BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date. CASE PRESENTATION: A 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment. CONCLUSION: This case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.

We propose a short period undulator which is based on the alternating electromagnetic field pattern of THz-driven surface plasmons in a thin conductive layer on a dielectric grating. An approximate analytical model allows to assess the key performance parameters of the undulator and to estimate the emitted radiation spectrum. The specific example of a graphene based undulator is simulated in detail. For a moderate electron beam energy of 100 MeV and a bunch charge of 0.5 pC the 40 mm long undulator is shown to emit narrow band 1 keV X-ray pulses with a peak brightness of approximately 1016 photons/(s mrad2 mm2 0.1% BW). It therefore has potential for a compact and low cost X-ray source.

BACKGROUND: Bloodborne pathogens pose a major safety risk in transfusion medicine. To mitigate the risk of bacterial contamination in platelet units, FDA issues updated guidance materials on various bacterial risk control strategies (BRCS). This analysis presents results of a budget impact model updated to include 5- and 7-day pathogen reduced (PR) and large volumed delayed sampling (LVDS) BRCS. STUDY DESIGN AND METHODS: Model base-case parameter inputs were based on scientific literature, a survey distributed to 27 US hospitals, and transfusion experts opinion. The outputs include hospital budget and shelf-life impacts for 5- and 7-day LVDS, and 5- and 7-day PR units under three different scenarios: (1) 100% LVDS, (2) 100% PR, and (3) mix of 50% LVDS - and 50% PR. RESULTS: Total annual costs from the hospital perspective were highest for 100% LVDS platelets (US$2.325M) and lowest for 100% PR-7 units (US$2.170M). Net budget impact after offsetting annual costs by outpatient reimbursements was 5.5% lower for 5-day PR platelets as compared to 5-day LVDS (US$1.663 vs. US$1.760M). A mix of 7-day LVDS and 5-day PR platelets had net annual costs that were 1.3% lower than for 100% 7-day LVDS, but 1.3% higher than for 100% 5-day PR. 7-day PR platelets had the longest shelf life (4.63 days), while 5-day LVDS had the shortest (2.00 days). DISCUSSION: The model identifies opportunities to minimize transfusion center costs for 5- and 7-day platelets. Budget impact models such as this are important for understanding the financial implications of evolving FDA guidance and new platelet technologies.

Introduction

Subjective cognitive decline (SCD) is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Although sleep has been shown to be altered in MCI and AD, little is known about sleep in SCD.

Methods

Seventy cognitively normal community-dwelling participants were classified as SCD (32) or controls (38) using the Subjective Cognitive Decline Questionnaire. Sleep was assessed using actigraphy and diaries. FreeSurfer was used for performing medial temporal lobes (MTLs) and brain cortical parcellation of 3T magnetic resonance images. Multiple regression models were used to assess the presence of sleep, MTL, or regional cortical differences between groups.

Results

Objective sleep was disrupted in SCD participants, which showed increased nighttime wakefulness and reduced sleep efficiency. No group differences emerged in subjective sleep or magnetic resonance imaging outcomes.

Discussion

Objective sleep resulted disrupted in community-dwelling SCD, without any subjective sleep or cortical change. Sleep assessment/intervention in SCD might help prevent/delay AD onset.

INTRODUCTION:Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). MATERIAL AND METHODS:A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. RESULTS:The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. CONCLUSIONS:Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk.

Zinc (Zn²⁺) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn²⁺ levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn²⁺ affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn²⁺ levels, we employed the Zn²⁺ (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signaling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn²⁺ was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo. Our study highlights the importance of choosing "when", "where", and "how much" in the modulation of brain Zn²⁺ levels. Our findings confirm the importance of targeting Zn²⁺ as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn²⁺ availability upon the early stages of development.

The prediction of material properties through electronic-structure simulations based on density-functional theory has become routinely common, thanks, in part, to the steady increase in the number and robustness of available simulation packages. This plurality of codes and methods aiming to solve similar problems is both a boon and a burden. While providing great opportunities for cross-verification, these packages adopt different methods, algorithms, and paradigms, making it challenging to choose, master, and efficiently use any one for a given task. Leveraging recent advances in managing reproducible scientific workflows, we demonstrate how developing common interfaces for workflows that automatically compute material properties can tackle the challenge mentioned above, greatly simplifying interoperability and cross-verification. We introduce design rules for reproducible and reusable code-agnostic workflow interfaces to compute well-defined material properties, which we implement for eleven different quantum engines and use to compute three different material properties. Each implementation encodes carefully selected simulation parameters and workflow logic, making the implementer's expertise of the quantum engine directly available to non-experts. Full provenance and reproducibility of the workflows is guaranteed through the use of the AiiDA infrastructure. All workflows are made available as open-source and come pre-installed with the Quantum Mobile virtual machine, making their use straightforward.

Materials Cloud is a platform designed to enable open and seamless sharing of resources for computational science, driven by applications in materials modelling. It hosts (1) archival and dissemination services for raw and curated data, together with their provenance graph, (2) modelling services and virtual machines, (3) tools for data analytics, and pre-/post-processing, and (4) educational materials. Data is citable and archived persistently, providing a comprehensive embodiment of entire simulation pipelines (calculations performed, codes used, data generated) in the form of graphs that allow retracing and reproducing any computed result. When an AiiDA database is shared on Materials Cloud, peers can browse the interconnected record of simulations, download individual files or the full database, and start their research from the results of the original authors. The infrastructure is agnostic to the specific simulation codes used and can support diverse applications in computational science that transcend its initial materials domain.

Objective

To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB).

Methods

Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales.

Results

A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72).

Conclusions

OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.

The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification.