Strategic decision making under climate change: a case study on Lake Maggiore water system

Abstract. Water resources planning processes involve different kinds of decisions that are generally evaluated under a stationary climate scenario assumption. In general, the possible combinations of interventions are mutually compared as single alternatives. However, the ongoing climate change requires us to reconsider this approach. Indeed, what have to be compared are not individual alternatives, but families of alternatives, characterized by the same structural decisions, i.e. by actions that have long-term effects and entail irrevocable changes in the system. The rationale is that the structural actions, once they have been implemented, cannot be easily modified, while the management decisions can be adapted to the evolving conditions. This paper considers this methodological problem in a real case study, in which a strategic decision has to be taken: a new barrage was proposed to regulate Lake Maggiore outflow, but, alternatively, either the present barrage can be maintained with its present regulation norms or with a new one. The problem was dealt with by multi-criteria decision analysis involving many stakeholders and two decision-makers. An exhaustive set of indicators was defined in the participatory process, conducted under the integrated water resource management paradigm, and many efficient (in Pareto sense) regulation policies were identified. The paper explores different formulations of a global index to evaluate and compare the effectiveness of the classes of alternatives under both stationary and changing hydrological scenarios in order to assess their adaptability to the ongoing climate change

Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury

There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: − 30%) and external capsule (EC: − 21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (− 17%) and EC (− 13%), corresponding to histopathological evidence of white matter loss (cl-CC: − 68%; cl-EC: − 30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration

Efficacy of acute administration of inhaled argon on traumatic brain injury in mice

BACKGROUND: Whilst there has been progress in supportive treatment for traumatic brain injury (TBI), specific neuroprotective interventions are lacking. Models of ischaemic heart and brain injury show the therapeutic potential of argon gas, but it is still not known whether inhaled argon (iAr) is protective in TBI. We tested the effects of acute administration of iAr on brain oedema, tissue micro-environmental changes, neurological functions, and structural outcome in a mouse model of TBI. METHODS: Anaesthetised adult C57BL/6J mice were subjected to severe TBI by controlled cortical impact. Ten minutes after TBI, the mice were randomised to 24 h treatments with iAr 70%/O2 30% or air (iCtr). Sensorimotor deficits were evaluated up to 6 weeks post-TBI by three independent tests. Cognitive function was evaluated by Barnes maze test at 4 weeks. MRI was done to examine brain oedema at 3 days and white matter damage at 5 weeks. Microglia/macrophages activation and functional commitment were evaluated at 1 week after TBI by immunohistochemistry. RESULTS: iAr significantly accelerated sensorimotor recovery and improved cognitive deficits 1 month after TBI, with less white matter damage in the ipsilateral fimbria and body of the corpus callosum. Early changes underpinning protection included a reduction of pericontusional vasogenic oedema and of the inflammatory response. iAr significantly reduced microglial activation with increases in ramified cells and the M2-like marker YM1. CONCLUSIONS: iAr accelerates recovery of sensorimotor function and improves cognitive and structural outcome 1 month after severe TBI in adult mice. Early effects include a reduction of brain oedema and neuroinflammation in the contused tissue

A novel echocardiographic method closely agrees with cardiac magnetic resonance in the assessment of left ventricular function in infarcted mice

Cardiac Magnetic Resonance (CMR) is the gold standard for left ventricular (LV) function assessment in small rodents and, though echocardiography (ECHO) has been proposed as an alternative method, LV volumes may be underestimated when marked eccentric remodeling is present. In the present study we described a novel echocardiographic method and we tested the agreement with CMR for LV volumes and ejection fraction calculation in mice with experimental myocardial infarction. Sham-operated and infarcted mice, subjected to Coronary Artery Ligation, underwent ECHO and CMR. Volumes and ejection fraction were calculated by ECHO using a standard Simpson\u2019s modified method (ECHO pLAX) or a method from sequential parasternal short axis (ECHO pSAX) acquired mechanically by translating the probe every 1 mm along the left ventricle. The mean differences \ub11.96 standard deviation near to zero suggested close agreement between ECHO pSAX and CMR; contrarily ECHO pLAX agreement with CMR was lower. In addition, ECHO was three times shorter and cheaper (Relative cost difference: pLAX: 1266% and pSAX 1257%) than CMR. In conclusion, ECHO pSAX is a new, fast, cheap and accurate method for LV function assessment in mice

An early developmental vertebrate model for nanomaterial safety:Bridging cell-based and mammalian toxicity assessment

Background. With the rise in production of nanoparticles for an ever-increasing number of applications, there is an urgent need to efficiently assess their potential toxicity. We propose a nanoparticle hazard assessment protocol that combines mammalian cytotoxicity data with embryonic vertebrate abnormality scoring to determine an overall toxicity index. Results. We observed that, after exposure to a range of nanoparticles, Xenopus phenotypic scoring showed a strong correlation with cell based in vitro assays. Magnetite-cored nanoparticles, negative for toxicity in vitro and Xenopus, were further confirmed as non-toxic in mice. Conclusion. The results highlight the potential of Xenopus embryo analysis as a fast screening approach for toxicity assessment of nanoparticles, which could be introduced for the routine testing of nanomaterials

Spin dynamics in molecular ring nanomagnets: Significant effect of acoustic phonons and magnetic anisotropies

The nuclear spin-lattice relaxation rate 1/T_1_ is calculated for magnetic ring clusters by fully diagonalizing their microscopic spin Hamiltonians. Whether the nearest-neighbor exchange interaction J is ferromagnetic or antiferromagnetic, 1/T_1_ versus temperature T in ring nanomagnets may be peaked at around k_B_T=|J| provided the lifetime broadening of discrete energy levels is in proportion to T^3^. Experimental findings for ferromagnetic and antiferromagnetic Cu^II^ rings are reproduced with crucial contributions of magnetic anisotropies as well as acoustic phonons.Comment: 5 pages with 5 figures embedded, to be published in J. Phys. Soc. Jpn. 75, No. 10 (2006

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN–Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies

Aims: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. Methods: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. Results: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. Conclusions: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies

Aims: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. // Methods: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type specific depletion was used in a murine model of acquired epilepsy. // Results: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers, and in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. // Conclusions: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control