Abstract The tailings dump of Barraxiutta (Sardinia, Italy) contains considerable concentrations of heavy metals and, consequently, is scarcely colonized by plants. However, wild populations of the ...liverwort Lunularia cruciata (L.) Dum. form dense and healthy‐looking carpets on this tailing dump. L. cruciata colonizing the tailing dump was compared with a control population growing in a pristine environment in terms of: (i) pollutant content, (ii) photochemical efficiency, and (iii) volatile secondary metabolites in thalli extracts. L. cruciata maintained optimal photosynthesis despite containing considerable amounts of soil pollutants in its thalli and had higher sesquiterpene content compared to control plants. Sesquiterpenes have a role in plant stress resistance and adaptation to adverse environments. In the present study, we propose enhanced sesquiterpenes featuring Contaminated L. cruciata as a defence strategy implemented in the post‐mining environment.
On March 10, 2017, the US Securities and Exchange Commission (SEC) issued an order (the BZX Order) disapproving a rule change that Bats BZX Exchange (BZX) had proposed to list and trade shares issued ...by the Winklevoss Bitcoin Trust.1 On March 28, 2017, the SEC issued another order (the NYSE Arca Order, together with the BZX Order, the Orders) disapproving a rule change that NYSE Arca had proposed to list and trade shares of the SolidX Bitcoin Trust.2 The Orders do not allow securities with bitcoin as the underlying asset to be traded on a national securities exchange because of the SEC's concern that bitcoin markets are unregulated and susceptible to manipulation. The trusts planned to issue and redeem the shares to authorized participants.4 The investment objective of the trusts would be for the shares to track the price of bitcoins traded on a separate bitcoin exchange (in the case of BZX's proposal) or the price of bitcoins as measured by TradeBlock XBX index (in the case of NYSE Arca's proposal), which represents the value of one bitcoin in US dollars drawing on bitcoin trading data from constituent bitcoin exchanges.5 In connection with its proposal, BZX entered into a surveillance-sharing agreement with the separate bitcoin exchange.6 The SEC disapproved both proposed rule changes because regulators did not find the proposals to be consistent with Section 6(b)(5) of the Securities Exchange Act of 1934 (the Exchange Act), which requires, among other things, that the rules of a national securities exchange be...
Consciousness constitutes a fundamental prerequisite in the individual appraisal and experience of pain. In the same way, a person needs to be able to report on pain perception. Patients who suffered ...a severe brain injury with disorders of consciousness (DOC) represent a spectrum of pathologies affecting patients' capacity to interact with the external world. In these patients, the most relevant aspects in response to pain are physiologic and behavioral. The treatments and management of pain are challenging issues in these patients, arising serious ethical concerns and bringing emotional load among medical staff, caregivers, and relatives. In this review, we report the importance of having a correct pain management in DOC patients, to individuate the best pharmacological treatment that can make the difference in detecting a behavioral response, indicative of a change in the level of consciousness, and in planning a more effective rehabilitative approach.
Objective. Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use ...with severely disabled patients. Gaze-independent SSVEP-BCIs have been designed but have shown a drop in accuracy and have not been tested in brain-injured patients. In the present paper, we propose a novel independent SSVEP-BCI based on covert attention with an improved classification rate. We study the influence of feature extraction algorithms and the number of harmonics. Finally, we test online communication on healthy volunteers and patients with locked-in syndrome (LIS). Approach. Twenty-four healthy subjects and six LIS patients participated in this study. An independent covert two-class SSVEP paradigm was used with a newly developed portable light emitting diode-based 'interlaced squares' stimulation pattern. Main results. Mean offline and online accuracies on healthy subjects were respectively 85 ± 2% and 74 ± 13%, with eight out of twelve subjects succeeding to communicate efficiently with 80 ± 9% accuracy. Two out of six LIS patients reached an offline accuracy above the chance level, illustrating a response to a command. One out of four LIS patients could communicate online. Significance. We have demonstrated the feasibility of online communication with a covert SSVEP paradigm that is truly independent of all neuromuscular functions. The potential clinical use of the presented BCI system as a diagnostic (i.e., detecting command-following) and communication tool for severely brain-injured patients will need to be further explored.
The ‘default network’ is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest ...than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient’s default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology.
Tinnitus, the perception of sound in the absence of external stimuli, is often a disturbing symptom for which the underlying functional neuroanatomy still remains poorly understood. Most studies have ...focused solely on functional connectivity changes in the auditory cortex of tinnitus patients. The aim of this study was to investigate whether a correlation exists between tinnitus behavioural scores and functional brain connectivity of five resting-state networks comprising the auditory, the default mode, the external control left and right, and the salience network. For this purpose, a large sample of one hundred and thirty-five subjects underwent resting-state functional magnetic resonance imaging and their behavioural scores were obtained using clinical evaluations. Networks were extracted using independent component analysis, and functional connectivity patterns in the extracted networks were evaluated by a graph theoretical approach. The effects of tinnitus for each network were investigated by correlating the graph strength of all the regions with the tinnitus behavioural scores using stepwise fit regression analysis. Results indicated that alterations of functional interactions between key neural circuits of the brain are not limited to one single network. In particular, tinnitus distress showed a strong correlation with the connectivity pattern within and between the right executive control network and the other four resting-state networks, indicating that tinnitus distress is probably the consequence of a hyperactive attention condition. Among the behavioural scores, the strongest correlation was observed between age and hearing loss, while the tinnitus objective loudness was not correlated with any behavioural scores.
We propose the formulation and characterization of solid microparticles as nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector ...unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial-like). Nasal administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) to 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after nasal administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.
Water scarcity and water security are linked, not only through the direct effects of water shortages on each water users' access to water, but also because of water conflicts generated. Climate ...change is predicted to raise temperatures in the Mediterranean region and reduce rainfall, leading to a reduction in water yield and possibly worsening the situation of water resource shortages that Mediterranean regions are already experiencing. In its dissemination strategy, the EU FP7 CLIMB project addressed water security threats through an analysis of water uses and water use rivalries within a few target catchments distributed over the Mediterranean region. The present work explores whether climate change is locally perceived by stakeholders (water users and managers) as a key issue for their water uses and water security. Individual interviews, meetings, and compilation of questionnaires were conducted at five sites located in the Mediterranean region. The methodology permitted an analysis of water use and its evolution in the water management context, an identification of the state of awareness of local stakeholders and of the pressures on water use and water use rivalries, and a prioritization of water uses. Currently, the main response to increasing water demand in the Mediterranean region, while not yet considering climate change as a driving force, is a progressive externalization of water resources, with limits represented by national borders and technological possibilities. Overall, ‘climate change’ was not mentioned by stakeholders during both interviews and in answers to the questionnaires. Even the prospect of decreasing precipitation was not considered a relevant or threatening issue in the coming 20years. This confirms the need to continue all efforts to disseminate the state of knowledge on climate change impacts in the Mediterranean region, such as water scarcity, especially to local water managers, as initiated by various research programs of the European Commission.
•A local study of water uses, part of the CLIMB EU project dissemination strategy.•The prioritization of water uses is a potential source of rivalry.•Security of water uses is achieved but water uses are not sustainable.•The water managers have to deal with an increasing management complexity.•The challenges of climate change are not perceived by local stakeholders.
Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains ...unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease.
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