Reconstruction of the Corticospinal Tract in Patients with Motor-Eloquent High-Grade Gliomas Using Multilevel Fiber Tractography Combined with Functional Motor Cortex Mapping

BACKGROUND AND PURPOSE: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms. MATERIALS AND METHODS: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE ¼ 5000/78 ms, voxel size ¼ 2 × 2 × 2 mm3, 1 volume at b ¼ 0 s/mm2, 32 volumes at b ¼ 1000 s/mm2). DTI, constrained spherical deconvolution, and multilevel fiber tractography–based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested. RESULTS: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold ¼ 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold ¼ 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold ¼ 26,485 mm3, 6308 mm3, and 4270 mm3). CONCLUSIONS: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy.</p

Opportunistic osteoporosis screening in multi-detector CT images via local classification of textures.

Our study proposed an automatic pipeline for opportunistic osteoporosis screening using 3D texture features and regional vBMD using multi-detector CT images. A combination of different local and global texture features outperformed the global vBMD and showed high discriminative power to identify patients with vertebral fractures. INTRODUCTION Many patients at risk for osteoporosis undergo computed tomography (CT) scans, usable for opportunistic (non-dedicated) screening. We compared the performance of global volumetric bone mineral density (vBMD) with a random forest classifier based on regional vBMD and 3D texture features to separate patients with and without osteoporotic fractures. METHODS In total, 154 patients (mean age 64 ± 8.5, male; n = 103) were included in this retrospective single-center analysis, who underwent contrast-enhanced CT for other reasons than osteoporosis screening. Patients were dichotomized regarding prevalent vertebral osteoporotic fractures (noFX, n = 101; FX, n = 53). Vertebral bodies were automatically segmented, and trabecular vBMD was calculated with a dedicated phantom. For 3D texture analysis, we extracted gray-level co-occurrence matrix Haralick features (HAR), histogram of gradients (HoG), local binary patterns (LBP), and wavelets (WL). Fractured vertebrae were excluded for texture-feature and vBMD data extraction. The performance to identify patients with prevalent osteoporotic vertebral fractures was evaluated in a fourfold cross-validation. RESULTS The random forest classifier showed a high discriminatory power (AUC = 0.88). Parameters of all vertebral levels significantly contributed to this classification. Importantly, the AUC of the proposed algorithm was significantly higher than that of volumetric global BMD alone (AUC = 0.64). CONCLUSION The presented classifier combining 3D texture features and regional vBMD including the complete thoracolumbar spine showed high discriminatory power to identify patients with vertebral fractures and had a better diagnostic performance than vBMD alone

T2-Weighted Dixon Turbo Spin Echo for Accelerated Simultaneous Grading of Whole-Body Skeletal Muscle Fat Infiltration and Edema in Patients With Neuromuscular Diseases

Objective The assessment of fatty infiltration and edema in the musculature of patients with neuromuscular diseases (NMDs) typically requires the separate performance of T-1-weighted and fat-suppressed T-2-weighted sequences. T-2-weighted Dixon turbo spin echo (TSE) enables the generation of T-2-weighted fat- and water-separated images, which can be used to assess both pathologies simultaneously. The present study examines the diagnostic performance of T-2-weighted Dixon TSE compared with the standard sequences in 10 patients with NMDs and 10 healthy subjects. Methods Whole-body magnetic resonance imaging was performed including T-1-weighted Dixon fast field echo, T-2-weighted short-tau inversion recovery, and T-2-weighted Dixon TSE. Fatty infiltration and intramuscular edema were rated by 2 radiologists using visual semiquantitative rating scales. To assess intermethod and interrater agreement, weighted Cohen's coefficients were calculated. Results The ratings of fatty infiltration showed high intermethod and high interrater agreement (T-1-weighted Dixon fast field echo vs T-2-weighted Dixon TSE fat image). The evaluation of edematous changes showed high intermethod and good interrater agreement (T-2-weighted short-tau inversion recovery vs T-2-weighted Dixon TSE water image). Conclusions T-2-weighted Dixon TSE imaging is an alternative for accelerated simultaneous grading of whole-body skeletal muscle fat infiltration and edema in patients with NMDs

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Extensive release of methane from Arctic seabed west of Svalbard during summer 2014 does not influence the atmosphere

© 2016. American Geophysical Union. All Rights Reserved. We find that summer methane (CH4) release from seabed sediments west of Svalbard substantially increases CH4 concentrations in the ocean but has limited influence on the atmospheric CH4 levels. Our conclusion stems from complementary measurements at the seafloor, in the ocean, and in the atmosphere from land-based, ship and aircraft platforms during a summer campaign in 2014. We detected high concentrations of dissolved CH4 in the ocean above the seafloor with a sharp decrease above the pycnocline. Model approaches taking potential CH4 emissions from both dissolved and bubble-released CH4 from a larger region into account reveal a maximum flux compatible with the observed atmospheric CH4 mixing ratios of 2.4-3.8 nmol m-2 s-1. This is too low to have an impact on the atmospheric summer CH4 budget in the year 2014. Long-term ocean observatories may shed light on the complex variations of Arctic CH4 cycles throughout the year.The project MOCA- Methane Emissions from the Arctic OCean to the Atmosphere: Present and Future Climate Effects is funded by the Research Council of Norway, grant no.225814 CAGE – Centre for Arctic Gas Hydrate, Environment and Climate research work was supported by the Research Council of Norway through its Centres of Excellence funding scheme grant no. 223259. Nordic Center of Excellence eSTICC (eScience Tool for Investigating Climate Change in northern high latitudes) funded by Nordforsk, grant no. 57001

Variations of tropospheric methane over Japan during 1988–2010

We present observations of CH4 concentrations from the lower to upper troposphere (LT and UT) over Japan during 1988–2010 based on aircraft measurements from the Tohoku University (TU). The analysis is aided by simulation results using an atmospheric chemistry transport model (i.e. ACTM). Tropospheric CH4 over Japan shows interannual and seasonal variations that are dependent on altitudes, primarily reflecting differences in air mass origins at different altitudes. The long-term trend and interannual variation of CH4 in the LT are consistent with previous reports of measurements at surface baseline stations in the northern hemisphere. However, those in the UT show slightly different features from those in the LT. In the UT, CH4 concentrations show a seasonal maximum in August due to efficient transport of air masses influenced by continental CH4 sources, while LT CH4 reaches its seasonal minimum during summer due to enhanced chemical loss. Vertical profiles of the CH4 concentrations also vary with season, reflecting the seasonal cycles at the respective altitudes. In summer, transport of CH4-rich air from Asian regions elevates UT CH4 levels, forming a uniform vertical profile above the mid-troposphere. On the other hand, CH4 decreases nearly monotonically with altitude in winter–spring. The ACTM simulations with different emission scenarios reproduce general features of the tropospheric CH4 variations over Japan. Tagged tracer simulations using the ACTM indicate substantial contributions of CH4 sources in South Asia and East Asia to the summertime high CH4 values observed in the UT. This suggests that our observations over Japan are highly sensitive to CH4 emission signals particularly from Asia

The Impact of Changing Medicaid Enrollments on New Mexico's Immunization Program

Background: Immunizations are an important component to pediatric primary care. New Mexico is a relatively poor and rural state which has sometimes struggled to achieve and maintain its childhood immunization rates. We evaluated New Mexico’s immunization rates between 1996 and 2006. Specifically, we examined the increase in immunization rates between 2002 and 2004, and how this increase may have been associated with Medicaid enrollment levels, as opposed to changes in government policies concerning immunization practices. Methods and Findings: This study examines trends in childhood immunization coverage rates relative to Medicaid enrollment among those receiving Temporary Assistance for Needy Families (TANF) in New Mexico. Information on health policy changes and immunization coverage was obtained from state governmental sources and the National Immunization Survey. We found statistically significant correlations varying from 0.86 to 0.93 between immunization rates and Medicaid enrollment. Conclusions: New Mexico’s improvement and subsequent deterioration in immunization rates corresponded with changing Medicaid coverage, rather than the state’s efforts to change immunization practices. Maintaining high Medicaid enrollmen

Massive Peatland Carbon Banks Vulnerable to Rising Temperatures

Peatlands contain one-third of the world’s soil carbon (C). If destabilized, decomposition of this vast C bank could accelerate climate warming; however, the likelihood of this outcome remains unknown. Here, we examine peatland C stability through five years of whole-ecosystem warming and two years of elevated atmospheric carbon dioxide concentrations (eCO2). Warming exponentially increased methane (CH4) emissions and enhanced CH4 production rates throughout the entire soil profile; although surface CH4 production rates remain much greater than those at depth. Additionally, older deeper C sources played a larger role in decomposition following prolonged warming. Most troubling, decreases in CO2:CH4 ratios in gas production, porewater concentrations, and emissions, indicate that the peatland is becoming more methanogenic with warming. We observed limited evidence of eCO2 effects. Our results suggest that ecosystem responses are largely driven by surface peat, but that the vast C bank at depth in peatlands is responsive to prolonged warming

Down Regulation of a Matrix Degrading Cysteine Protease Cathepsin L, by Acetaldehyde: Role of C/EBPα

BACKGROUND: The imbalance between extra cellular matrix (ECM) synthesis and degradation is critical aspect of various hepatic pathologies including alcohol induced liver fibrosis. This study was carried out to investigate the effect of acetaldehyde on expression of an extra cellular matrix degrading protease cathepsin L (CTSL) in HepG2 cells. METHODOLOGY AND RESULTS: We measured the enzymatic activity, protein and, mRNA levels of CTSL in acetaldehyde treated and untreated cells. The binding of CAAT enhancer binding protein α (C/EBP α) to CTSL promoter and its key role in the transcription from this promoter and conferring responsiveness to acetaldehyde was established by site directed mutagenesis, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assays and siRNA technology. Acetaldehyde treatment significantly decreased CTSL activity and protein levels in HepG2 cells. A similar decrease in the mRNA levels and promoter activity was also observed. This decrease by acetaldehyde was attributed to the fall in the liver enriched transcription factor C/EBP α levels and it's binding to the CTSL promoter. Mutagenesis of C/EBP α binding motifs revealed the key role of this factor in CTSL transcription as well as conferring responsiveness to acetaldehyde. The siRNA mediated silencing of the C/EBP α expression mimicked the effect of acetaldehyde on CTSL levels and its promoter activity. It also abolished the responsiveness of this promoter to acetaldehyde. CONCLUSION: Acetaldehyde down regulates the C/EBP α mediated CTSL expression in hepatic cell lines. The decreased expression of CTSL may at least in part contribute to ECM deposition in liver which is a hallmark of alcoholic liver fibrosis

Understanding the glacial methane cycle.

Atmospheric methane (CH4) varied with climate during the Quaternary, rising from a concentration of 375 p.p.b.v. during the last glacial maximum (LGM) 21,000 years ago, to 680 p.p.b.v. at the beginning of the industrial revolution. However, the causes of this increase remain unclear; proposed hypotheses rely on fluctuations in either the magnitude of CH4 sources or CH4 atmospheric lifetime, or both. Here we use an Earth System model to provide a comprehensive assessment of these competing hypotheses, including estimates of uncertainty. We show that in this model, the global LGM CH4 source was reduced by 28-46%, and the lifetime increased by 2-8%, with a best-estimate LGM CH4 concentration of 463-480 p.p.b.v. Simulating the observed LGM concentration requires a 46-49% reduction in sources, indicating that we cannot reconcile the observed amplitude. This highlights the need for better understanding of the effects of low CO2 and cooler climate on wetlands and other natural CH4 sources