scholarly journals Consciousness as a multidimensional phenomenon: implications for the assessment of disorders of consciousness

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Jasmine Walter
Keyword(s):  
Research Effort ◽  
Conscious Experience ◽  
Ground Truth ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Ethical Challenge ◽  
Ongoing Research ◽  
External Responsiveness ◽  
Conscious Level ◽  
Complex Forms

Abstract Disorders of consciousness (DoCs) pose a significant clinical and ethical challenge because they allow for complex forms of conscious experience in patients where intentional behaviour and communication are highly limited or non-existent. There is a pressing need for brain-based assessments that can precisely and accurately characterize the conscious state of individual DoC patients. There has been an ongoing research effort to develop neural measures of consciousness. However, these measures are challenging to validate not only due to our lack of ground truth about consciousness in many DoC patients but also because there is an open ontological question about consciousness. There is a growing, well-supported view that consciousness is a multidimensional phenomenon that cannot be fully described in terms of the theoretical construct of hierarchical, easily ordered conscious levels. The multidimensional view of consciousness challenges the utility of levels-based neural measures in the context of DoC assessment. To examine how these measures may map onto consciousness as a multidimensional phenomenon, this article will investigate a range of studies where they have been applied in states other than DoC and where more is known about conscious experience. This comparative evidence suggests that measures of conscious level are more sensitive to some dimensions of consciousness than others and cannot be assumed to provide a straightforward hierarchical characterization of conscious states. Elevated levels of brain complexity, for example, are associated with conscious states characterized by a high degree of sensory richness and minimal attentional constraints, but are suboptimal for goal-directed behaviour and external responsiveness. Overall, this comparative analysis indicates that there are currently limitations to the use of these measures as tools to evaluate consciousness as a multidimensional phenomenon and that the relationship between these neural signatures and phenomenology requires closer scrutiny.

scholarly journals Pain Perception in Disorder of Consciousness: A Scoping Review on Current Knowledge, Clinical Applications, and Future Perspective

2021 ◽  
Vol 11 (5) ◽  
pp. 665
Author(s):  
Rocco Salvatore Calabrò ◽  
Loris Pignolo ◽  
Claudia Müller-Eising ◽  
Antonino Naro
Keyword(s):  
Functional Connectivity ◽  
Scoping Review ◽  
Pain Perception ◽  
Current Knowledge ◽  
Conscious Experience ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Future Perspective ◽  
Disorder Of Consciousness ◽  
Minimally Conscious

Pain perception in individuals with prolonged disorders of consciousness (PDOC) is still a matter of debate. Advanced neuroimaging studies suggest some cortical activations even in patients with unresponsive wakefulness syndrome (UWS) compared to those with a minimally conscious state (MCS). Therefore, pain perception has to be considered even in individuals with UWS. However, advanced neuroimaging assessment can be challenging to conduct, and its findings are sometimes difficult to be interpreted. Conversely, multichannel electroencephalography (EEG) and laser-evoked potentials (LEPs) can be carried out quickly and are more adaptable to the clinical needs. In this scoping review, we dealt with the neurophysiological basis underpinning pain in PDOC, pointing out how pain perception assessment in these individuals might help in reducing the misdiagnosis rate. The available literature data suggest that patients with UWS show a more severe functional connectivity breakdown among the pain-related brain areas compared to individuals in MCS, pointing out that pain perception increases with the level of consciousness. However, there are noteworthy exceptions, because some UWS patients show pain-related cortical activations that partially overlap those observed in MCS individuals. This suggests that some patients with UWS may have residual brain functional connectivity supporting the somatosensory, affective, and cognitive aspects of pain processing (i.e., a conscious experience of the unpleasantness of pain), rather than only being able to show autonomic responses to potentially harmful stimuli. Therefore, the significance of the neurophysiological approach to pain perception in PDOC seems to be clear, and despite some methodological caveats (including intensity of stimulation, multimodal paradigms, and active vs. passive stimulation protocols), remain to be solved. To summarize, an accurate clinical and neurophysiological assessment should always be performed for a better understanding of pain perception neurophysiological underpinnings, a more precise differential diagnosis at the level of individual cases as well as group comparisons, and patient-tailored management.

scholarly journals Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 482
Author(s):  
Irene Paraboschi ◽  
Laura Privitera ◽  
Gabriela Kramer-Marek ◽  
John Anderson ◽  
Stefano Giuliani
Keyword(s):  
Research Effort ◽  
Treatment Strategies ◽  
Adverse Outcomes ◽  
Treatment Protocols ◽  
Ongoing Research ◽  
Hematopoietic Stem ◽  
Novel Treatments ◽  
Therapeutic Modalities ◽  
High Risk Disease ◽  
Novel Treatment Strategies

Neuroblastoma (NB) is the most common extracranial solid tumour in childhood, accounting for approximately 15% of all cancer-related deaths in the paediatric population1. It is characterised by heterogeneous clinical behaviour in neonates and often adverse outcomes in toddlers. The overall survival of children with high-risk disease is around 40–50% despite the aggressive treatment protocols consisting of intensive chemotherapy, surgery, radiation therapy and hematopoietic stem cell transplantation2,3. There is an ongoing research effort to increase NB’s cellular and molecular biology knowledge to translate essential findings into novel treatment strategies. This review aims to address new therapeutic modalities emerging from preclinical studies offering a unique translational opportunity for NB treatment.

A Numerical Investigation of Aeroacoustic Fan Blade Flutter

2003 ◽  
Author(s):  
X. Wu ◽  
M. Vahdati ◽  
A. I. Sayma ◽  
M. Imregun
Keyword(s):  
Research Effort ◽  
Pressure Rise ◽  
Acoustic Properties ◽  
Pressure Amplitude ◽  
Ongoing Research ◽  
Blade Flutter ◽  
Fan Blade ◽  
Underlying Mechanisms ◽  
Flutter Margin

This paper reports the results of an ongoing research effort to explain the underlying mechanisms for aeroacoustic fan blade flutter. Using a 3D integrated aeroelasticity method and a single passage blade model that included a representation of the intake duct, the pressure rise vs. mass flow characteristic of a fan assembly was obtained for the 60%–80% speed range. A novel feature was the use of a downstream variable-area nozzle, an approach that allowed the determination of the stall boundary with good accuracy. The flutter stability was predicted for the 2 nodal diameter assembly mode arising from the first blade flap mode. The flutter margin at 64% speed was predicted to drop sharply and the instability was found to be independent of stall effects. On the other hand, the flutter instability at 74% speed was found to be driven by flow separation. Further post-processing of the results at 64% speed indicated significant unsteady pressure amplitude build-up inside the intake at the flutter condition, thus highlighting the link between the acoustic properties of the intake duct and fan blade flutter.

Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness

2021 ◽  
Vol 70 (5) ◽  
pp. 23-36
Author(s):  
Ekaterina A. Kondratyeva ◽  
Alina O. Ivanova ◽  
Maria I. Yarmolinskaya ◽  
Elena G. Potyomkina ◽  
Natalya V. Dryagina ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Serum ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Unresponsive Wakefulness Syndrome ◽  
Level Of Consciousness ◽  
Chronic Disorders ◽  
Minimally Conscious ◽  
Chronic Disorders Of Consciousness

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation. AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness. MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid. RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state. CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.

Development of High Temperature Liquid Metal Heat Transfer Fluids for CSP Applications

2014 ◽  
Author(s):  
Gopinath R. Warrier ◽  
Y. Sungtaek Ju ◽  
Jan Schroers ◽  
Mark Asta ◽  
Peter Hosemann
Keyword(s):  
Heat Transfer ◽  
High Temperature ◽  
Liquid Metal ◽  
Liquid Metals ◽  
Research Effort ◽  
Structural Materials ◽  
Forced Flow ◽  
Oxygen Control ◽  
Ongoing Research ◽  
Heat Transfer Fluids

In response to the DOE Sunshot Initiative to develop low-cost, high efficiency CSP systems, UCLA is leading a multi-university research effort to develop new high temperature heat transfer fluids capable of stable operation at 800°C and above. Due to their operating temperature range, desirable heat transfer properties and very low vapor pressure, liquid metals were chosen as the heat transfer fluid. An overview of the ongoing research effort is presented. Development of new liquid metal coolants begins with identification of suitable candidate metals and their alloys. Initial selection of candidate metals was based on such parameters as melting temperature, cost, toxicity, stability/reactivity Combinatorial sputtering of the down selected candidate metals is used to fabricate large compositional spaces (∼ 800), which are then characterized using high-throughput techniques (e.g., X-ray diffraction). Massively parallel optical methods are used to determine melting temperatures. Thermochemical modeling is also performed concurrently to compliment the experimental efforts and identify candidate multicomponent alloy systems that best match the targeted properties. The modeling effort makes use of available thermodynamic databases, the computational thermodynamic CALPHAD framework and molecular-dynamics simulations of molten alloys. Refinement of available thermodynamics models are performed by comparison with available experimental data. Characterizing corrosion in structural materials such as steels, when using liquid metals, and strategies to mitigate them are an integral part of this study. The corrosion mitigation strategy we have adopted is based on the formation of stable oxide layers on the structural metal surface which prevents further corrosion. As such oxygen control is crucial in such liquid metal systems. Liquid metal enhanced creep and embrittlement in commonly used structural materials are also being investigated. Experiments with oxygen control are ongoing to evaluate what structural materials can be used with liquid metals. Characterization of the heat transfer during forced flow is another key component of the study. Both experiments and modeling efforts have been initiated. Key results from experiments and modeling performed over the last year are highlighted and discussed.

scholarly journals Practice guideline update recommendations summary: Disorders of consciousness

Neurology ◽  
2018 ◽  
Vol 91 (10) ◽  
pp. 450-460 ◽  
Author(s):  
Joseph T. Giacino ◽  
Douglas I. Katz ◽  
Nicholas D. Schiff ◽  
John Whyte ◽  
Eric J. Ashman ◽  
...  
Keyword(s):  
Vegetative State ◽  
Persistent Vegetative State ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Case Definition ◽  
Disorders Of Consciousness ◽  
Family Counseling ◽  
Delphi Consensus ◽  
Post Injury ◽  
Term Care

ObjectiveTo update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition on minimally conscious state (MCS) and provide care recommendations for patients with prolonged disorders of consciousness (DoC).MethodsRecommendations were based on systematic review evidence, related evidence, care principles, and inferences using a modified Delphi consensus process according to the AAN 2011 process manual, as amended.RecommendationsClinicians should identify and treat confounding conditions, optimize arousal, and perform serial standardized assessments to improve diagnostic accuracy in adults and children with prolonged DoC (Level B). Clinicians should counsel families that for adults, MCS (vs vegetative state [VS]/unresponsive wakefulness syndrome [UWS]) and traumatic (vs nontraumatic) etiology are associated with more favorable outcomes (Level B). When prognosis is poor, long-term care must be discussed (Level A), acknowledging that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the Coma Recovery Scale–Revised can assist prognostication in adults (Level B); no tests are shown to improve prognostic accuracy in children. Pain always should be assessed and treated (Level B) and evidence supporting treatment approaches discussed (Level B). Clinicians should prescribe amantadine (100–200 mg bid) for adults with traumatic VS/UWS or MCS (4–16 weeks post injury) to hasten functional recovery and reduce disability early in recovery (Level B). Family counseling concerning children should acknowledge that natural history of recovery, prognosis, and treatment are not established (Level B). Recent evidence indicates that the term chronic VS/UWS should replace permanent VS, with duration specified (Level B). Additional recommendations are included.

Non-Invasive Rhythmic Musical-Electric Trigeminal Nerve Stimulation Improves Consciousness in Patients with Disorders of Consciousness

2021 ◽  
Author(s):  
Min Wu ◽  
Benyan Luo ◽  
Yamei Yu ◽  
Xiaoxia Li ◽  
Jian Gao ◽  
...  
Keyword(s):  
Trigeminal Nerve ◽  
Nerve Stimulation ◽  
Brain Activity ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Non Invasive ◽  
Trigeminal Nerve Stimulation ◽  
Novel Approach ◽  
Minimally Conscious

Abstract Disorders of consciousness (DOC) are often accompanied by aberrant oscillatory neural activity in the thalamus and cerebral cortex. Patient-friendly non-invasive treatments targeting this functional anomaly are still missing. We propose and validate a novel approach that aims to restore DOC patients’ thalamocortical oscillations by combining rhythmic trigeminal-nerve stimulation (TNS) with comodulated musical stimulation. In a cluster-randomized, placebo-controlled, double-blinded, pretest-posttest clinical study, we show that application of this multisensory approach for 40 min on five consecutive days reliably leads to long-lasting improvements in DOC patients’ consciousness (assessed with Coma Recovery Scale-Revised) and oscillatory brain activity at the musical-electric TNS frequency (assessed with electroencephalography and a novel rhythmic auditory-speech paradigm). We found diagnostic improvement in 47% of patients in minimally conscious state and a positive relationship between patients’ behavioral and neural improvements. Based on this evidence we argue that non-invasive musical-electric TNS may serve as an effective patient-friendly DOC treatment and suggest frequency-specific oscillatory neural enhancement as its mode of action.

scholarly journals Covert Cognition in Disorders of Consciousness: A Meta-Analysis

2020 ◽  
Vol 10 (12) ◽  
pp. 930
Author(s):  
Caroline Schnakers ◽  
Michaela Hirsch ◽  
Enrique Noé ◽  
Roberto Llorens ◽  
Nicolas Lejeune ◽  
...  
Keyword(s):  
Observational Studies ◽  
Functional Neuroimaging ◽  
Vegetative State ◽  
Meta Analysis ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Demographic Variables ◽  
Disorders Of Consciousness ◽  
Minimally Conscious ◽  
Increase Sample Size

Covert cognition in patients with disorders of consciousness represents a real diagnostic conundrum for clinicians. In this meta-analysis, our main objective was to identify clinical and demographic variables that are more likely to be associated with responding to an active paradigm. Among 2018 citations found on PubMed, 60 observational studies were found relevant. Based on the QUADAS-2, 49 studies were considered. Data from 25 publications were extracted and included in the meta-analysis. Most of these studies used electrophysiology as well as counting tasks or mental imagery. According to our statistical analysis, patients clinically diagnosed as being in a vegetative state and in a minimally conscious state minus (MCS−) show similar likelihood in responding to active paradigm and responders are most likely suffering from a traumatic brain injury. In the future, multi-centric studies should be performed in order to increase sample size, with similar methodologies and include structural and functional neuroimaging in order to identify cerebral markers related to such a challenging diagnosis.

Disorders of Consciousness and Neuro-Palliative Care

2015 ◽  
Author(s):  
Joseph J. Fins ◽  
Maria Masters
Keyword(s):  
Palliative Care ◽  
Brain Injury ◽  
Minimally Conscious State ◽  
Conscious State ◽  
Disorders Of Consciousness ◽  
Right To Die ◽  
Severe Brain Injury ◽  
Brain States ◽  
The Right ◽  
Minimally Conscious

This chapter explains how neuro-palliative care can be provided to patients with severe brain injury. Before arguing that the right to die must be preserved and that the right to care for patients who are minimally conscious must be supported, it defines and reviews brain states that constitute disorders of consciousness along with their differential biology. It then gives an overview of palliative care for patients with severe brain injury and the challenges involved in diagnosing the minimally conscious state. It proceeds by discussing advances in technology, particularly neuroimaging, that may help meet the needs of such patients. It also considers the neuroethics of diagnosis and concludes by suggesting ways to integrate the needs of individuals suffering from disorders of consciousness in both the local and national palliative care infrastructure.

scholarly journals Synthesis and Antitumor Evaluation of Novel Bis-Triaziquone Derivatives

Molecules ◽  
2009 ◽  
Vol 14 (7) ◽  
pp. 2306-2316 ◽  
Author(s):  
Cheng Hua Huang ◽  
Hsien-Shou Kuo ◽  
Jia-Wen Liu ◽  
Yuh-Ling Lin
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Research Effort ◽  
Normal Skin ◽  
Normal Fibroblast ◽  
Cytotoxic Activities ◽  
Design Synthesis ◽  
Human Carcinoma ◽  
Ongoing Research ◽  
Lc50 Value

Aziridine-containing compounds have been of interest as anticancer agents since late 1970s. The design, synthesis and study of triaziquone (TZQ) analogues with the aim of obtaining compounds with enhanced efficacy and reduced toxicity are an ongoing research effort in our group. A series of bis-type TZQ derivatives has been prepared and their cytotoxic activities were investigated. The cytotoxicity of these bis-type TZQ derivatives were tested on three cancer lines, including breast cancer (BC-M1), oral cancer (OEC-M1), larynx epidermal cancer (Hep2) and one normal skin fibroblast (SF). Most of these synthetic derivatives displayed significant cytotoxic activities against human carcinoma cell lines, but weak activities against SF. Among tested analogues the bis-type TZQ derivative 1a showed lethal effects on larynx epidermal carcinoma cells (Hep2), with an LC50 value of 2.02 mM, and also weak cytotoxic activity against SF cells with an LC50 value over 10 mM for 24 hr treatment. Comparing the viability of normal fibroblast cells treated with compound 1a and TZQ, the LC50 value of the latter was 2.52 mM, indicating more toxicity than compound 1a. This significantly decreased cytotoxicity of compound 1a towards normal SF cells, while still maintaining the anticancer activity towards Hep2 cells is an interesting feature. Among the seven compounds synthesized, compound 1c has similar toxicity effects on the three cancer cell lines and SF normal cells as the TZQ monomer.

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