Exposure to anesthetics during synaptogenesis results in apoptosis and subsequent cognitive dysfunction in adulthood. Probrain-derived neurotrophic factor (proBDNF) is involved in synaptogenesis and ...can induce neuronal apoptosis via p75 neurotrophic receptors (p75). proBDNF is cleaved into mature BDNF (mBDNF) by plasmin, a protease converted from plasminogen by tissue plasminogen activator (tPA) that is released with neuronal activity; mBDNF supports survival and stabilizes synapses through tropomyosin receptor kinase B. The authors hypothesized that anesthetics suppress tPA release from neurons, enhance p75 signaling, and reduce synapses, resulting in apoptosis.
Primary neurons (DIV5) and postnatal day 5-7 (PND5-7) mice were exposed to isoflurane (1.4%, 4 h) in 5% CO2, 95% air. Apoptosis was assessed by cleaved caspase-3 (Cl-Csp3) immunoblot and immunofluorescence microscopy. Dendritic spine changes were evaluated with the neuronal spine marker, drebrin. Changes in synapses in PND5-7 mouse hippocampi were assessed by electron microscopy. Primary neurons were exposed to tPA, plasmin, or pharmacologic inhibitors of p75 (Fc-p75 or TAT-Pep5) 15 min before isoflurane. TAT-Pep5 was administered by intraperitoneal injection to PND5-7 mice 15 min before isoflurane.
Exposure of neurons in vitro (DIV5) to isoflurane decreased tPA in the culture medium, reduced drebrin expression (marker of dendritic filopodial spines), and enhanced Cl-Csp3. tPA, plasmin, or TAT-Pep5 stabilized dendritic filopodial spines and decreased Cl-Csp3 in neurons. TAT-Pep5 blocked isoflurane-mediated increase in Cl-Csp3 and reduced synapses in PND5-7 mouse hippocampi.
tPA, plasmin, or p75 inhibition blocked isoflurane-mediated reduction in dendritic filopodial spines and neuronal apoptosis in vitro. Isoflurane reduced synapses and enhanced Cl-Csp3 in the hippocampus of PND5-7 mice, the latter effect being mitigated by p75 inhibition in vivo. These data support the hypothesis that isoflurane neurotoxicity in the developing rodent brain is mediated by reduced synaptic tPA release and enhanced proBDNF/p75-mediated apoptosis.
The family of layered carbides and nitrides known as MAX phase ceramics combine many attractive properties of both ceramics and metals due to their nanolaminate crystal structure and are promising ...potential candidates for application in future nuclear reactors. This investigation examines the effects of energetic heavy ion (5.8 MeV Ni) irradiations on polycrystalline samples of Ti3SiC2, Ti3AlC2, and Ti2AlC. The irradiation conditions consisted of midrange ion doses between 10 and 30 displacements per atom at temperatures of 400 and 700 °C, conditions relevant to application in future nuclear reactors and a relatively un-explored regime for this new class of materials. Following irradiation, a comprehensive analysis of radiation response properties was compiled using grazing incidence X-ray diffraction (XRD), nanoindentation, scanning electron microcopy (SEM), and transmission electron microscopy (TEM). In all cases, XRD and TEM analyses confirm the materials remain fully crystalline although the intense atomic collisions induce significant damage and disorder into the layered crystalline lattice. X-ray diffraction and nanoindentation show this damage is manifest in anisotropic swelling and hardening at all conditions and in all materials, with the aluminum based MAX phase exhibiting significantly more damage than their silicon counterpart. In all three materials there is little damage dependence on dose, suggesting saturation of radiation damage at levels below 10 displacements per atom, and significantly less retained damage at higher temperatures, suggesting radiation defect annealing. SEM surface analysis showed significant grain boundary cracking and loss of damage tolerance properties in the aluminum-based MAX phase irradiated at 400 °C, but not in the silicon counterpart. TEM analysis of select samples suggest that interstitials are highly mobile while vacancies are immobile and that all three materials are in the so-called point defect swelling regime between 400 and 700 °C. All results are consistent with previous work involving traditional and MAX phase ceramics. Results show the aluminum MAX phases are not fit for application near 400 °C and that the silicon MAX phase is more damage tolerant at 400–700 °C.
Aluminum MAX phases (Ti3AlC2,Ti2AlC) are not fit for application in irradiation environments near 400 °C due to anisotropic swelling that induces cracking, whereas the Ti3SiC2 MAX phase is overall more damage tolerant at 400–700 °C. Display omitted
A method for designing transformation electromagnetics devices using tensor impedance surfaces is presented. The method is first applied to idealized tensor impedance boundary conditions (TIBCs), and ...later to printed-circuit tensor impedance surfaces (PCTISs). A PCTIS is a practical realization of a TIBC. It consists of a tensor impedance sheet, which models a subwavelength patterned metallic cladding, over a grounded dielectric substrate. The method outlined in this paper allows anisotropic TIBCs and PCTISs to be designed that support tangential wave vector distributions and power flow directions specified by a coordinate transformation. As an example, beam-shifting devices are designed, using TIBCs and PCTISs, that allow a surface wave to be shifted laterally. The designs are verified with a commercial full-wave electromagnetic solver. This work opens new opportunities for the design and implementation of anisotropic and inhomogeneous printed-circuit or graphene-based surfaces that can guide or radiate electromagnetic fields.
Analysis of a printed-circuit tensor impedance surface (PCTIS) is presented. The surface consists of a periodic, subwavelength-patterned metallic cladding printed over a grounded dielectric ...substrate. First, the dispersion equation for an idealized tensor impedance boundary condition is derived by expressing the field in terms of TE and TM waves. A similar method is then used to find the dispersion equation of the PCTIS consisting of a tensor sheet impedance, which models the metallic cladding, over a grounded dielectric substrate. In addition, a method for extracting the tensor sheet impedance of a periodic, metallic cladding printed over a grounded dielectric substrate, is reported. It involves performing two normal-incidence scattering simulations using a full-wave electromagnetic solver. The method is strictly valid when the ground plane is sufficiently far from the metallic cladding to avoid evanescent-wave interactions. By combining the tensor sheet extraction method with the dispersion equation, the full dispersion characteristics of the PCTIS are analytically predicted in the homogenous limit. The results are verified through full-wave eigenmode simulations.
To date, research on demand side management has mostly focused on the determinants of electricity consumption and stated preference experiments to understand social acceptability. Further ...experimental research is needed to identify the determinants for demand response schemes. This paper contributes to addressing this gap by making use of data from a randomised control trial which contains 15 months of smart meter electricity data combined with household characteristics and differences in incentives to shift their electricity use between 11am and 3pm. Cluster analysis performed on electricity data identified three distinct electricity daily load profiles. Each cluster was then linked to household characteristics by means of a multinomial logistic regression to identify the determinants of the load curves' shapes. Findings show that occupancy presence at home, age and appliance ownership were strong predictors. Finally, this paper is among the first to provide experimental evidence on the determinants of load shifting. We find that households with head aged above 65, households who belong to the cluster exhibiting a load profile characterised by a relatively high peak at noon and a low peak in the evening, and those who received money incentives were more likely to shift electricity use towards middle of the day (11am-3pm).
•A cluster analysis on smart-meter data identifies typical load profiles.•Regression models are used to identify determinants of load profile and shifting.•Occupancy presence, number of wet appliances and age influence the load profile.•Financial incentives are more effective than information feedback for load shifting.•Occupancy availability during noon is a major factor enabling load shifting.
Noncontact biometrics such as face and iris have additional benefits over contact-based biometrics such as fingerprint and hand geometry. However, three important challenges need to be addressed in a ...noncontact biometrics-based authentication system: ability to handle unconstrained acquisition, robust and accurate matching, and privacy enhancement without compromising security. In this paper, we propose a unified framework based on random projections and sparse representations, that can simultaneously address all three issues mentioned above in relation to iris biometrics. Our proposed quality measure can handle segmentation errors and a wide variety of possible artifacts during iris acquisition. We demonstrate how the proposed approach can be easily extended to handle alignment variations and recognition from iris videos, resulting in a robust and accurate system. The proposed approach includes enhancements to privacy and security by providing ways to create cancelable iris templates. Results on public data sets show significant benefits of the proposed approach.
Adversarially Robust One-Class Novelty Detection Lo, Shao-Yuan; Oza, Poojan; Patel, Vishal M.
IEEE transactions on pattern analysis and machine intelligence,
04/2023, Letnik:
45, Številka:
4
Journal Article
Recenzirano
Odprti dostop
One-class novelty detectors are trained with examples of a particular class and are tasked with identifying whether a query example belongs to the same known class. Most recent advances adopt a deep ...auto-encoder style architecture to compute novelty scores for detecting novel class data. Deep networks have shown to be vulnerable to adversarial attacks, yet little focus is devoted to studying the adversarial robustness of deep novelty detectors. In this article, we first show that existing novelty detectors are susceptible to adversarial examples. We further demonstrate that commonly-used defense approaches for classification tasks have limited effectiveness in one-class novelty detection. Hence, we need a defense specifically designed for novelty detection. To this end, we propose a defense strategy that manipulates the latent space of novelty detectors to improve the robustness against adversarial examples. The proposed method, referred to as Principal Latent Space (PrincipaLS), learns the incrementally-trained cascade principal components in the latent space to robustify novelty detectors. PrincipaLS can purify latent space against adversarial examples and constrain latent space to exclusively model the known class distribution. We conduct extensive experiments on eight attacks, five datasets and seven novelty detectors, showing that PrincipaLS consistently enhances the adversarial robustness of novelty detection models.
Clinical practice guideline (update): adult sinusitis Rosenfeld, Richard M; Piccirillo, Jay F; Chandrasekhar, Sujana S ...
Otolaryngology-head and neck surgery,
April 2015, Letnik:
152, Številka:
2 Suppl
Journal Article
Recenzirano
Odprti dostop
This update of a 2007 guideline from the American Academy of Otolaryngology--Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as ...symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS).
The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing adult rhinosinusitis and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy for adult rhinosinusitis, promote appropriate use of ancillary tests to confirm diagnosis and guide management, and promote judicious use of systemic and topical therapy, which includes radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia.
The update group made strong recommendations that clinicians (1) should distinguish presumed ABRS from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and noninfectious conditions and (2) should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. The update group made recommendations that clinicians (1) should either offer watchful waiting (without antibiotics) or prescribe initial antibiotic therapy for adults with uncomplicated ABRS; (2) should prescribe amoxicillin with or without clavulanate as first-line therapy for 5 to 10 days (if a decision is made to treat ABRS with an antibiotic); (3) should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens during the initial management; (4) should distinguish CRS and recurrent ARS from isolated episodes of ABRS and other causes of sinonasal symptoms; (5) should assess the patient with CRS or recurrent ARS for multiple chronic conditions that would modify management, such as asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia; (6) should confirm the presence or absence of nasal polyps in a patient with CRS; and (7) should recommend saline nasal irrigation, topical intranasal corticosteroids, or both for symptom relief of CRS. The update group stated as options that clinicians may (1) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation for symptomatic relief of viral rhinosinusitis; (2) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation) for symptomatic relief of ABRS; and (3) obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent ARS. The update group made recommendations that clinicians (1) should not obtain radiographic imaging for patients who meet diagnostic criteria for ARS, unless a complication or alternative diagnosis is suspected, and (2) should not prescribe topical or systemic antifungal therapy for patients with CRS.
In recent years, there has been an increased emphasis on the diagnosis and treatment of valvular heart disease and, in particular, aortic stenosis. This has been driven in part by the development of ...innovative therapeutic options and by an aging patient population. We hypothesized an increase in the number of hospitalizations and the economic burden associated with aortic valve disease (AVD). Using Nationwide Inpatient Sample from 2000 to 2012, AVD-related hospitalizations were identified using International Classification of Diseases, Ninth Revision, Clinical Modification , code 424.1, as the principal discharge diagnosis. Overall AVD hospitalizations increased by 59% from 2000 to 2012. This increase was most significant in patients >80 years and those with higher burden of co-morbidities. The most frequent coexisting conditions were hypertension, heart failure, renal failure, anemia, and diabetes. Overall inhospital mortality of patients hospitalized for AVD was 3.8%, which significantly decreased from 4.5% in 2000 to 3.5% in 2012 (p <0.001). The largest decrease in mortality was seen in the subgroup of patients who had heart failure (62% reduction), higher burden of co-morbidities (58% reduction), and who were >80 years (53% reduction). There was a substantial increase in the cost of hospitalization in the last decade from $31,909 to $38,172 (p <0.001). The total annual cost for AVD hospitalization in the United States increased from $1.3 billion in 2001 to $2.1 billion in 2011 and is expected to increase to nearly 3 billion by 2020. The last decade has witnessed a significant increase in hospitalizations for AVD in the United States. The associated decrease in inhospital mortality and increase in the cost of hospitalization have considerably increased the economic burden on the public health system.
Abstract This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and ...adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract.
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