Refined Structure of Metastable Ice XVII from Neutron Diffraction Measurements

The structure of the recently identified metastable ice XVII, obtained by release of hydrogen from the C$_0$ D$_2$O-H$_2$ compound (filled ice), has been accurately measured by neutron powder diffraction. The diffraction pattern is indexed with a hexagonal cell and can be refined with space group $P6_122$ so to obtain accurate values of the oxygen and deuterium positions. The values of the lattice constants at three temperatures between 25 to 100 K are reported, and their behavior is compared with that of ice Ih. Ice XVII is a porous solid that, if exposed to H$_2$ gas, may adsorb a substantial amount of it. Monitoring this effect at a constant temperature of 50 K, we have observed that the two lattice constants show opposite behavior, $a$ increases and $c$ decreases, with the volume showing a linear increase. At temperatures higher than 130 K the metastability of this form of porous ice is lost and the sample transforms into ice Ih

Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT

Hemorrhagic transformation in acute ischemic stroke patients and atrial fibrillation: time to initiation of anticoagulants and outcome

Background: In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results: HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions: In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability

Anticoagulation After Stroke in Patients With Atrial Fibrillation : To Bridge or Not With Low-Molecular-Weight Heparin?

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.Peer reviewe

White matter integrity correlates with cognition and disease severity in Fabry disease: an MR Diffusion Tensor Imaging study.

White matter pathology, visualised as white matter hyperintensities on MRI, is a common central nervous system manifestation of Fabry disease, affecting 42-81% of patients. Diffusion tensor imaging MRI is a sensitive technique to quantify microstructural damage within the white matter. We evaluated the pattern of diffusion tensor imaging abnormalities in Fabry disease, and its correlation with cognitive impairment, mood, anxiety, disease severity and plasma Lyso-Gb3 levels in 31 patients with genetically-proven Fabry disease and 19 age-matched healthy controls. We obtained average values of fractional anisotropy and mean diffusivity within the white matter, and performed voxelwise analysis with Tract-Based Spatial Statistics. We assessed processing speed, executive function, anxiety, depression and disease severity using validated scales and scores. The mean age (% male) of the Fabry disease cohort and for the healthy control groups were 44.1 (45%) and 37.4 (53%), respectively. Compared to healthy controls, the mean average white matter fractional anisotropy was lower in Fabry disease patients (0.423 (SD 0.23) vs. 0.446 (SD 0.16), p=0.002), while mean average white matter mean diffusivity was higher in Fabry disease patients (749 x 10-6 mm2/s (SD 32 x 10-6) vs 720 x 10-6 mm2/s (SD 21 x 10-6), p=0.004). Voxelwise statistics showed that these diffusion abnormalities (for both fractional anisotropy and mean diffusivity) were anatomically widespread. In patients, average white matter fractional anisotropy and white matter lesion volume showed strong correlations with Digit Symbol Coding Test score (r=0.558, p=0.001; and r=-0.634, p=<0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r=-0.661, p=<0.001). Finally, average white matter mean diffusivity showed a strong correlation with plasma Lyso-Gb3 levels (r=0.559, p=0.001). In Fabry disease white matter diffusion tensor imaging measures correlate with processing speed, disease severity and plasma Lyso-Gb3, making them promising quantitative biomarkers for monitoring disease severity and progression

Exact modeling of the flexible slewing link

The exact eigenfunctions for the slewing link are found, taking into account a rotating inertia at the base and a payload at the tip. These derive from two equivalent formulations (pseudoclamped and pseudopinned) of the boundary value problem relative to the flexible slewing beam. The exactness of the solution makes it possible to prove the equivalence of these two approaches, which differ in the choice of the noninertial rotating frame. The two related dynamic linear models are then found, and a change of coordinates is given. Experimental measurements validate the theoretical results