Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC-MRI of mice.

Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time-activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration-time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and 18F-FDG respectively to ascertain the technique's validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies.This work was funded by an MRC studentship and travel to PSMR 2013 was funded by the EU COST action for PET/MR.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.nima.2013.08.07

Defective Mitochondrial Function In Vivo in Skeletal Muscle in Adults with Down's Syndrome: A P-31-MRS Study

Down’s syndrome (DS) is a developmental disorder associated with intellectual disability (ID). We have previously shown that people with DS engage in very low levels of exercise compared to people with ID not due to DS. Many aspects of the DS phenotype, such as dementia, low activity levels and poor muscle tone, are shared with disorders of mitochondrial origin, and mitochondrial dysfunction has been demonstrated in cultured DS tissue. We undertook a phosphorus magnetic resonance spectroscopy ((31)P-MRS) study in the quadriceps muscle of 14 people with DS and 11 non-DS ID controls to investigate the post-exercise resynthesis kinetics of phosphocreatine (PCr), which relies on mitochondrial respiratory function and yields a measure of muscle mitochondrial function in vivo. We found that the PCr recovery rate constant was significantly decreased in adults with DS compared to non-DS ID controls (1.7±0.1 min(−1) vs 2.1±0.1 min(−1) respectively) who were matched for physical activity levels, indicating that muscle mitochondrial function in vivo is impaired in DS. This is the first study to investigate mitochondrial function in vivo in DS using (31)P-MRS. Our study is consistent with previous in vitro studies, supporting a theory of a global mitochondrial defect in DS

A third cluster of red supergiants in the vicinity of the massive cluster RSGC3

Recent studies have shown that the area around the massive, obscured cluster RSGC3 may harbour several clusters of red supergiants. In this paper, we analyse a clump of photometrically selected red supergiant candidates 20' south of RSGC3 in order to confirm the existence of another of these clusters. Using medium-resolution infrared spectroscopy around 2.27 microns, we derived spectral types and velocities along the line of sight for the selected candidates, confirming their nature and possible association. We find a compact clump of eight red supergiants and four other candidates at some distance, all of them spectroscopically confirmed red supergiants. The majority of these objects must form an open cluster, which we name Alicante 10. Because of the high reddening and strong field contamination, the cluster sequence is not clearly seen in 2MASS or GPS-UKIDSS. From the observed sources, we derive E(J-Ks)=2.6 and d~6 kpc. Although the cluster is smaller than RSGC3, it has an initial mass in excess of 10000 solar masses, and it seems to be part of the RSGC3 complex. With the new members this association already has 35 spectroscopically confirmed red supergiants, confirming its place as one of the most active sites of recent stellar formation in the Galaxy.Comment: Accepted for publication on A&

Variations on Debris Disks II. Icy Planet Formation as a Function of the Bulk Properties and Initial Sizes of Planetesimals

We describe comprehensive calculations of the formation of icy planets and debris disks at 30-150 AU around 1-3 solar mass stars. Disks composed of large, strong planetesimals produce more massive planets than disks composed of small, weak planetesimals. The maximum radius of icy planets ranges from roughly 1500 km to 11,500 km. The formation rate of 1000 km objects - `Plutos' - is a useful proxy for the efficiency of icy planet formation. Plutos form more efficiently in massive disks, in disks with small planetesimals, and in disks with a range of planetesimal sizes. Although Plutos form throughout massive disks, Pluto production is usually concentrated in the inner disk. Despite the large number of Plutos produced in many calculations, icy planet formation is inefficient. At the end of the main sequence lifetime of the central star, Plutos contain less than 10% of the initial mass in solid material. This conclusion is independent of the initial mass in the disk or the properties of planetesimals. Debris disk formation coincides with the formation of planetary systems containing Plutos. As Plutos form, they stir leftover planetesimals to large velocities. A cascade of collisions then grinds the leftovers to dust, forming an observable debris disk. In disks with small (< 1-10 km) planetesimals, collisional cascades produce luminous debris disks with maximum luminosity roughly 0.01 times the stellar luminosity. Disks with larger planetesimals produce much less luminous debris disks. Observations of debris disks around A-type and G-type stars strongly favor models with small planetesimals. In these models, our predictions for the time evolution and detection frequency of debris disks agree with published observations. We suggest several critical observations that can test key features of our calculations.Comment: 61 pages of text, 24 tables, and 34 figures; submitted to ApJS; comments welcome; revised version accepted to ApJS, changed text, modified tables, added references, no major changes to conclusion

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P &lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Global impact of nitrate photolysis in sea-salt aerosol on NOx, OH, and O3 in the marine boundary layer

Recent field studies have suggested that sea-salt particulate nitrate (NITs) photolysis may act as a significant local source of nitrogen oxides (NOx) over oceans. We present a study of the global impact of this process on oxidant concentrations in the marine boundary layer (MBL) using the GEOS-Chem model, after first updating the model to better simulate observed gas-particle phase partitioning of nitrate in the marine boundary layer. Model comparisons with long-term measurements of NOx from the Cape Verde Atmospheric Observatory (CVAO) in the eastern tropical North Atlantic provide support for an in situ source of NOx from NITs photolysis, with NITs photolysis coefficients about 25-50 times larger than corresponding HNO3 photolysis coefficients. Short-term measurements of nitrous acid (HONO) at this location show a clear daytime peak, with average peak mixing ratios ranging from 3 to 6 pptv. The model reproduces the general shape of the diurnal HONO profile only when NITs photolysis is included, but the magnitude of the daytime peak mixing ratio is under-predicted. This under-prediction is somewhat reduced if HONO yields from NITs photolysis are assumed to be close to unity. The combined NOx and HONO analysis suggests that the upper limit of the ratio of NITs : HNO3 photolysis coefficients is about 100. The largest simulated relative impact of NITs photolysis is in the tropical and subtropical marine boundary layer, with peak local enhancements ranging from factors of 5 to 20 for NOx, 1.2 to 1.6 for OH, and 1.1 to 1.3 for ozone. Since the spatial extent of the sea-salt aerosol (SSA) impact is limited, global impacts on NOx, ozone, and OH mass burdens are small ( ∼ 1-3 %). We also present preliminary analysis showing that particulate nitrate photolysis in accumulation-mode aerosols (predominantly over continental regions) could lead to ppbv-level increases in ozone in the continental boundary layer. Our results highlight the need for more comprehensive long-term measurements of NOx, and related species like HONO and sea-salt particulate nitrate, to better constrain the impact of particulate nitrate photolysis on marine boundary layer oxidant chemistry. Further field and laboratory studies on particulate nitrate photolysis in other aerosol types are also needed to better understand the impact of this process on continental boundary layer oxidant chemistry

Effects of affective picture viewing on postural control

<p>Abstract</p> <p>Background</p> <p>Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion.</p> <p>Results</p> <p>The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics.</p> <p>Conclusion</p> <p>Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior.</p

Molecular Gas in the z=1.2 Ultraluminous Merger GOODS J123634.53+621241.3

We report the detection of CO(2-1) emission from the z=1.2 ultraluminous infrared galaxy (ULIRG) GOODS J123634.53+621241.3 (also known as the sub-millimeter galaxy GN26). These observations represent the first discovery of high-redshift CO emission using the new Combined Array for Research in Millimeter-Wave Astronomy (CARMA). Of all high-redshift (z>1) galaxies within the GOODS-North field, this source has the largest far-infrared (FIR) flux observed in the Spitzer 70um and 160um bands. The CO redshift confirms the optical identification of the source, and the bright CO(2-1) line suggests the presence of a large molecular gas reservoir of about 7x10^10 M(sun). The infrared-to-CO luminosity ratio of L(IR)/L'(CO) = 80+/-30 L(sun) (K Km/s pc^2)^-1 is slightly smaller than the average ratio found in local ULIRGs and high-redshift sub-millimeter galaxies. The short star-formation time scale of about 70 Myr is consistent with a starburst associated with the merger event and is much shorter than the time scales for spiral galaxies and estimates made for high-redshift galaxies selected on the basis of their B-z and z-K colors.Comment: Accepted for publication in ApJ Letter