330 research outputs found
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
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