Development and validation of a patient- tailored dose regime in myocardial perfusion imaging using conventional SPECT

Background\ud The decreasing image quality in heavier patients can be compensated by administration of a patient-specific dose in myocardial perfusion imaging (MPI) using a cadmium zinc telluride-based SPECT camera. Our aim was to determine if the same can be achieved when using a conventional SPECT camera.\ud \ud \ud Methods\ud 148 patients underwent SPECT stress MPI using a fixed Tc-99m tetrofosmin tracer dose. Measured photon counts were normalized to administered tracer dose and scan time and were correlated with body weight, body mass index, and mass per length to find the best predicting parameter. From these data, a protocol to provide constant image quality was derived, and subsequently validated in 125 new patients.\ud \ud \ud Results\ud Body weight was found to be the best predicting parameter for image quality and was used to derive a new dose formula; Aadmin (MBq) = 223·body weight (kg)0.65/Tscan (min). The measured photon counts decreased in heavier patients when using a fixed dose (P < .01) but this was no longer observed after applying a body-weight-dependent protocol (P = .20).\ud \ud \ud Conclusions\ud Application of a patient-specific protocol resulted in an image quality less depending on patient’s weight. The results are most likely independent of the type of SPECT camera used, and, hence, adoption of patient-specific dose and scan time protocols is recommended

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

BACKGROUND: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. METHODS: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. RESULTS: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). CONCLUSIONS: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics

Demystifying an unidentified EGRET source by VHE gamma-ray observations

In a novel approach in observational high-energy gamma-ray astronomy, observations carried out by imaging atmospheric Cherenkov telescopes provide necessary templates to pinpoint the nature of intriguing, yet unidentified EGRET gamma-ray sources. Using GeV-photons detected by CGRO EGRET and taking advantage of high spatial resolution images from H.E.S.S. observations, we were able to shed new light on the EGRET observed gamma-ray emission in the Kookaburra complex, whose previous coverage in the literature is somewhat contradictory. 3EGJ1420-6038 very likely accounts for two GeV gamma-ray sources (E>1 GeV), both in positional coincidence with the recently reported pulsar wind nebulae (PWN) by HESS in the Kookaburra/Rabbit complex. PWN associations at VHE energies, supported by accumulating evidence from observations in the radio and X-ray band, are indicative for the PSR/plerionic origin of spatially coincident, but still unidentified Galactic gamma-ray sources from EGRET. This not only supports the already suggested connection between variable, but unidentified low-latitude gamma-ray sources with pulsar wind nebulae (3EGJ1420-6038 has been suggested as PWN candidate previoulsy), it also documents the ability of resolving apparently confused EGRET sources by connecting the GeV emission as measured from a large-aperture space-based gamma-ray instrument with narrow field-of-view but superior spatial resolution observations by ground-based atmospheric Cherenkov telescopes, a very promising identification technique for achieving convincing individual source identifications in the era of GLAST-LAT.Comment: 4 pages, 5 figures, Accepted for publication in Astrophysics and Space Science, Proc. of "The Multi-Messenger Approach to High-Energy Gamma-ray Sources (Third Workshop on the Nature of Unidentified High-Energy Sources)", Barcelona, July 4-7, 2006, one typo correcte

Nuclear effects in the Drell-Yan process at very high energies

We study Drell-Yan (DY) dilepton production in proton(deuterium)-nucleus and in nucleus-nucleus collisions within the light-cone color dipole formalism. This approach is especially suitable for predicting nuclear effects in the DY cross section for heavy ion collisions, as it provides the impact parameter dependence of nuclear shadowing and transverse momentum broadening, quantities that are not available from the standard parton model. For p(D)+A collisions we calculate nuclear shadowing and investigate nuclear modification of the DY transverse momentum distribution at RHIC and LHC for kinematics corresponding to coherence length much longer than the nuclear size. Calculations are performed separately for transversely and longitudinally polarized DY photons, and predictions are presented for the dilepton angular distribution. Furthermore, we calculate nuclear broadening of the mean transverse momentum squared of DY dileptons as function of the nuclear mass number and energy. We also predict nuclear effects for the cross section of the DY process in heavy ion collisions. We found a substantial nuclear shadowing for valence quarks, stronger than for the sea.Comment: 46 pages, 18 figures, title changed and some discussion added, accepted for publication in PR

Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π−3\pi^+ 3\pi^- diffractive photoproduction

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

Recurrent differentiated thyroid cancer: Towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): Study protocol of a multicenter observational cohort study

Background: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.Discussion: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registration: Clinicaltrials.gov identifier: NCT01641679

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans

The human sense of smell decreases with age, and a poor sense of smell are among the most important prodromal symptoms of several neurodegenerative diseases. Recent evidence further suggests a racial difference in the sense of smell among U.S. older adults. However, no genome-wide association study (GWAS) on the sense of smell has been conducted in African-Americans (AAs). We performed the first genome-wide meta-analysis of the sense of smell among 1979 AAs and 6582 European-Americans (EAs) from three U.S. aging cohorts. In the AA population, we identified nine novel regions (KLF4-ACTL7B, RAPGEF2-FSTL5, TCF4-LOC100505474, PCDH10, KIAA1751, MYO5B, MIR320B1-CD2, NR5A2-LINC00862, SALL1-C16orf97) that were associated with the sense of smell (P &lt; 5 × 10−8). Many of these regions have been previously linked to neuropsychiatric (schizophrenia or epilepsy) or neurodegenerative (Parkinson’s or Alzheimer’s disease) diseases associated with a decreased sense of smell. In the EA population, we identified two novel loci in or near RASGRP1 and ANXA2P3 associated with sense of smell. In conclusion, this study identified several ancestry-specific loci that are associated with the sense of smell in older adults. While these findings need independent confirmation, they may lead to novel insights into the biology of the sense of smell in older adults and its relationships to neuropsychological and neurodegenerative diseases