Treatment-resistant major depression: Rationale for NMDA receptors as targets and nitrous oxide as therapy

Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant

Electron correlations in the antiproton energy-loss distribution in He

We present ab initio calculations of the electronic differential energy-transfer cross sections for antiprotons with energies between 3 keV and 1 MeV interacting with helium. By comparison with simulations employing the mean-field description based on the single-active electron approximation we are able to identify electron correlation effects in the stopping and straggling cross sections. Most remarkably, we find that straggling exceeds the celebrated Bohr straggling limit when correlated shake-up processes are included.The present paper was supported by Grants No. FWF-SFB049 (Nextlite), No. FWF-SFB041 (VICOM), No. WWTF MA14-002, Doctoral College Grant No. FWF-W1243 (Solids4Function), by the National Research, Development and Innovation Office (NKFIH) Grant No. KH 126886, and by the high performance computing resources of the Babeş-Bolyai University. J.F. acknowledges funding from the European Research Council under Grant No. ERC-2016-STG-714870 and by the Ministerio de Economía y Competitividad (Spain) through a Ramón y Cajal grant. X.- M.T. was supported by a Grants-in-Aid for Scientific Research (Grant No. JP16K05495) from the Japan Society for the Promotion of Scienc

Diagnosis of Alzheimer's Disease Based on Disease-Specific Autoantibody Profiles in Human Sera

After decades of Alzheimer's disease (AD) research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC) groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease

Electron correlations in the antiproton energy-loss distribution in He

We present ab initio calculations of the electronic differential energy-transfer cross sections for antiprotons with energies between 3 keV and 1 MeV interacting with helium. By comparison with simulations employing the mean-field description based on the single-active electron approximation we are able to identify electron correlation effects in the stopping and straggling cross sections. Most remarkably, we find that straggling exceeds the celebrated Bohr straggling limit when correlated shake-up processes are included

Evidence-Based Cognitive Rehabilitation: Systematic Review of the Literature From 2009 Through 2014

Objective To conduct an updated, systematic review of the clinical literature, classify studies based on the strength of research design, and derive consensual, evidence-based clinical recommendations for cognitive rehabilitation of people with TBI or stroke. Data Sources Online Pubmed and print journal searches identified citations for 250 articles published from 2009 through 2014. Study Selection 186 articles were selected for inclusion after initial screening. 50 articles were initially excluded (24 healthy, pediatric or other neurologic diagnoses, 10 non-cognitive interventions, 13 descriptive protocols or studies, 3 non-treatment studies). 15 articles were excluded after complete review (1 other neurologic diagnosis, 2 non-treatment studies, 1 qualitative study, 4 descriptive papers, 7 secondary analyses). 121 studies were fully reviewed. Data Extraction Articles were reviewed by CRTF members according to specific criteria for study design and quality, and classified as providing Class I, Class II, or Class III evidence. Articles were assigned to 1 of 6 possible categories (based on interventions for attention, vision and neglect, language and communication skills, memory, executive function, or comprehensive-integrated interventions). Data Synthesis Of 121 studies, 41 were rated as Class I, 3 as Class Ia, 14 as Class II, and 63 as Class III. Recommendations were derived by CRTF consensus from the relative strengths of the evidence, based on the decision rules applied in prior reviews. Conclusions CRTF has now evaluated 491 papers (109 Class I or Ia, 68 Class II, and 314 Class III) and makes 29 recommendations for evidence-based practice of cognitive rehabilitation (9 Practice Standards, 9 Practice Guidelines and 11 Practice Options). Evidence supports Practice Standards for attention deficits after TBI or stroke; visual scanning for neglect after right hemisphere stroke; compensatory strategies for mild memory deficits; language deficits after left hemisphere stroke; social communication deficits after TBI; metacognitive strategy training for deficits in executive functioning; and comprehensive-holistic neuropsychological rehabilitation to reduce cognitive and functional disability after TBI or stroke

Electron correlation in two-photon double ionization of helium from attosecond to FEL pulses

We investigate the role of electron correlation in the two-photon double ionization of helium for ultrashort XUV pulses with durations ranging from a hundred attoseconds to a few femtoseconds. We perform time-dependent ab initio calculations for pulses with mean frequencies in the so-called "sequential" regime (photon energy above 54.4 eV). Electron correlation induced by the time correlation between emission events manifests itself in the angular distribution of the ejected electrons, which strongly depends on the energy sharing between them. We show that for ultrashort pulses two-photon double ionization probabilities scale non-uniformly with pulse duration depending on the energy sharing between the electrons. Most interestingly we find evidence for an interference between direct ("nonsequential") and indirect ("sequential") double photo-ionization with intermediate shake-up states, the strength of which is controlled by the pulse duration. This observation may provide a route toward measuring the pulse duration of FEL pulses.Comment: 9 pages, 6 figure

Proving Ground Confluence of Equational Specifications Modulo Axioms

Terminating functional programs should be deterministic, i.e., should evaluate to a unique result, regardless of the evaluation order. For equational functional programs such determinism is exactly captured by the ground confluence property. For terminating equations this is equivalent to ground local confluence, which follows from local confluence. Checking local confluence by computing critical pairs is the standard way to check ground confluence. The problem is that some perfectly reasonable equational programs are not locally confluent and it can be very hard or even impossible to make them so by adding more equations. We propose a three-step strategy to prove that an equational program as is is ground confluent: First: apply the strategy proposed in [8] to use non-joinable critical pairs as completion hints to either achieve local confluence or reduce the number of critical pairs. Second: use the inductive inference system proposed in this paper to prove the remaining critical pairs ground joinable. Third: to show ground confluence of the original specification, prove also ground joinable the equations added. These methods apply to order-sorted and possibly conditional equational programs modulo axioms such as, e.g., Maude functional modules.This work has been partially supported by NRL under contract number N00173-17-1-G002.Ope

Towards a novel biologically-inspired cloud elasticity framework

With the widespread use of the Internet, the popularity of web applications has significantly increased. Such applications are subject to unpredictable workload conditions that vary from time to time. For example, an e-commerce website may face higher workloads than normal during festivals or promotional schemes. Such applications are critical and performance related issues, or service disruption can result in financial losses. Cloud computing with its attractive feature of dynamic resource provisioning (elasticity) is a perfect match to host such applications. The rapid growth in the usage of cloud computing model, as well as the rise in complexity of the web applications poses new challenges regarding the effective monitoring and management of the underlying cloud computational resources. This thesis investigates the state-of-the-art elastic methods including the models and techniques for the dynamic management and provisioning of cloud resources from a service provider perspective. An elastic controller is responsible to determine the optimal number of cloud resources, required at a particular time to achieve the desired performance demands. Researchers and practitioners have proposed many elastic controllers using versatile techniques ranging from simple if-then-else based rules to sophisticated optimisation, control theory and machine learning based methods. However, despite an extensive range of existing elasticity research, the aim of implementing an efficient scaling technique that satisfies the actual demands is still a challenge to achieve. There exist many issues that have not received much attention from a holistic point of view. Some of these issues include: 1) the lack of adaptability and static scaling behaviour whilst considering completely fixed approaches; 2) the burden of additional computational overhead, the inability to cope with the sudden changes in the workload behaviour and the preference of adaptability over reliability at runtime whilst considering the fully dynamic approaches; and 3) the lack of considering uncertainty aspects while designing auto-scaling solutions. This thesis seeks solutions to address these issues altogether using an integrated approach. Moreover, this thesis aims at the provision of qualitative elasticity rules. This thesis proposes a novel biologically-inspired switched feedback control methodology to address the horizontal elasticity problem. The switched methodology utilises multiple controllers simultaneously, whereas the selection of a suitable controller is realised using an intelligent switching mechanism. Each controller itself depicts a different elasticity policy that can be designed using the principles of fixed gain feedback controller approach. The switching mechanism is implemented using a fuzzy system that determines a suitable controller/- policy at runtime based on the current behaviour of the system. Furthermore, to improve the possibility of bumpless transitions and to avoid the oscillatory behaviour, which is a problem commonly associated with switching based control methodologies, this thesis proposes an alternative soft switching approach. This soft switching approach incorporates a biologically-inspired Basal Ganglia based computational model of action selection. In addition, this thesis formulates the problem of designing the membership functions of the switching mechanism as a multi-objective optimisation problem. The key purpose behind this formulation is to obtain the near optimal (or to fine tune) parameter settings for the membership functions of the fuzzy control system in the absence of domain experts’ knowledge. This problem is addressed by using two different techniques including the commonly used Genetic Algorithm and an alternative less known economic approach called the Taguchi method. Lastly, we identify seven different kinds of real workload patterns, each of which reflects a different set of applications. Six real and one synthetic HTTP traces, one for each pattern, are further identified and utilised to evaluate the performance of the proposed methods against the state-of-the-art approaches

The coronary CT angiography vision protocol : a prospective observational imaging cohort study in patients undergoing non-cardiac surgery

INTRODUCTION: At present, physicians have a limited ability to predict major cardiovascular complications after non-cardiac surgery and little is known about the anatomy of coronary arteries associated with perioperative myocardial infarction. We have initiated the Coronary CT Angiography (CTA) VISION Study to (1) establish the predictive value of coronary CTA for perioperative myocardial infarction and death and (2) describe the coronary anatomy of patients that have a perioperative myocardial infarction. METHODS AND ANALYSIS: The Coronary CTA VISION Study is prospective observational study. Preoperative coronary CTA will be performed in 1000–1500 patients with a history of vascular disease or at least three cardiovascular risk factors who are undergoing major elective non-cardiac surgery. Serial troponin will be measured 6–12 h after surgery and daily for the first 3 days after surgery. Major vascular outcomes at 30 days and 1 year after surgery will be independently adjudicated. ETHICS AND DISSEMINATION: Coronary CTA results in a measurable radiation exposure that is similar to a nuclear perfusion scan (10–12 mSV). Treating physicians will be blinded to the CTA results until 30 days after surgery in order to provide the most unbiased assessment of its prognostic capabilities. The only exception will be the presence of a left main stenosis >50%. This approach is supported by best available current evidence that, excluding left main disease, prophylatic revascularisation prior to non-cardiac surgery does not improve outcomes. An external safety and monitoring committee is overseeing the study and will review outcome data at regular intervals. Publications describing the results of the study will be submitted to major peer-reviewed journals and presented at international medical conferences