B and 27A) have benefited of a FDG-PET scan at baseline, for example, before an eventual treatment. FDG-PET scans were analyzed visually and the maximum values of the Standardised Uptake Value (SUVmax) were measured in the main lymph nodes areas. The ability of FDG-PET to differentiate stages A and B patients was evaluated by Student\u27s tests and Receiver Operating Characteristics (ROC) analysis. Results: All patients with a normal FDG-PET (n = 18) were stages A. The remaining 17 patients (9A and 8B) showed hypermetabolisms in nodal areas above (n = 17) and below (n = 9) the diaphragm, and no visceral involvement. The lymph nodes hypermetabolisms were always bilateral, and of low intensity (≤ mediastinum; 9A), or of higher intensity (≥ liver, 8B). The SUVmax of stage B (n = 8) were significantly higher than those of the 27 stages A, in all lymph nodes areas except in mediastinum. The highest intensity of FDG uptake was observed in axillary area in stages B patients (SUVmax = 2.74 ± 1.03). An axillary SUVmax of 1.33 is the most suitable value for the discrimination between stages A and B patients (ROC; AUC = 0.968; sensitivity 1.00; specificity 0.91). Conclusion: Lymph nodes hypermetabolisms are constant in the B stage, and more intense than in stage A. These anomalies are always bilateral, unlike what is observed in Richter\u27s transformation. The intensity of axillary lymph nodes FDG uptake can distinguish CLL stages A and B

A Comparison of Algorithms for the Construction of SZ Cluster Catalogues

We evaluate the construction methodology of an all-sky catalogue of galaxy clusters detected through the Sunyaev-Zel'dovich (SZ) effect. We perform an extensive comparison of twelve algorithms applied to the same detailed simulations of the millimeter and submillimeter sky based on a Planck-like case. We present the results of this "SZ Challenge" in terms of catalogue completeness, purity, astrometric and photometric reconstruction. Our results provide a comparison of a representative sample of SZ detection algorithms and highlight important issues in their application. In our study case, we show that the exact expected number of clusters remains uncertain (about a thousand cluster candidates at |b|> 20 deg with 90% purity) and that it depends on the SZ model and on the detailed sky simulations, and on algorithmic implementation of the detection methods. We also estimate the astrometric precision of the cluster candidates which is found of the order of ~2 arcmins on average, and the photometric uncertainty of order ~30%, depending on flux.Comment: Accepted for publication in A&A: 14 pages, 7 figures. Detailed figures added in Appendi

A Critical Success Factor Framework for Implementing Sustainable Innovative and Affordable Housing: A Systematic Review and Bibliometric Analysis

The actualization of affordable housing remains a challenge. This challenge is exacerbated by the increasing societal demand for the incorporation of sustainability principles into such housing types to improve levels of occupant health and well-being whilst avouching the desired levels of affordability. Innovative technologies and practices have been described as beneficial to the effectuation of sustainable affordable housing. However, knowledge concerning the deployment of innovative technologies and practices in sustainable affordable housing (sustainable, innovative, affordable housing—SIAH) delivery remains nascent. Consequently, there is a lack of a common ontology among stakeholders concerning how to realize SIAH. This study aims to contribute toward the development of this body of knowledge through the establishment of the critical success factors (CSFs) for effective SIAH implementation. To achieve this objective, a systematic review and bibliometric analysis focusing on a juxtaposition of sustainable, innovative and affordable housing concepts was carried out based on the relevant literature. This led to the identification and clustering of CSFs for these housing concepts at individual levels and as a collective (SIAH). The findings of the study consisted of the establishment of four distinct yet interrelated facets through which SIAH can be achieved holistically, namely, housing design, house element, housing production method and housing technology. A total of 127 CSFs were found to be aligned to these facets, subsequently clustered, and conclusively used for the development of a SIAH CSF framework. The most frequently occurring CSFs with predominant interconnections were the utilization of energy-efficient systems/fittings, tenure security, a comfortable and healthy indoor environment, affordable housing price in relation to income and using water-efficient systems/fittings CSFs, and establishing the emergent SIAH CSF framework. The framework in this study is useful in the documentation of SIAH features for construction projects and further studies into SIAH CSFs

A Stokes-based spectro-polarimetric analysis of the amplified spontaneous emission in a semiconductor optical amplifier

Semiconductor Optical Amplifiers (SOAs), key devices for future all-optical communication systems, are inherently polarisation-dependent, which is a major drawback for most networks applications. In spite of numerous studies carried out in order to design polarisation-insensitive structures, no complete spectro-polarimetric characterization of a SOA has been published so far. In particular, the spectral and polarimetric behaviour of the Amplified Spontaneous Emission (ASE), acting as a partly polarized broadband source, is of interest, since ASE draws from the same carrier reservoir as the amplified signal. In this paper, we present a full spectro-polarimetric characterization of ASE emitted from a commercial, strained-bulk SOA within the frame of the Stokes formalism. This formalism not only allows a determination of the degree of polarisation (DOP) of ASE directly from its Stokes vector, but also gives access to a full, spectrally resolved characterization of its polarized fraction with respect to the bias current applied to the SOA. The way the state of polarisation of that fraction is governed by the dependence of the material gain upon polarisation is spectrally resolved, quantified, and discussed. The same study is performed when a polarized signal is injected into the SOA

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

We performed a genetic association study of rare variants and single nucleotide polymorphisms (SNPs) of UCMA/GRP and OPTN genes, in French-Canadian patients with Paget's disease of bone (PDB) and in healthy controls from the same population. We reproduced the variant found in the UCMA/GRP basal promoter and tested its functionality using in vitro transient transfection assays. Interestingly, this SNP rs17152980 appears to affect the transcription level of UCMA/GRP. In addition, we have identified five rare genetic variants in UCMA/GRP gene, four of them being population-specific, although none were found to be associated with PDB. Six Tag SNPs of UCMA/GRP gene were associated with PDB, particularly the SNP rs17152980 (uncorrected P = 3.8 x 10(-3)), although not significant after Bonferroni's correction. More importantly, we replicated the strong and statistically significant genetic association of two SNPs of the OPTN gene, the rs1561570 (uncorrected P = 5.7 x 10(-7)) and the rs2095388 (uncorrected P = 4.9 x 10(-3)), With PDB. In addition, we identified a very rare variant found to be located close to the basal promoter of the OPTN gene, at -232 bp from its distal transcription start site. Furthermore, depending on the type of allele present (G or A), the binding of several important nuclear factors such as the vitamin D or the retinoic acid receptors is predicted to be altered at this position, suggesting a significant effect in the regulation of transcription of the OPTN gene. In conclusion, we identified a functional SNP located in the basal promoter of the UCMA/GRP gene which provided a weak genetic association with PDB. In addition, we replicated the strong genetic association of two already known SNPs of the OPTN gene, with PDB in a founder effect population. We also identified a very rare variant in the promoter of OPTN, and through bioinformatic analysis, identified putative transcription factor binding sites likely to affect OPTN gene transcription. (C) 2012 Elsevier Inc. All rights reserved.Fonds de la Recherche du Quebec - Sante (FRQS), Canada; Portuguese Science and Technology Foundation, Portugal [SFRH/BPD/48206/2008]; Catalyst Grant (Bone Health) from the Canadian Institutes of Health Research (Canada); CHUQ Foundation (Canada); Groupe de Recherche en Maladies Osseuses (Canada); Canadian Foundation for Innovation (Canada); FRSQ (Canada); Laval University (Canada); CHUQ (CHUL) Research Centre (Canada); Centre of Marine Sciences (CCMAR) (Portugal)info:eu-repo/semantics/publishedVersio

The pre-launch Planck Sky Model: a model of sky emission at submillimetre to centimetre wavelengths

We present the Planck Sky Model (PSM), a parametric model for the generation of all-sky, few arcminute resolution maps of sky emission at submillimetre to centimetre wavelengths, in both intensity and polarisation. Several options are implemented to model the cosmic microwave background, Galactic diffuse emission (synchrotron, free-free, thermal and spinning dust, CO lines), Galactic H-II regions, extragalactic radio sources, dusty galaxies, and thermal and kinetic Sunyaev-Zeldovich signals from clusters of galaxies. Each component is simulated by means of educated interpolations/extrapolations of data sets available at the time of the launch of the Planck mission, complemented by state-of-the-art models of the emission. Distinctive features of the simulations are: spatially varying spectral properties of synchrotron and dust; different spectral parameters for each point source; modeling of the clustering properties of extragalactic sources and of the power spectrum of fluctuations in the cosmic infrared background. The PSM enables the production of random realizations of the sky emission, constrained to match observational data within their uncertainties, and is implemented in a software package that is regularly updated with incoming information from observations. The model is expected to serve as a useful tool for optimizing planned microwave and sub-millimetre surveys and to test data processing and analysis pipelines. It is, in particular, used for the development and validation of data analysis pipelines within the planck collaboration. A version of the software that can be used for simulating the observations for a variety of experiments is made available on a dedicated website.Comment: 35 pages, 31 figure

Ultra High Energy Cosmology with POLARBEAR

Observations of the temperature anisotropy of the Cosmic Microwave Background (CMB) lend support to an inflationary origin of the universe, yet no direct evidence verifying inflation exists. Many current experiments are focussing on the CMB's polarization anisotropy, specifically its curl component (called "B-mode" polarization), which remains undetected. The inflationary paradigm predicts the existence of a primordial gravitational wave background that imprints a unique B-mode signature on the CMB's polarization at large angular scales. The CMB B-mode signal also encodes gravitational lensing information at smaller angular scales, bearing the imprint of cosmological large scale structures (LSS) which in turn may elucidate the properties of cosmological neutrinos. The quest for detection of these signals; each of which is orders of magnitude smaller than the CMB temperature anisotropy signal, has motivated the development of background-limited detectors with precise control of systematic effects. The POLARBEAR experiment is designed to perform a deep search for the signature of gravitational waves from inflation and to characterize lensing of the CMB by LSS. POLARBEAR is a 3.5 meter ground-based telescope with 3.8 arcminute angular resolution at 150 GHz. At the heart of the POLARBEAR receiver is an array featuring 1274 antenna-coupled superconducting transition edge sensor (TES) bolometers cooled to 0.25 Kelvin. POLARBEAR is designed to reach a tensor-to-scalar ratio of 0.025 after two years of observation -- more than an order of magnitude improvement over the current best results, which would test physics at energies near the GUT scale. POLARBEAR had an engineering run in the Inyo Mountains of Eastern California in 2010 and will begin observations in the Atacama Desert in Chile in 2011.Comment: 8 pages, 6 figures, DPF 2011 conference proceeding

The bolometric focal plane array of the Polarbear CMB experiment

The Polarbear Cosmic Microwave Background (CMB) polarization experiment is currently observing from the Atacama Desert in Northern Chile. It will characterize the expected B-mode polarization due to gravitational lensing of the CMB, and search for the possible B-mode signature of inflationary gravitational waves. Its 250 mK focal plane detector array consists of 1,274 polarization-sensitive antenna-coupled bolometers, each with an associated lithographed band-defining filter. Each detector's planar antenna structure is coupled to the telescope's optical system through a contacting dielectric lenslet, an architecture unique in current CMB experiments. We present the initial characterization of this focal plane