Shortened Modified Look-Locker Inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold

Background T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients. Materials and methods The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms<T1 < 2.7 s and heart rates 40-100 bpm followed by phantom validation at 1.5T and 3T. In-vivo myocardial T1-mapping using this method and the previous gold-standard (MOLLI) was performed in 10 healthy volunteers at 1.5T and 3T, 4 volunteers with contrast injection at 1.5T, and 4 patients with recent myocardial infarction (MI) at 3T. Results We found good agreement between the average ShMOLLI and MOLLI estimates for T1 < 1200 ms. In contrast to the original method, ShMOLLI showed no dependence on heart rates for long T1 values, with estimates characterized by a constant 4% underestimation for T1 = 800-2700 ms. In-vivo, ShMOLLI measurements required 9.0 ± 1.1 s (MOLLI = 17.6 ± 2.9 s). Average healthy myocardial T1 s by ShMOLLI at 1.5T were 966 ± 48 ms (mean ± SD) and 1166 ± 60 ms at 3T. In MI patients, the T1 in unaffected myocardium (1216 ± 42 ms) was similar to controls at 3T. Ischemically injured myocardium showed increased T1 = 1432 ± 33 ms (p < 0.001). The difference between MI and remote myocardium was estimated 15% larger by ShMOLLI than MOLLI (p < 0.04) which suffers from heart rate dependencies for long T1. The in-vivo variability within ShMOLLI T1-maps was only 14% (1.5T) or 18% (3T) higher than the MOLLI maps, but the MOLLI acquisitions were twice longer than ShMOLLI acquisitions. Conclusion ShMOLLI is an efficient method that generates immediate, high-resolution myocardial T1-maps in a short breath-hold with high precision. This technique provides a valuable clinically applicable tool for myocardial tissue characterisation

Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery

Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathologic, biochemical, and/or behavioral assays. Many questions related to CTE development however remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work we attempt to address some of these questions by exploring work previously completed using single and repetitive injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology

Flinders Island spotted fever rickettsioses caused by "marmionii" strain of rickettsia honei, Eastern Australia

Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion

The Effect of Precipitates on Twinning in Magnesium Alloys

Understanding how to strengthen against twin mediated deformation is critical for controlling the mechanical properties and formability of magnesium. One route to strengthening is through precipitation of shear resistant particles. This paper presents the current understanding of how precipitate particles and (1012) twins interact in magnesium, and how this influences strength. Precipitates increase the yield stress for twin dominated deformation but none of the current models reliably predict the strengthening effect. Precipitates have never been observed to completely suppress twinning, but usually lead to an increased number of narrower twins. Precipitates are not effective in increasing the stress for twin nucleation sufficiently to preferentially activate alternative deformation modes, but the effect on the stresses for both twin propagation and growth are significant. In the propagation stage, twin tips overcome precipitates by bowing of multiple twinning dislocations. For thick twins this can probably be assisted by pile up of twinning partials behind the tip. During growth, precipitates increase the stress to propagate new twinning steps, mainly due to increasing the unrelaxed back-stress. Since nucleation, propagation, and growth of twins all have to occur before macroscopic yield, a complete model to predict the strengthening effect must consider all of these stages.</p

Dehalogenation of polychlorinated biphenyls and polybrominated diphenyl ethers using a hybrid bioinorganic catalyst

The environmentally prevalent polybrominated diphenyl ether (PBDE) #47 and polychlorinated biphenyls (PCBs) #28 and #118 were challenged for 24 hours with a novel biomass-supported Pd catalyst (BioPd0). Analysis of the products via GC/MS revealed the BioPd0 to cause the challenged compounds to undergo stepwise dehalogenation with preferential loss of the least sterically hindered halogen atom. A mass balance for PCB #28 showed that it is degraded to three dichlorobiphenyls (33.9 %), two monochlorobiphenyls (12 %), and biphenyl (30.7 %). The remaining mass was starting material. In contrast, while PCB #118 underwent degradation to yield five tetra- and five trichlorinated biphenyls; no less chlorinated products or biphenyl were detected, and the total mass of degraded products was 0.3 %. Although the BioPd0 material was developed for treatment of PCBs, a mass balance for PBDE #47 showed that the biocatalyst could prove a useful method for treatment of PBDEs. Specifically, 10 % of PBDE # 47 was converted to identifiable lower brominated congeners, predominantly the tribrominated BDE 17, and the dibrominated BDE 4, 75 % remained intact, while 15 % of the starting mass was unaccounted for

Relativity, rank and the utility of income

This is the accepted version of the following article: Rablen, M. D. (2008), Relativity, Rank and the Utility of Income. The Economic Journal, 118: 801–821, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1468-0297.2008.02143.x/abstract.Relative utility has become an important concept in several disjoint areas of economics. I present a cardinal model of income utility based on the supposition that agents care about their rank in the income distribution and that utility is subject to adaptation over time. Utility levels correspond to the Leyden Individual Welfare Function while utility differences yield a version of the prospect theory value function, thereby providing a new and shared derivation of each. I offer an explanation of some long-standing paradoxes in the wellbeing literature and an insight into the links between relative comparisons and loss aversion.ESR

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users

The Atacama Cosmology Telescope: Data Characterization and Map Making

We present a description of the data reduction and mapmaking pipeline used for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from 2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2 hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial equator. We discuss sources of statistical and systematic noise, calibration, telescope pointing, and data selection. Out of 1260 survey hours and 1024 detectors per array, 816 hours and 593 effective detectors remain after data selection for this frequency band, yielding a 38% survey efficiency. The total sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units. Atmospheric brightness fluctuations constitute the main contaminant in the data and dominate the detector noise covariance at low frequencies in the TOD. The maps were made by solving the least-squares problem using the Preconditioned Conjugate Gradient method, incorporating the details of the detector and noise correlations. Cross-correlation with WMAP sky maps, as well as analysis from simulations, reveal that our maps are unbiased at multipoles ell > 300. This paper accompanies the public release of the 148 GHz southern stripe maps from 2008. The techniques described here will be applied to future maps and data releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape