Acquisition models in intraoperative positron surface imaging

PURPOSE: Intraoperative imaging aims at identifying residual tumor during surgery. Positron Surface Imaging (PSI) is one of the solutions to help surgeons in a better detection of resection margins of brain tumor, leading to an improved patient outcome. This system relies on a tracked freehand beta probe, using [Formula: see text]F-based radiotracer. Some acquisition models have been proposed in the literature in order to enhance image quality, but no comparative validation study has been performed for PSI. METHODS: In this study, we investigated the performance of different acquisition models by considering validation criteria and normalized metrics. We proposed a reference-based validation framework to perform the comparative study between acquisition models and a basic method. We estimated the performance of several acquisition models in light of four validation criteria: efficiency, computational speed, spatial accuracy and tumor contrast. RESULTS: Selected acquisition models outperformed the basic method, albeit with the real-time aspect compromised. One acquisition model yielded the best performance among all according to the validation criteria: efficiency (1-Spe: 0.1, Se: 0.94), spatial accuracy (max Dice: 0.77) and tumor contrast (max T/B: 5.2). We also found out that above a minimum threshold value of the sampling rate, the reconstruction quality does not vary significantly. CONCLUSION: Our method allowed the comparison of different acquisition models and highlighted one of them according to our validation criteria. This novel approach can be extended to 3D datasets, for validation of future acquisition models dedicated to intraoperative guidance of brain surgery

Association of plasma Aβ40/Aβ42 ratio and brain Aβ accumulation: testing a whole-brain PLS-VIP in individuals at risk of Alzheimer's disease

Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares, in unraveling the association between plasma Aβ42/Aβ40 ratio and an extensive set of brain regions characterized through molecular imaging of Aβ accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma Aβ42/40 ratio was associated with Aβ-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted - including the central executive and salience networks - which likely have a selective vulnerability to incipient Aβ accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions

Spectroscopic and photometric studies of low-metallicity star-forming dwarf galaxies. I. SBS 1129+576

Spectroscopy and V,I CCD photometry of the dwarf irregular galaxy SBS 1129+576 are presented for the first time. The CCD images reveal a chain of compact H II regions within the elongated low-surface-brightness (LSB) component of the galaxy. Star formation takes place mainly in two high-surface-brightness H II regions. The mean (V-I) colour of the LSB component in the surface brightness interval between 23 and 26 mag/sq.arcsec is relatively blue ~0.56+/-0.03 mag, as compared to the (V-I)~0.9-1.0 for the majority of known dwarf irregular and blue compact dwarf (BCD) galaxies. Spectroscopy shows that the galaxy is among the most metal-deficient galaxies with an oxygen abundance 12+log(O/H)= 7.36+/-0.10 in the brightest H II region and 7.48+/-0.12 in the second brightest H II region, or 1/36 and 1/28 of the solar value, respectively. Hbeta and Halpha emission lines and Hdelta and Hgamma absorption lines are detected in a large part of the LSB component. We use two extinction-insensitive methods based on the equivalent widths of (1) emission and (2) absorption Balmer lines to put constraints on the age of the stellar populations in the galaxy. In addition, we use two extinction-dependent methods based on (3) the spectral energy distribution (SED) and (4) the (V-I) colour. The observed properties of the LSB component can be reproduced by a stellar population forming continuously since 10 Gyr ago, provided that the star formation rate has increased during the last 100 Myr by a factor of 6 to 50 and no extinction is present. However, the observational properties of the LSB component can be reproduced equally well by continuous star formation which started not earlier than 100 Myr ago and stopped at 5 Myr, if some extinction is assumed.(Abridged)Comment: 17 pages, 12 figures, Accepted for publication in A&

Comparing six evolutionary population synthesis models through spectral synthesis on galaxies

We compare six popularly used evolutionary population synthesis (EPS) models (BC03, CB07, Ma05, GALEV, GRASIL, Vazdekis/Miles) through fitting the full optical spectra of six representative types of galaxies (star-forming and composite galaxies, Seyfert 2s, LINERs, E+A and early-type galaxies), which are taken from the Sloan Digital Sky Survey (SDSS). Throughout our paper, we use the simple stellar populations (SSPs) from each EPS model and the software STARLIGHT to do our fits. Our main results are: Using different EPS models the resulted numerical values of contributed light fractions change obviously, even though the dominant populations are consistent. The stellar population synthesis does depend on the selection of age and metallicity, while it does not depend on the stellar evolution track much. The importance of young populations decreases from star-forming, composite, Seyfert 2, LINER to early-type galaxies, and E+A galaxies lie between composite galaxies and Seyfert 2s in most cases. We conclude that different EPS models do derive different stellar populations, so that it is not reasonable to directly compare stellar populations estimated from different EPS models. To get reliable results, we should use the same EPS model for the compared samples.Comment: 13 pages, 4 figures, accepted for publication in A&

Spectroscopic study of blue compact galaxies III. Empirical population synthesis

This is the third paper of a series dedicated to the study of the star formation rates, star formation histories, metallicities and dust contents of a sample of blue compact galaxies (BCGs). We constrain the stellar contents of 73 blue compact galaxies by analyzing their continuum spectra and the equivalent widths of strong stellar absorption features using a technique of empirical population synthesis based on a library of observed star-cluster spectra. Our results indicate that blue compact galaxies are typically age-composite stellar systems; in addition to young stars, intermediate-age and old stars contribute significantly to the 5870 A continuum emission of most galaxies in our sample. The stellar populations of blue compact galaxies also span a variety of metallicities. The ongoing episodes of star formation started typically less than a billion years ago. Some galaxies may be undergoing their first global episode of star formation, while for most galaxies in our sample, older stars are found to contribute up to half the optical emission. Our results suggest that BCGs are primarily old galaxies with discontinuous star formation histories. The absorption equivalent widths measured in the synthetic spectra range from typically 1.5 A for Halpha, to 2 -- 5 A for Hbeta, Hgamma, and Hdelta. The implied accurate measurements of emission-line intensities will be used in a later study to constrain the star formation rates and gas-phase chemical element abundances of blue compact galaxies.Comment: 23 pages, 5 figures, accepted for publication in Astronomy and Astrophysic

Analysis of adequacy levels for human resources improvement within primary health care framework in Africa

Human resources in health care system in sub-Saharan Africa are generally picturing a lack of adequacy between expected skills from the professionals and health care needs expressed by the populations. It is, however, possible to analyse these various lacks of adequacy related to human resource management and their determinants to enhance the effectiveness of the health care system. From two projects focused on nurse professionals within the health care system in Central Africa, we present an analytic grid for adequacy levels looking into the following aspects: - adequacy between skills-based profiles for health system professionals, quality of care and service delivery (health care system /medical standards), needs and expectations from the populations, - adequacy between allocation of health system professionals, quality of care and services delivered (health care system /medical standards), needs and expectations from the populations, - adequacy between human resource management within health care system and medical standards, - adequacy between human resource management within education/teaching/training and needs from health care system and education sectors, - adequacy between basic and on-going education and realities of tasks expected and implemented by different categories of professionals within the health care system body, - adequacy between intentions for initial and on-going trainings and teaching programs in health sciences for trainers (teachers/supervisors/health care system professionals/ directors (teaching managers) of schools...). This tool is necessary for decision-makers as well as for health care system professionals who share common objectives for changes at each level of intervention within the health system. Setting this adequacy implies interdisciplinary and participative approaches for concerned actors in order to provide an overall vision of a more broaden system than health district, small island with self-rationality, and in which they operate

Rpb1 Sumoylation in Response to UV Radiation or Transcriptional Impairment in Yeast

Covalent modifications of proteins by ubiquitin and the Small Ubiquitin-like MOdifier (SUMO) have been revealed to be involved in a plethora of cellular processes, including transcription, DNA repair and DNA damage responses. It has been well known that in response to DNA damage that blocks transcription elongation, Rpb1, the largest subunit of RNA polymerase II (Pol II), is ubiquitylated and subsequently degraded in mammalian and yeast cells. However, it is still an enigma regarding how Pol II responds to damaged DNA and conveys signal(s) for DNA damage-related cellular processes. We found that Rpb1 is also sumoylated in yeast cells upon UV radiation or impairment of transcription elongation, and this modification is independent of DNA damage checkpoint activation. Ubc9, an E2 SUMO conjugase, and Siz1, an E3 SUMO ligase, play important roles in Rpb1 sumoylation. K1487, which is located in the acidic linker region between the C-terminal domain and the globular domain of Rpb1, is the major sumoylation site. Rpb1 sumoylation is not affected by its ubiquitylation, and vice versa, indicating that the two processes do not crosstalk. Abolishment of Rpb1 sumoylation at K1487 does not affect transcription elongation or transcription coupled repair (TCR) of UV-induced DNA damage. However, deficiency in TCR enhances UV-induced Rpb1 sumoylation, presumably due to the persistence of transcription-blocking DNA lesions in the transcribed strand of a gene. Remarkably, abolishment of Rpb1 sumoylation at K1487 causes enhanced and prolonged UV-induced phosphorylation of Rad53, especially in TCR-deficient cells, suggesting that the sumoylation plays a role in restraining the DNA damage checkpoint response caused by transcription-blocking lesions. Our results demonstrate a novel covalent modification of Rpb1 in response to UV induced DNA damage or transcriptional impairment, and unravel an important link between the modification and the DNA damage checkpoint response

Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins

In an attempt to improve TRAIL's (tumor necrosis factor-related apoptosis-inducing ligand) tumor selective activity a variant was designed, in which the three TRAIL protomers are expressed as a single polypeptide chain (scTRAIL). By genetic fusion with a single-chain antibody fragment (scFv) recognizing the extracellular domain of ErbB2, we further equipped scTRAIL with tumor-targeting properties. We studied tumor targeting and apoptosis induction of scFv–scTRAIL in comparison with non-targeted scTRAIL. Importantly, the tumor antigen-targeted scTRAIL fusion protein showed higher apoptotic activity in vitro, with a predominant action by TRAIL-R2 signaling. Pharmacokinetic studies revealed increased plasma half-life of the targeted scTRAIL fusion protein compared with scTRAIL. In vivo studies in a mouse tumor model with xenotransplanted Colo205 cells confirmed greater response to the ErbB2-specific scTRAIL fusion protein compared with non-targeted scTRAIL both under local and systemic application regimen. Together, in vitro and in vivo data give proof of concept of higher therapeutic activity of tumor-targeted scFv–scTRAIL molecules. Further, we envisage that through targeting of scTRAIL, potential side effects should be minimized. We propose that scFv-mediated tumor targeting of single-chain TRAIL represents a promising strategy to improve TRAIL's antitumoral action and to minimize potential unwanted actions on normal tissues