The management of intracranial pseudoaneurysms is controversial. The purpose of this study was to provide a preliminary evaluation of the clinical efficacy of a Willis covered stent specially ...designed for the intracranial vasculature in the management of a pseudoaneurysm of the cranial internal carotid artery (CICA).
Eight patients with pseudoaneurysms of the CICA were treated with use of the Willis covered stent. The flexibility of the entire stent system was gauged from the resistance met when reaching the target lesion and was categorized as no resistance, no apparent resistance, or resistance that could be overcome. The apposition of the Willis stent after deployment was scored as excellent with no endoleak, good with a small endoleak, or bad with an apparent endoleak. Follow-up angiography was performed 3 to 12 months after placement of the stent, and angiographic assessments were categorized as endoleak, stenosis of the covered segment of vessel, or occlusion of parent arteries. Follow-up clinical evaluations were also performed, and outcomes were graded as full recovery, improvement, unchanged, and aggravation.
Endovascular treatment was technically successful in all aneurysms without procedural-related complications, and all of the stents were easily navigated to the targeted lesions in the CICA. Complete resolution of the pseudoaneurysm was observed in 6 patients immediately after the procedure, and a minimal endoleak into the aneurysm persisted in 2 patients. No morbidity or mortality and no technical adverse event occurred. A follow-up angiogram confirmed complete reconstruction of the internal carotid artery, with no recurrent aneurysmal filling and no occurrence of stenosis in the area of the stent. By the final follow-up visit, 4 patients had fully recovered, 3 had improved, and 1 patient's condition was unchanged.
On the basis of our preliminary experience, the Willis covered stent specially designed for the intracranial vasculature can manage a CICA pseudoaneurysm safely and effectively, but longer follow-up and expanded clinical trials are needed.
We review the history of the South American summer monsoon (SASM) over the past ~2000 yr based on high-resolution stable isotope proxies from speleothems, ice cores and lake sediments. Our review is ...complemented by an analysis of an isotope-enabled atmospheric general circulation model (GCM) for the past 130 yr. Proxy records from the monsoon belt in the tropical Andes and SE Brazil show a very coherent behavior over the past 2 millennia with significant decadal to multidecadal variability superimposed on large excursions during three key periods: the Medieval Climate Anomaly (MCA), the Little Ice Age (LIA) and the current warm period (CWP). We interpret these three periods as times when the SASM's mean state was significantly weakened (MCA and CWP) and strengthened (LIA), respectively. During the LIA each of the proxy archives considered contains the most negative δ18O values recorded during the entire record length. On the other hand, the monsoon strength is currently rather weak in a 2000-yr historical perspective, rivaled only by the low intensity during the MCA. Our climatic interpretation of these archives is consistent with our isotope-based GCM analysis, which suggests that these sites are sensitive recorders of large-scale monsoon variations. We hypothesize that these centennial-scale climate anomalies were at least partially driven by temperature changes in the Northern Hemisphere and in particular over the North Atlantic, leading to a latitudinal displacement of the ITCZ and a change in monsoon intensity (amount of rainfall upstream over the Amazon Basin). This interpretation is supported by several independent records from different proxy archives and modeling studies. Although ENSO is the main forcing for δ18O variability over tropical South America on interannual time scales, our results suggest that its influence may be significantly modulated by North Atlantic climate variability on longer time scales. Finally, our analyses indicate that isotopic proxies, because of their ability to integrate climatic information on large spatial scales, could complement more traditional proxies such as tree rings or documentary evidence. Future climate reconstruction efforts could potentially benefit from including isotopic proxies as large-scale predictors in order to better constrain past changes in the atmospheric circulation.
A previous study conducted in Taiwan found a 100% association between HLA‐B*1502 allele and carbamazepine‐induced Stevens‐Johnson syndrome (SJS) in Han Chinese subjects, with an extremely high odds ...ratio compared with carbamazepine‐tolerant subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han Chinese subjects who had cutaneous adverse reactions induced by different antiepileptic drugs (AEDs). They were matched with 48 AED‐tolerant controls. HLA‐B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs, which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio = 17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32). Further studies in larger samples of ethnically matched subjects should be conducted to confirm the findings. Identification of genetic polymorphisms predisposing to development of AED‐induced SCR offers the possibility of avoiding these high‐risk drugs in genetically susceptible individuals.
Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large ...selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.
FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic ...lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
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•Non-steroidal agonists of FXR significantly decrease intestinal lipid absorption•FXR decreases hepatic triglycerides independently of SHP and SREBP1C•FXR activation reduces expression of three key lipogenic genes, Scd1, Lpin1, and Dgat2•Intestinal and hepatic FXR are both required to decrease hepatic triglycerides
The nuclear receptor FXR lowers hepatic triglycerides to protect against the onset of NAFLD. Clifford et al. demonstrate that activation of FXR decreases hepatic triglycerides through two distinct mechanisms. First, via bile-acid-dependent decreases in intestinal lipid absorption and second, through selective changes in lipogenesis.
In 3D nematic liquid crystals, disclination lines have a range of geometric structures. Locally, they may resemble +1/2 or −1/2 defects in 2D nematic phases, or they may have 3D twist. Here, we ...analyze the structure in terms of the director deformation modes around the disclination, as well as the nematic order tensor inside the disclination core. Based on this analysis, we construct a vector to represent the orientation of the disclination, as well as tensors to represent higher-order structure. We apply this method to simulations of a 3D disclination arch, and determine how the structure changes along the contour length. We then use this geometric analysis to investigate three types of forces acting on a disclination: Peach-Koehler forces due to external stress, interaction forces between disclination lines, and active forces. These results apply to the motion of disclination lines in both conventional and active liquid crystals.
In nematic liquid crystals, disclination lines have several geometric features, which can be characterized by vectors and tensors. Based on these features, the mechanical forces on disclination lines can be calculated.
Defect-free monolayers of graphene and hexagonal boron nitride are surprisingly permeable to thermal protons, despite being completely impenetrable to all gases. It remains untested whether small ...ions can permeate through the two-dimensional crystals. Here we show that mechanically exfoliated graphene and hexagonal boron nitride exhibit perfect Nernst selectivity such that only protons can permeate through, with no detectable flow of counterions. In the experiments, we use suspended monolayers that have few, if any, atomic-scale defects, as shown by gas permeation tests, and place them to separate reservoirs filled with hydrochloric acid solutions. Protons account for all the electrical current and chloride ions are blocked. This result corroborates the previous conclusion that thermal protons can pierce defect-free two-dimensional crystals. Besides the importance for theoretical developments, our results are also of interest for research on various separation technologies based on two-dimensional materials.
Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) ...and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
OS data were available for 912 patients. The median PFS was 3.3months (95% CI 2.9–3.6) and 6-month PFS rate was 27% (95% CI 24–30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3cm versus <3cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2months (95% CI 9.5–11.0) and 1year OS was 43% (95% CI 40–47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, ...spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.
Abstract
Line intensity mapping (LIM) provides a unique and powerful means to probe cosmic structures by measuring the aggregate line emission from all galaxies across redshift. The method is ...complementary to conventional galaxy redshift surveys that are object based and demand exquisite point-source sensitivity. The Tomographic Ionized-carbon Mapping Experiment (TIME) will measure the star formation rate during cosmic reionization by observing the redshifted C
ii
158
μ
m line (6 ≲
z
≲ 9) in the LIM regime. TIME will simultaneously study the abundance of molecular gas during the era of peak star formation by observing the rotational CO lines emitted by galaxies at 0.5 ≲
z
≲ 2. We present the modeling framework that predicts the constraining power of TIME on a number of observables, including the line luminosity function and the auto- and cross-correlation power spectra, including synergies with external galaxy tracers. Based on an optimized survey strategy and fiducial model parameters informed by existing observations, we forecast constraints on physical quantities relevant to reionization and galaxy evolution, such as the escape fraction of ionizing photons during reionization, the faint-end slope of the galaxy luminosity function at high redshift, and the cosmic molecular gas density at cosmic noon. We discuss how these constraints can advance our understanding of cosmological galaxy evolution at the two distinct cosmic epochs for TIME, starting in 2021, and how they could be improved in future phases of the experiment.
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