This article presents families of spatial discretizations of the nonlinear rotating shallow‐water equations that conserve both energy and potential enstrophy. These are based on two‐dimensional mixed ...finite‐element methods and hence, unlike some finite‐difference methods, do not require an orthogonal grid. Numerical verification of the aforementioned properties is also provided.
We present a generic algorithm for numbering and then efficiently iterating over the data values attached to an extruded mesh. An extruded mesh is formed by replicating an existing mesh, assumed to ...be unstructured, to form layers of prismatic cells. Applications of extruded meshes include, but are not limited to, the representation of three-dimensional high aspect ratio domains employed by geophysical finite element simulations. These meshes are structured in the extruded direction. The algorithm presented here exploits this structure to avoid the performance penalty traditionally associated with unstructured meshes. We evaluate the implementation of this algorithm in the Firedrake finite element system on a range of low compute intensity operations which constitute worst cases for data layout performance exploration. The experiments show that having structure along the extruded direction enables the cost of the indirect data accesses to be amortized after 10–20 layers as long as the underlying mesh is well ordered. We characterize the resulting spatial and temporal reuse in a representative set of both continuous-Galerkin and discontinuous-Galerkin discretizations. On meshes with realistic numbers of layers the performance achieved is between 70 and 90 % of a theoretical hardware-specific limit.
We present and characterize a narrow-linewidth external-cavity diode laser at 2 μm, and show that it represents a low-cost, high-performance alternative to fiber lasers for research into 2 μm ...photonic technologies for next-generation gravitational-wave detectors. A linewidth of 20 kHz for a 10 ms integration time was measured without any active stabilization, with frequency noise of ∼ 15 Hz/Hz between 3 kHz and 100 kHz. This performance is suitable for the generation of quantum squeezed light, and we measure intensity noise comparable to that of master oscillators used in current gravitational wave interferometers. The laser wavelength is tunable over a 120 nm range, and both the frequency and intensity can be modulated at up to 10 MHz by modulating the diode current. These features also make it suitable for other emerging applications in the 2 μm wavelength region including gas sensing, optical communications and LIDAR.
Mechanical ventilation for respiratory failure due to COVID-19 is associated with significant morbidity and mortality. Veno-venous extracorporeal membrane oxygenation (ECMO) is an attractive ...management option. This study sought to determine the effect of ECMO on hospital mortality and discharge condition in this population. We conducted a retrospective multicenter study to emulate a pragmatic targeted trial comparing ECMO to mechanical ventilation without ECMO for severe COVID-19. Data were gathered from a large hospital network database in the US. Adults admitted with COVID-19 were included if they were managed with ECMO or mechanical ventilation for severe hypoxemia and excluded if they had significant comorbidities or lacked functional independence on admission. The groups underwent coarsened exact matching on multiple clinical variables. The primary outcome was adjusted in-hospital mortality; secondary outcomes included ventilator days, intensive care days, and discharge destination. A total of 278 ECMO patients were matched to 2,054 comparison patients. Adjusted in-hospital mortality was significantly less in the ECMO group (38.8% vs. 60.1%, p < 0.001). Extracorporeal membrane oxygenation was associated with higher rates of liberation from mechanical ventilation, intensive care discharge, and favorable discharge destination. These findings support the use of ECMO for well-selected patients with severe acute respiratory failure due to COVID-19.
Differential equations posed over immersed manifolds are of particular importance in studying geophysical flows; for instance, ocean and atmosphere simulations crucially rely on the capability to ...solve equations over the sphere. This paper presents the extension of the FEniCS software components to the automated solution of finite element formulations of differential equations defined over general, immersed manifolds. We describe the implementation and, in particular detail, how the required extensions essentially reduce to the extension of the FEniCS form compiler to cover this case. The resulting implementation has all the properties of the FEniCS pipeline and we demonstrate its flexibility by an extensive range of numerical examples covering a number of geophysical benchmark examples and test cases. The results are all in agreement with the expected values. The description here relates to DOLFIN/FEniCS 1.2.
To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD).
Patients with severe AD (Mini-Mental State Examination MMSE scores 1 to 12 and Functional Assessment Staging FAST ...scores > or =6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving > or =1 dose of donepezil or placebo.
Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD.
Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.
The efficacy and safety of retreatment with varenicline in smokers attempting to quit were evaluated in this randomized, double‐blind, placebo‐controlled, multicenter trial (Australia, Belgium, ...Canada, the Czech Republic, France, Germany, the United Kingdom, and the United States). Participants were generally healthy adult smokers (≥10 cigarettes/day) with ≥1 prior quit attempt (≥2 weeks) using varenicline and no quit attempts in ≤3 months; they were randomly assigned (1:1) to 12 weeks' varenicline (n = 251) or placebo (n = 247) treatment, with individual counseling, plus 40 weeks' nontreatment follow‐up. The primary efficacy end point was the carbon monoxide–confirmed (≤10 ppm) continuous abstinence rate for weeks 9–12, which was 45.0% (varenicline; n = 249) vs. 11.8% (placebo; n = 245; odds ratio: 7.08; 95% confidence interval: 4.34, 11.55; P < 0.0001). Common varenicline group adverse events were nausea, abnormal dreams, and headache, with no reported suicidal behavior. Varenicline is efficacious and well tolerated in smokers who have previously taken it. Abstinence rates are comparable with rates reported for varenicline‐naive smokers.
Clinical Pharmacology & Therapeutics (2014); 96 3, 390–396. advance online publication 09 July 2014. doi:10.1038/clpt.2014.124
Eastern gray squirrels use three acoustically distinct vocalizations, namely kuks, quaas and moans, in their alarm calling bouts. Although moans are highly specific to aerial threats, kuks and quaas ...show no clear association with either terrestrial or aerial predator type when simply examining their presence or absence in an entire bout of vocal signaling. Here we examine the relationship between alarm call composition (the presence and rate of kuks, quaas and moans) and the type of stimulus eliciting the alarm call (aerial or terrestrial). When the first 30 sec or second 30 sec of calling is examined, the presence of kuks, quaas (only used in the second 30-sec period), and moans are all associated with stimulus type. Kuks and quaas are usually used in response to terrestrial stimuli and moans are used exclusively in response to aerial stimuli. The relationship between call composition and stimulus is even stronger when considering the rate of calls. In the first 60 sec of calling, all three vocalizations differ in rate depending on threat type, with more kuks and more quaas elicited by terrestrial than aerial stimuli, while moans are not produced at all with terrestrial stimuli. Overall rates of calling, combining all three vocalization types, also differed by stimulus type. The median number of vocalizations in the first 60 sec of calling bouts elicited by terrestrial threats was nearly 3 times greater than in calling bouts elicited by aerial threats. The alarm calls of gray squirrels are predator-specific, containing significant information on whether a threat is aerial or terrestrial. Further, the rate of each vocalization type in the initial 60 sec of calling bouts provides more information than does only the presence or absence of each vocalization type.
Squeezed light has become a standard technique to enhance the sensitivity of gravitational wave detectors. Both optical losses and phase noise in the squeezed path can degrade the achievable ...improvements. Phase noise can be mitigated by having a high bandwidth servo to stabilize the squeezer phase to the light from the interferometer. In advanced LIGO, this control loop bandwidth is limited by the 4 km arm cavity free spectral range to about ∼15 kHz. Future generation gravitational-wave detectors are designed to employ much longer arm cavities. For cosmic explorer 1, a 40 km arm length will limit the bandwidth to ∼1.5 kHz. We propose an alternative controls scheme that will increase the overall phase noise suppression by using the in-vacuum filter cavity as a reference for stabilizing the laser frequency of the squeezed light source. This will allow for rms phase noise of less than a milliradian-a negligible level for all future generations of gravitational-wave detectors 2.
PDF
