Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia.

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL. METHODS: Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living. RESULTS: Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke. CONCLUSIONS: The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL.Stroke Association (Grant ID: TSA2008/10), British Heart Foundation (Grant ID: PG/13/30/30005), Stroke Association/British Heart Foundation (Grant ID: TSA BHF 2010/01), Agency for Science, Technology and Research, Singapore, National Institute for Health Research (Senior Investigator award), Cambridge University Hospital Comprehensive National Institute for Health Research Biomedical Research UnitThis is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1161/STROKEAHA.116.01376

Encephalopathy in a Large Cohort of British Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients.

Background and Purpose- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke usually presenting with migraine with aura, lacunar infarcts, and cognitive impairment. Acute encephalopathy is a less recognized presentation of the disease. Methods- Data collected prospectively from 340 consecutively recruited symptomatic patients with diagnosis of CADASIL seen in a British National CADASIL clinic was retrospectively reviewed and original clinical records and imaging obtained. An encephalopathic event was defined as an acute event of an altered state of consciousness in a patient with CADASIL, manifesting with signs of brain dysfunction, which warranted hospital admission in the absence of any other cause. Clinical characteristics, risk factors, and outcome of encephalopathic presentations were studied. Results- A total of 35 of 340 (10.3%) participants had a history of 50 encephalopathic events which was the first hospital presentation of CADASIL in 33 (94.3%) patients. Most commonly reported features during episodes were visual hallucinations (44%), seizures (22%), and focal neurological deficits (60%).Complete recovery within 3 months was reported in 48(96%) episodes. In 62% of episodes, there was a history of migraine or migraine aura directly preceding the encephalopathy. In 2 out of 15 cases where magnetic resonance imaging during episodes was available, unilateral focal cortical swelling was seen. A past history of migraine was independently associated with encephalopathy (odds ratio=12.3 [95% CI, 1.6-93.7]; P=0.015). Conclusions- In up to 10% of CADASIL patients, a reversible encephalopathy is the first presentation leading to diagnosis. The strong association with migraine suggests a shared pathogenesis. Focal cortical swelling may be seen on magnetic resonance imaging during the acute episode

How much is enough? Minimal responses of water quality and stream biota to partial retrofit stormwater management in a suburban neighborhood

Decentralized stormwater management approaches (e.g., biofiltration swales, pervious pavement, green roofs, rain gardens) that capture, detain, infiltrate, and filter runoff are now commonly used to minimize the impacts of stormwater runoff from impervious surfaces on aquatic ecosystems. However, there is little research on the effectiveness of retrofit, parcel-scale stormwater management practices for improving downstream aquatic ecosystem health. A reverse auction was used to encourage homeowners to mitigate stormwater on their property within the suburban, 1.8 km2 Shepherd Creek catchment in Cincinnati, Ohio (USA). In 2007–2008, 165 rain barrels and 81 rain gardens were installed on 30% of the properties in four experimental (treatment) subcatchments, and two additional subcatchments were maintained as controls. At the base of the subcatchments, we sampled monthly baseflow water quality, and seasonal (5×/year) physical habitat, periphyton assemblages, and macroinvertebrate assemblages in the streams for the three years before and after treatment implementation. Given the minor reductions in directly connected impervious area from the rain barrel installations (11.6% to 10.4% in the most impaired subcatchment) and high total impervious levels (13.1% to 19.9% in experimental subcatchments), we expected minor or no responses of water quality and biota to stormwater management. There were trends of increased conductivity, iron, and sulfate for control sites, but no such contemporaneous trends for experimental sites. The minor effects of treatment on streamflow volume and water quality did not translate into changes in biotic health, and the few periphyton and macroinvertebrate responses could be explained by factors not associated with the treatment (e.g., vegetation clearing, drought conditions). Improvement of overall stream health is unlikely without additional treatment of major impervious surfaces (including roads, apartment buildings, and parking lots). Further research is needed to define the minimum effect threshold and restoration trajectories for retrofitting catchments to improve the health of stream ecosystems

3D Environment Modeling for Falsification and Beyond with Scenic 3.0

We present a major new version of Scenic, a probabilistic programming language for writing formal models of the environments of cyber-physical systems. Scenic has been successfully used for the design and analysis of CPS in a variety of domains, but earlier versions are limited to environments which are essentially two-dimensional. In this paper, we extend Scenic with native support for 3D geometry, introducing new syntax which provides expressive ways to describe 3D configurations while preserving the simplicity and readability of the language. We replace Scenic's simplistic representation of objects as boxes with precise modeling of complex shapes, including a ray tracing-based visibility system that accounts for object occlusion. We also extend the language to support arbitrary temporal requirements expressed in LTL, and build an extensible Scenic parser generated from a formal grammar of the language. Finally, we illustrate the new application domains these features enable with case studies that would have been impossible to accurately model in Scenic 2.Comment: 13 pages, 6 figures. Full version of a CAV 2023 tool paper, to appear in the Springer Lecture Notes in Computer Science serie

Strong surface termination dependence of the electronic structure of polar superconductor LaFeAsO revealed by nano-ARPES

LCR acknowledges funding from the Royal Commission for the Exhibition of 1851. The work at IFW was supported by the Deutsche Forschungsgemeinschaft (DFG) through the Priority Program SPP1458. SA thanks the DFG for funding (AS 523∖4-1 & 523∖3-1).The electronic structures of the iron-based superconductors have been intensively studied by using angle-resolved photoemission spectroscopy (ARPES). A considerable amount of research has been focused on the LaFeAsO family, showing the highest transition temperatures, where previous ARPES studies have found much larger Fermi surfaces than bulk theoretical calculations would predict. The discrepancy has been attributed to the presence of termination-dependent surface states. Here, using photoemission spectroscopy with a sub-micron focused beam spot (nano-ARPES) we have successfully measured the electronic structures of both the LaO and FeAs terminations in LaFeAsO. Our data reveal very different band dispersions and core-level spectra for different surface terminations, showing that previous macro-focus ARPES measurements were incomplete. Our results give direct evidence for the surface-driven electronic structure reconstruction in LaFeAsO, including formation of the termination-dependent surface states at the Fermi level. This experimental technique, which we have shown to be very powerful when applied to this prototypical compound, can now be used to study various materials with different surface terminations.Publisher PDFPeer reviewe

Simulation-based mastery learning compared to standard education for discussing diagnostic uncertainty with patients in the emergency department: a randomized controlled trial.

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications. METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to teach communication skills using simulation-based mastery learning (SBML). Resident emergency physicians from two training programs will be randomly assigned to immediate or delayed receipt of the two-part UCEM intervention after completing a baseline standardized patient encounter. The two UCEM components are: 1) a web-based interactive module, and 2) a smart-phone-based game. Both formats teach and reinforce communication skills for patient cases involving diagnostic uncertainty. Following baseline testing, participants in the immediate intervention arm will complete a remote deliberate practice session via a video platform and subsequently return for a second study visit to assess if they have achieved mastery. Participants in the delayed intervention arm will receive access to UCEM and remote deliberate practice after the second study visit. The primary outcome of interest is the proportion of residents in the immediate intervention arm who achieve mastery at the second study visit. DISCUSSION: Patients\u27 understanding of the care they received has implications for care quality, safety, and patient satisfaction, especially when they are discharged without a definitive diagnosis. Developing a patient-centered diagnostic uncertainty communication strategy will improve safety of acute care discharges. Although use of SBML is a resource intensive educational approach, this trial has been deliberately designed to have a low-resource, scalable intervention that would allow for widespread dissemination and uptake. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT04021771). Registration date: July 16, 2019

Emergent magnetism at transition-metal–nanocarbon interfaces

Charge transfer at metallo–molecular interfaces may be used to design multifunctional hybrids with an emergent magnetization that may offer an eco-friendly and tunable alternative to conventional magnets and devices. Here, we investigate the origin of the magnetism arising at these interfaces by using different techniques to probe 3d and 5d metal films such as Sc, Mn, Cu, and Pt in contact with fullerenes and rf-sputtered carbon layers. These systems exhibit small anisotropy and coercivity together with a high Curie point. Low-energy muon spin spectroscopy in Cu and Sc–C60 multilayers show a quick spin depolarization and oscillations attributed to nonuniform local magnetic fields close to the metallo–carbon interface. The hybridization state of the carbon layers plays a crucial role, and we observe an increased magnetization as sp3 orbitals are annealed into sp2−π graphitic states in sputtered carbon/copper multilayers. X-ray magnetic circular dichroism (XMCD) measurements at the carbon K edge of C60 layers in contact with Sc films show spin polarization in the lowest unoccupied molecular orbital (LUMO) and higher π*-molecular levels, whereas the dichroism in the σ*-resonances is small or nonexistent. These results support the idea of an interaction mediated via charge transfer from the metal and dz–π hybridization. Thin-film carbon-based magnets may allow for the manipulation of spin ordering at metallic surfaces using electrooptical signals, with potential applications in computing, sensors, and other multifunctional magnetic devices

When Is Visual Information Used to Control Locomotion When Descending a Kerb?

YesBackground: Descending kerbs during locomotion involves the regulation of appropriate foot placement before the kerb-edge and foot clearance over it. It also involves the modulation of gait output to ensure the body-mass is safely and smoothly lowered to the new level. Previous research has shown that vision is used in such adaptive gait tasks for feedforward planning, with vision from the lower visual field (lvf) used for online updating. The present study determined when lvf information is used to control/update locomotion when stepping from a kerb. Methodology/Principal Findings: 12 young adults stepped down a kerb during ongoing gait. Force sensitive resistors (attached to participants' feet) interfaced with an high-speed PDLC 'smart glass' sheet, allowed the lvf to be unpredictably occluded at either heel-contact of the penultimate or final step before the kerb-edge up to contact with the lower level. Analysis focussed on determining changes in foot placement distance before the kerb-edge, clearance over it, and in kinematic measures of the step down. Lvf occlusion from the instant of final step contact had no significant effect on any dependant variable (p>0.09). Occlusion of the lvf from the instant of penultimate step contact had a significant effect on foot clearance and on several kinematic measures, with findings consistent with participants becoming uncertain regarding relative horizontal location of the kerb-edge. Conclusion/Significance: These findings suggest concurrent feedback of the lower limb, kerb-edge, and/or floor area immediately in front/below the kerb is not used when stepping from a kerb during ongoing gait. Instead heel-clearance and pre-landing-kinematic parameters are determined/planned using lvf information acquired in the penultimate step during the approach to the kerb-edge, with information related to foot placement before the kerb-edge being the most salient

The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia

How the 22q11.2 deletion predisposes to psychiatric disease is unclear. Here, the authors examine living human neuronal cells and show that 22q11.2 regulates the expression of genes linked to autism during early development, and genes linked to schizophrenia and synaptic biology in neurons. It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.Peer reviewe