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The paper is the third of a series dedicated to the ab initio description of monopole giant resonances in mid-mass closed- and open-shell nuclei via the so-called projected generator coordinate method. The present focus is on the computation of the moments m k of the monopole strength distribution, which are used to quantify its centroid energy and dispersion. First, the capacity to compute low-order moments via two different methods is developed and benchmarked for the m 1 moment. Second, the impact of the angular momentum projection on the centroid energy and dispersion of the monopole strength is analysed before comparing the results to those obtained from consistent quasi-particle random phase approximation calculations. Next, the so-called energy weighted sum rule (EWSR) is investigated. First, the appropriate ESWR in the center-of-mass frame is derived analytically. Second, the intrinsic EWSR is tested in order to quantify the (unwanted) local-gauge symmetry breaking of the presently employed chiral effective field theory (χ EFT) interactions. Finally, the infinite nuclear matter incompressibility associated with the employed χ EFT interactions is extracted by extrapolating the finite-nucleus incompressibility computed from the monopole centroid energy. [ABSTRACT FROM AUTHOR]

Promoting the diversity of biological communities in areas of agricultural production is a very current debate since protected areas may not be sufficient to ensure biodiversity conservation. Among the biological communities affected by the production areas are birds, which show rapid responses to changes in the landscape. Here we seek to understand how landscape planning, concerning its composition and configuration, in areas with a matrix of planted Eucalyptus spp. forests influences the functional diversity of bird assemblages in the Atlantic Forest. Our results show that the spatial distribution design of planted forests in terms of age, land cover and clone types have effects on bird diversity with regard to functional divergence, functional evenness and species richness. These results reinforce the importance of good management for the maintenance of bird diversity. We found that bird functional diversity in planted forest matrices increased with the proximity index, proportion of native vegetation and age importance value, and is negatively influenced by edge density and proportion of forest plantation. For bird conservation, it is thus better to associate Eucalyptus spp. with other cover types in the landscape. These results corroborate that, to increase bird functional diversity, it is possible to associate conservation and production in the same landscape. Mosaic landscapes have great potential to contribute to the conservation of bird biodiversity outside protected areas. However, decisions regarding the management of planted forests and planning of improved areas intended for conservation seem to be decisive to ensure the maintenance of bird biodiversity. [ABSTRACT FROM AUTHOR]

The article discusses the use of neuroimaging to differentiate between different upper motor neuron (UMN) disorders, specifically hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and primary lateral sclerosis (PLS). The authors report that the motor band sign, a T2* signal hypointensity in the primary motor cortex, is more prevalent in patients with ALS and PLS compared to HSP. They provide follow-up data on two HSP patients with the motor band sign and also analyze a group of HSP patients who may present with features resembling ALS. The study suggests that the motor band sign can be a useful tool in the early diagnosis of motor neuron diseases. [Extracted from the article]

Many recent studies have shown that Fractal Dimension (FD), a ratio for figuring out the complexity of a system given its measurements, can be used as an useful index to provide information about certain brain disease. Our research focuses on the Alzheimer's disease changes in white and grey brain matters detected through the FD indexes of their contours. Data used in this study were obtained from the Alzheimer's Disease (AD) Neuroimaging Initiative database (Normal Condition, N = 57, and Alzheimer's Disease, N = 60). After standard preprocessing pipeline, the white and grey matter 3D FD indexes are computed for the two groups. A statistical analysis shows that only grey matter 3D FD indexes are able to differentiate healthy and AD subjects. Although white matter 3D FD indexes do not, it is remarkable that their presence enhance the separation capability of previous ones. In order to valuate the classification capability of these indexes on healthy and AD subjects, we define several Neural Networks models. The performances of these models vary according to the statistical analysis and reach their best performances when each 3D FD input index is changed into a sequence of 2D FD indexes of (a subset of) the horizontal slices of the white and grey matter volumes. [ABSTRACT FROM AUTHOR]

Background: M1a disease represents an intermediate status between loco-regional relapse and bone metastatic disease. Metastasis directed therapy (MDT), through stereotactic body RT (SBRT) may be offered to patients, aiming to exclusively treat sites of macroscopic relapse and avoiding wide prophylactic treatment volumes. This appears as a viable treatment, especially after the rise of PSMA tailored treatment approaches. Materials and methods: Data about patients treated in two different institutions were retrieved from a prospectively collected dataset. All included patients were affected by oligo-recurrent M1a disease after definitive RT or radical prostatectomy, defined as ≤ 3 nodal lesions situated above aortic bifurcation and below renal arteries. Both castration resistant PCa (CRPC) and castration sensitive (CSPC) PCa patients were included. All imaging methods were allowed to detect recurrence (CT scan, Choline or PSMA PET/CT).All sites of recurrences were treated with SBRT. Results: Median PFS was 10 months (95% CI 8–17). Twelve patients died, with a median OS of 114 months (95% CI 85–114). Out of the 83 recurrences, 2 (2.4%), 11 (13.25%), 36 (43.37%) and 15 (18%) patients had respectively prostate bed only, pelvic nodal, para-aortic or distant relapse. Furthermore, 19 (22.9%) patients experienced a biochemical only relapse with negative imaging at re-staging. Discussion: MDT conferred a remarkable PFS outcome in a mixed cohort of CSPC and CRPC patients with m1a disease, with an optimal safety profile. Prospective trials are needed in order to compare MDT and ENRT for these patients, allowing to select the best treatment option. [ABSTRACT FROM AUTHOR]

Extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated cephalosporinase (AmpC)-producing Enterobacterales (ESBL/AmpC-E) are an increasing healthcare problem in both human and veterinary medicine. The aim of this study was to investigate the possible sharing of ESBL/AmpC-E strains between healthy companion animals and humans of the same household in Portugal (PT) and the United Kingdom (UK). In a prospective longitudinal study, between 2018 and 2020, faecal samples were collected from healthy dogs (n=90), cats (n=20) and their cohabiting humans (n=119) belonging to 41 PT and 44 UK households. Samples were screened for the presence of ESBL/AmpC-E and carbapenemase-producing bacteria. Clonal relatedness between animal and human strains was established by using REP-PCR fingerprinting method, followed by whole-genome sequencing (WGS) of selected strains. ESBL/AmpC-E strains were detected in companion animals (PT=12.7%, n=8/63; UK=8.5%, n=4/47) and humans (PT=20.7%, n=12/58; UK=6.6%, n=4/61) in at least one timepoint. REP-PCR identified paired multidrug-resistant ESBL/AmpC-producing Escherichia coli strains from companion animals and owners in two Portuguese households (4.8%) and one UK household (2.3%). WGS analysis of nine E. coli strains from these three households confirmed that interhost sharing occurred only between the two animal-human pairs from Portugal. Three shared strains were identified: one CTX-M-15-producing E. coli strain in a cat-human pair (O15-H33-ST93) and two CTX-M-15- and CTX-M-55/CMY-2-producing E. coli strains, in a dog-human pair (O8:H9-ST410 and O11:H25-ST457, respectively) at different timepoints. These E. coli clonal lineages are human pandemic, highlighting the role of companion animals living in close contact with humans in the dissemination and persistence of antimicrobial resistance in the household environment. [ABSTRACT FROM AUTHOR]

Recent advances in machine learning have highlighted the importance of using group equivariant non-expansive operators for building neural networks in a more transparent and interpretable way. An operator is called equivariant with respect to a group if the action of the group commutes with the operator. Group equivariant non-expansive operators can be seen as multi-level components that can be joined and connected in order to form neural networks by applying the operations of chaining, convex combination and direct product. In this paper we prove that each linear G-equivariant non-expansive operator (GENEO) can be produced by a weighted summation associated with a suitable permutant measure, provided that the group G transitively acts on a finite signal domain. This result is based on the Birkhoff–von Neumann decomposition of doubly stochastic matrices and some well known facts in group theory. Our theorem makes available a new method to build all linear GENEOs with respect to a transitively acting group in the finite setting. This work is part of the research devoted to develop a good mathematical theory of GENEOs, seen as relevant components in machine learning. [ABSTRACT FROM AUTHOR]

Given a 3-uniform hypergraph H having a set V of vertices, and a set of hyperedges T ⊂ P (V) , whose elements have cardinality three each, a null labelling is an assignment of ± 1 to the hyperedges such that each vertex belongs to the same number of hyperedges labelled + 1 and - 1 . A sufficient condition for the existence of a null labelling of H (proved in Di Marco et al. Lect Notes Comput Sci 12757:282–294, 2021) is a Hamiltonian cycle in its 2-intersection graph. The notion of 2-intersection graph generalizes that of intersection graph of an (hyper)graph and extends its effectiveness. The present study first shows that this sufficient condition for the existence of a null labelling in H can not be weakened by requiring only the connectedness of the 2-intersection graph. Then some interesting properties related to their clique configurations are proved. Finally, the main result is proved, the NP-completeness of this characterization and, as a consequence, of the construction of the related 3-hypergraphs. [ABSTRACT FROM AUTHOR]

Recently, ab initio techniques have been successfully connected to the traditional valence-space shell model. In doing so, they can either explicitly provide ab initio shell-model effective Hamiltonians or constrain the construction of empirical ones. In the present work, the possibility to follow a similar path for the nuclear energy density functional (EDF) method is analyzed. For this connection to be actualized, two theoretical techniques are instrumental: the recently proposed ab initio PGCM-PT many-body formalism and the MR-IMSRG pre-processing of the nuclear Hamiltonian. Based on both formal arguments and numerical results, possible new lines of research are briefly discussed, namely to compute ab initio EDF effective Hamiltonians at low computational cost, to constrain empirical ones or to produce them directly via an effective field theory that remains to be invented. [ABSTRACT FROM AUTHOR]

Objectives: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. Methods: We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated. Results: The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases). Conclusions: Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients. Key Points: • The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence. • Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity. • The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes. [ABSTRACT FROM AUTHOR]

Riparian deforestation degrades stream habitats, altering fish assemblages' structure, and composition. In contrast, secondary riparian forests can recover stream habitats and fish assemblages as they recover structural attributes and ecological processes. We evaluated whether the amount and condition of secondary riparian forests were important to conserve fish assemblages in 49 streams sites in eastern Amazonia. We related fish assemblage taxonomic and functional measures to riparian forest amount plus different habitat metrics using regression analysis. We compared assemblage measures among reference forests, abandoned pastures (open canopy), and secondary forests (closed canopy) using ANOVA tests. The amount of secondary forests had little influence on fish assemblages. Species richness, diversity, and functional richness were higher in pasture than in reference sites but returned to pre-disturbance conditions in secondary sites. However, functional evenness was lower in pasture streams and did not recover after secondary forest regrowth. Our results show that secondary riparian forest condition is important to recover some aspects of fish assemblages. However, streams bordered by these forests may have impoverished fish assemblages because some lost sensitive species may take longer to return. Avoiding riparian deforestation is the best strategy to reduce losses in aquatic biodiversity and ecosystem functions in tropical agricultural landscapes. [ABSTRACT FROM AUTHOR]

A remarkable family of discrete sets which has recently attracted the attention of the discrete geometry community is the family of convex polyominoes, that are the discrete counterpart of Euclidean convex sets, and combine the constraints of convexity and connectedness. In this paper we study the problem of their reconstruction from orthogonal projections, relying on the approach defined by Barcucci et al. (Theor Comput Sci 155(2):321–347, 1996). In particular, during the reconstruction process it may be necessary to expand a convex subset of the interior part of the polyomino, say the polyomino kernel, by adding points at specific positions of its contour, without losing its convexity. To reach this goal we consider convexity in terms of certain combinatorial properties of the boundary word encoding the polyomino. So, we first show some conditions that allow us to extend the kernel maintaining the convexity. Then, we provide examples where the addition of one or two points causes a loss of convexity, which can be restored by adding other points, whose number and positions cannot be determined a priori. [ABSTRACT FROM AUTHOR]

Reconstructing a discrete object by means of X-rays along a finite set U of (discrete) directions represents one of the main task in discrete tomography. Indeed, it is an ill-posed inverse problem, since different structures exist having the same projections along all lines whose directions range in U. Characteristic of ambiguous reconstructions are special configurations, called switching components, whose understanding represents a main issue in discrete tomography, and an independent interesting geometric problem as well. The investigation of switching component usually bases on some kind of prior knowledge that is incorporated in the tomographic problem. In this paper, we focus on switching components under the constraint of convexity along the horizontal and the vertical directions imposed to the unknown object. Moving from their geometric characterization in windows and curls, we provide a numerical description, by encoding them as special sequences of integers. A detailed study of these sequences leads to the complete understanding of their combinatorial structure, and to a polynomial-time algorithm that explicitly reconstructs any of them from a pair of integers arbitrarily given. [ABSTRACT FROM AUTHOR]

A nonnegative integer sequence is k-graphic if it is the degree sequence of a k-uniform simple hypergraph. The problem of deciding whether a given sequence π is 3-graphic has recently been proved to be NP-complete, after years of studies. Thus, it acquires primary relevance to detect classes of degree sequences whose graphicality can be tested in polynomial time in order to restrict the NP-hard core of the problem and design algorithms that can also be useful in different research areas. Several necessary and few sufficient conditions for π to be k-graphic, with k ≥ 3 , appear in the literature. Frosini et al. defined a polynomial time algorithm to reconstruct k-uniform hypergraphs having regular or almost regular degree sequences. Our study fits in this research line providing a combinatorial characterization of span-two sequences, i.e., sequences of the form π = (d , ... , d , d - 1 , ... , d - 1 , d - 2 , ... , d - 2) , d ≥ 2 , which are degree sequences of some 3-uniform hypergraphs. Then, we define a polynomial time algorithm to reconstruct one of the related 3-uniform hypergraphs. Our results are likely to be easily generalized to k ≥ 4 and to other families of degree sequences having simple characterization, such as gap-free sequences. [ABSTRACT FROM AUTHOR]

Circulating tumor cells detection and ARV7 expression are associated with worse clinical outcomes in metastatic Castration-Resistant Prostate Cancer (mCRPC) undergoing Androgen Receptor Targeted Agents. ARFL, PSMA and PSA may help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCPRC undergoing I line ARTA therapy terminated the planned enrollment in 2020. Here, we present a pre-planned interim analysis with 18 months of median follow-up. RT-qPCR was used to determine the CTC expression of PSA, PSMA, AR and ARV7 before starting ARTA. PSA-drop, Progression-Free and Overall Survival (PFS and OS) and their correlation with CTC detection were reported. Forty-four patients were included. CTC were detected in 43.2% of patients, of whom 8.94% expressed PSA, 15.78% showed ARV7, 63.15% and 73.68% displayed ARFL and PSMA, respectively. Biochemical response was significantly improved in CTC + vs CTC- patients, with median PSA-drop of 18.5 vs 2.5 ng/ml (p = 0.03). After a median follow-up of 18 months, 50% of patients progressed. PFS was significantly longer in CTC- patients (NR vs 16 months). Eight (18.2%) patients died, a non-significant trend in terms of OS was detected in favor of CTC- patients (NR vs 29 months, p = 0.05). AR, PSA and PSMA expression in CTC + had no significant impact on PSA-drop, PFS or OS. PRIMERA-trial confirmed the CTC detection predictive importance in mCRPC patients. [ABSTRACT FROM AUTHOR]

The emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is a potent Fc-engineered monoclonal antibody (mAb) able to neutralize in vitro all current SARS-CoV-2 variants of concern (VoCs) including the omicron variant even if with significantly reduced potency. Here we evaluated data obtained from the first 30 days of a phase 1 clinical study (EudraCT N.: 2020-005469-15 and ClinicalTrials.gov Identifier: NCT04932850). The primary endpoint evaluated the percentage of severe adverse events. Secondary endpoints evaluated pharmacokinetic and serum neutralization titers. A single dose administration of MAD0004J08 via intramuscular (i.m.) route is safe and well tolerated, resulting in rapid serum distribution and sera neutralizing titers higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralize major SARS-CoV-2 variants of concern (alpha, beta, gamma and delta). MAD0004J08 can be a major advancement in the prophylaxis and clinical management of COVID-19. Monoclonal antibodies (mAbs) are a potential therapeutic option for treatment of COVID-19. Here, the authors report safety and pharmacokinetics of an intramuscularly injected mAb (MAD0004J08) during the first 30 days of a phase 1 clinical study. [ABSTRACT FROM AUTHOR]

The neon isotopic chain displays a rich phenomenology, ranging from clustering in the ground-state of the self-conjugate doubly open-shell stable 20 Ne isotope to the physics of the island of inversion around the neutron-rich 30 Ne isotope. This second (i.e. Paper II) of the present series proposes an extensive ab initio study of neon isotopes based on two complementary many-body methods, i.e. the quasi-exact in-medium no-core shell model (IM-NCSM) and the projected generator coordinate method (PGCM) that is ideally suited to capturing strong static correlations associated with shape deformation and fluctuations. Calculations employ a state-of-the-art generation of chiral effective field theory Hamiltonians and evaluate the associated systematic uncertainties. In spite of missing so-called dynamical correlations, which can be added via the multi-reference perturbation theory proposed in the first paper (i.e. Paper I) of the present series [1], the PGCM is shown to be a suitable method to tackle the low-lying spectroscopy of complex nuclei. Still, describing the physics of the island of inversion constitutes a challenge that seems to require the inclusion of dynamical correlations. This is addressed in the third paper (i.e. Paper III) of the present series [2]. [ABSTRACT FROM AUTHOR]

In spite of missing dynamical correlations, the projected generator coordinate method (PGCM) was recently shown to be a suitable method to tackle the low-lying spectroscopy of complex nuclei. Still, describing absolute binding energies and reaching high accuracy eventually requires the inclusion of dynamical correlations on top of the PGCM. In this context, the present work discusses the first realistic results of a novel multi-reference perturbation theory (PGCM-PT) that can do so within a symmetry-conserving scheme for both ground and low-lying excited states. First, proof-of-principle calculations in a small ( e max = 4 ) model space demonstrate that exact binding energies of closed- ( 16 O ) and open-shell ( 18 O , 20 Ne ) nuclei are reproduced within 0.5– 1.5 % at second order, i.e. through PGCM-PT(2). Moreover, profiting from the pre-processing of the Hamiltonian via multi-reference in-medium similarity renormalization group transformations, PGCM-PT(2) can reach converged values within smaller model spaces than with an unevolved Hamiltonian. Doing so, dynamical correlations captured by PGCM-PT(2) are shown to bring essential corrections to low-lying excitation energies that become too dilated at leading order, i.e., at the strict PGCM level. The present work is laying the foundations for a better understanding of the optimal way to grasp static and dynamical correlations in a consistent fashion, with the aim of accurately describing ground and excited states of complex nuclei via ab initio many-body methods. [ABSTRACT FROM AUTHOR]

Perturbative and non-perturbative expansion methods already constitute a tool of choice to perform ab initio calculations over a significant part of the nuclear chart. In this context, the categories of accessible nuclei directly reflect the class of unperturbed state employed in the formulation of the expansion. The present work generalizes to the nuclear many-body context the versatile method of Burton and Thom (J Chem Theory Comput 16(4):5586, 2020) by formulating a perturbative expansion on top of a multi-reference unperturbed state mixing deformed non-orthogonal Bogoliubov vacua, i.e. a state obtained from the projected generator coordinate method (PGCM). Particular attention is paid to the part of the mixing taking care of the symmetry restoration, showing that it can be exactly contracted throughout the expansion, thus reducing significantly the dimensionality of the linear problem to be solved to extract perturbative corrections. While the novel expansion method, coined as PGCM-PT, reduces to the PGCM at lowest order, it reduces to single-reference perturbation theories in appropriate limits. Based on a PGCM unperturbed state capturing (strong) static correlations in a versatile and efficient fashion, PGCM-PT is indistinctly applicable to doubly closed-shell, singly open-shell and doubly open-shell nuclei. The remaining (weak) dynamical correlations are brought consistently through perturbative corrections. This symmetry-conserving multi-reference perturbation theory is state-specific and applies to both ground and excited PGCM unperturbed states, thus correcting each state belonging to the low-lying spectrum of the system under study. The present paper is the first in a series of three and discusses the PGCM-PT formalism in detail. The second paper displays numerical zeroth-order results, i.e. the outcome of PGCM calculations. Second-order, i.e. PGCM-PT(2), calculations performed in both closed- and open-shell nuclei are the object of the third paper. [ABSTRACT FROM AUTHOR]

The computational cost of ab initio nuclear structure calculations is rendered particularly acute by the presence of (at least) three-nucleon interactions. This feature becomes especially critical now that many-body methods aim at extending their reach beyond mid-mass nuclei. Consequently, state-of-the-art ab initio calculations are typically performed while approximating three-nucleon interactions in terms of effective, i.e. system-dependent, zero-, one- and two-nucleon operators. While straightforward in doubly closed-shell nuclei, existing approximation methods based on normal-ordering techniques involve either two- and three-body density matrices or a symmetry-breaking one-body density matrix in open-shell systems. In order to avoid such complications, a simple, flexible, universal and accurate approximation technique involving the convolution of the initial operator with a sole symmetry-invariant one-body matrix is presently formulated and tested numerically. Employed with a low-resolution Hamiltonian, the novel approximation method is shown to induce errors below 2 - 3 % across a large range of nuclei, observables and many-body methods. [ABSTRACT FROM AUTHOR]

Background: Progressive supranuclear palsy (PSP) is an atypical Parkinsonism characterized by motor and neuropsycological disorders. Language could be impaired in PSP patients, also in Richardson variant (PSP-RS). The analysis of connected speech is used in neurodegenerative disorder to investigate different levels of language organization, including phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic processing. Objective: In our study, we aimed to investigate the language profile, especially connected speech, in early-stage PSP-RS and Parkinson's disease (PD) patients without predominant speech or language disorders. Methods: Language was assessed using the Screening for Aphasia in NeuroDegeneration (SAND); connected speech analysis was conducted from the picture description subtest. Results: We enrolled 48 patients, 22 PD and 26 PSP (18 PSP-RS and 8 non-RS). PSP-RS patients presented an impairment in language domain, particularly regarding connected speech. PSP-RS patients presented worse performances than PD in different scores. The output of PSP-RS patients was characterized by a reduction in number of sentences and subordinates with respect to PD; PSP presented also more repaired sequences and phonological and lexico-semantic errors than PD. Number of sentences and number of subordinates of the picture description task were identified as predictors of PSP diagnosis. Conclusion: In summary, the SAND scale is able to identify language impairment in PSP patients. The analysis of connected speech could highlight some important aspects of language impairment in PSP-RS patients, and it could be helpful in the differential diagnosis with PD. [ABSTRACT FROM AUTHOR]

Background: If Parkinson's Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD patients. Objective: In the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine. Method: A case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored. Results: Out of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (p < 0.001) and diabetes (p = 0.049) compared to non-COVID-19. In non-COVID-19 PD population (n = 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases. Conclusion: A higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it. [ABSTRACT FROM AUTHOR]

Astrocyte activation is characterized by hypertrophy with increased glial fibrillary acidic protein (GFAP), whose expression may involve pro-inflammatory cytokines. In this study, the effects of pro-inflammatory IL-6 and TNF-α and anti-inflammatory cytokines IL-4 and IL-10 on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling, intracellular calcium concentration ([Ca2+]i) and GFAP expression were investigated. In human glioblastoma astrocytoma U-373 MG cells, IL-6 and TNF-α, but not IL-4 or IL-10, increased iNOS, cGMP, [Ca2+]i and GFAP expression. The inhibitors of iNOS (1400 W), soluble guanylyl cyclase (ODQ) and IP3 receptors (ryanodine and 2-APB) reversed the increase in cGMP or [Ca2+]i, respectively, and prevented GFAP expression. In rat striatal slices, IL-6 and TNF-α, at variance with IL-4 and IL-10, promoted a concentration-dependent increase in Ca2+ efflux, an effect prevented by 1400 W, ODQ and RY/2APB. These data were confirmed by in vivo studies, where IL-6, TNF-α or the NO donor DETA/NO injected in the striatum of anaesthetised rats increased cGMP levels and increased GFAP expression. The present findings point to NO/cGMP-dependent calcium signalling as part of the mechanism mediating IL-6- and TNF-α-induced GFAP expression. As this process plays a fundamental role in driving neurotoxicity, targeting NO/cGMP-dependent calcium signalling may constitute a new approach for therapeutic interventions in neurological disorders. [ABSTRACT FROM AUTHOR]

Service composition and supporting transactions across composed services are among the major challenges characterizing service-oriented computing. REpresentational State Transfer (REST) is one of the approaches used for implementing Web services that is gaining momentum thanks to its features making it suitable for cloud computing and microservices-based contexts. This paper introduces ReLock, a resilient RESTful transaction model introducing general purpose transactions on RESTful services by a layered approach and a two-phase locking mechanism not requesting any change to the RESTful services involved in a transaction. [ABSTRACT FROM AUTHOR]

Since the first particle accelerator's construction in 1931, an exponential spread of these machines occurred worldwide, in different kinds of applications. Nowadays, these are mainly used for industrial (60%) and medical (35%) purposes and for scientific research (5%). High energy secondary mixed fields produced by the particle beams interaction with matter imply a complex environmental dosimetry and special radiation protection regulations able to guarantee workers and population safety. In the medical field, this aspect is particularly emphasized in hadrontherapy centres, where high energy charged particles such as protons and carbon ions modify environmental doses, with a significant increase in the neutron contribution. This work proposes a technique to identify points of losses of the primary particle beam around an acceleration ring and has been developed within the radiation protection section at the National Centre for Oncological Hadrontherapy situated in Pavia. In the first part, the radiation field produced by protons and carbon ions interactions with structural materials at different energies was investigated. The main instrument of analysis is the Monte Carlo code for particle transport FLUKA, supported by experimental measurements in the treatment room carried out with the rem counter LUPIN, designed for pulsed neutron fields dosimetry. This first step allowed an analysis of both the angular and energetic instrumental response and a comparison of experimental results with simulations. The second part proposes a description of the technique for beam loss positions reconstruction around the acceleration ring at CNAO based on the application of unfolding codes. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage. 123I-FP-CIT-SPECT was believed to be helpful in this regard, however its role in predicting surgical outcome has been disputed. We illustrate a patient presented with gait disturbance, urinary incontinence, and asymmetrical parkinsonian signs, who underwent a 3T brain MRI and a 123I-FP-CIT-SPECT. VPS was performed. The patient repeated a 123I-FP-CIT-SPECT, 18 months after the operation, and was clinically followed up for 24 months. Our patient displayed clinical and radiological criteria for iNPH and an abnormal asymmetrical uptake in 123I-FP-CIT-SPECT, consistent with her asymmetrical parkinsonism. However, the organization of the substantia nigra studied with iron-sensitive sequences in 3T brain MRI scan appeared intact. The patient revealed an improvement both clinically and in 123I-FP-CIT-SPECT at postsurgical follow-up. Our report suggests that abnormal 123I-FP-CIT-SPECT may not necessarily reveal an overlap with neurodegenerative parkinsonism; its partial reversibility may suggest that the mechanical effect exerted on the striatum by ventriculomegaly ultimately leads to downregulation of dopaminergic transporters which may improve after VPS. [ABSTRACT FROM AUTHOR]

Theory of mind (ToM) is the ability to attribute mental states to one self and others and to understand that others have beliefs different from one's own. Different subcomponents of ToM have also been identified: cognitive and affective. Cognitive ToM refers to the capacity to infer others' beliefs and intentions, while affective ToM implies the ability to appreciate others' emotional states. The aim of this study was to explore ToM in drug-naïve Parkinson's disease (PD) patients and to investigate the effects of chronic dopaminergic therapy on different subcomponents of ToM during a 3 months and 1 year of follow-up. We examined 16 PD patients in three conditions: before (un-medicated) and after dopaminergic therapy (medicated 3 months: T1 and medicated 1 year: T2). We also compared our PD's ToM abilities with 11 healthy individuals. ToM was explored with 5 different tasks: Faux Pas Test, Picture Sequencing Task Capture Story, Emotion Attribution Task, Strange Stories Task, and Karolinska Directed Emotional Faces. Our study confirms that PD patients present deficits in cognitive components of ToM and preserved performances in the affective ones in early stages of disease. We also find a significant effect of dopaminergic therapy on ToM already after 3 months with a good persistency after 1 year of treatment. [ABSTRACT FROM AUTHOR]

Background: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP.Methods and Results: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach's alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts.Conclusion: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers' everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach's alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients' severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients. [ABSTRACT FROM AUTHOR]

A plethora of complex misfolded protein combinations have been found in Alzheimer disease (AD) brains besides the classical pathological hallmarks. Recently, α-synuclein (α-syn) and its heterocomplexes with amyloid-β (Aβ) and tau have been suggested to be involved in the pathophysiological processes of neurodegenerative diseases. These pathological features are not limited to the brain, but can be also found in peripheral fluids. In this respect, red blood cells (RBCs) have been suggested as a good model to investigate the biochemical alterations of neurodegeneration. Our aim is to find whether RBC concentrations of α-syn and its heterocomplexes (i.e., α-syn/Aβ and α-syn/tau) were different in AD patients compared with healthy controls (HC). The levels of homo- and heteroaggregates of α-syn, Aβ and tau, were analyzed in a cohort of AD patients at early stage either with dementia or prodromal symptoms (N = 39) and age-matched healthy controls (N = 39). All AD patients received a biomarker-based diagnosis (low cerebrospinal fluid levels of Aβ peptide combined with high cerebrospinal fluid concentrations of total tau and/or phospho-tau proteins; alternatively, a positivity to cerebral amyloid-PET scan). Our results showed lower concentrations of α-syn and its heterocomplexes (i.e., α-syn/Aβ and α-syn/tau) in RBCs of AD patients with respect to HC. RBC α-syn/Aβ as well as RBC α-syn/tau heterodimers discriminated AD participants from HC with fair accuracy, whereas RBC α-syn concentrations differentiated poorly the two groups. Although additional investigations are required, these data suggest α-syn heteroaggregates in RBCs as potential tool in the diagnostic work-up of early AD diagnosis. [ABSTRACT FROM AUTHOR]

The Game of Dice Task (GDT; Brand et al. in Neuropsychology 19:267-277, 2005a; Psychiatry Res 133:91-99, 2005b) measures decision-making under objective risk conditions. Although disadvantageous decision-making has been shown in individuals with substance dependency, such as pathological dependency, any studies have been conducted with adolescents by using the GDT to investigate the relationship between the performance on the task and gambling behavior. Moreover, all the previous studies have considered only the GDT net score and not the single choices. In the current study, focusing on adolescents, we wanted to investigate the relationship between the sequence of the choices at the GDT and gambling behavior, measured with the SOGS-RA. To analyze the predictive power of the sequence of choices made in the GDT and problem gambling and gambling frequency, we used the Neural Networks (NNs), which are often used to find relationships between a series of input actions and the correspondent empirical outputs in order to discover behavioral patterns that may be predictive of at-risk behaviors. Results showed that neither a linear or a non-linear relationship could be detected between the GDT performance and the SOGS-RA classification both in terms of gambling problem severity and gambling frequency. Indeed, different training algorithms produced different performances of the NN on the training sets, but all of them showed a very low prediction capability on new samples. Thus, the performance at the GDT did not discriminate between adolescent gamblers with different and progressive levels of problematic gambling behavior and gambling frequency. Limitations and future studies are discussed. [ABSTRACT FROM AUTHOR]

The welfare of farmed animals, and more recently of farmed fish, is a growing concern in current society. Changes in living conditions represent one of the most stressful situations in fish production. It is crucial to develop tools to evaluate welfare in farmed fish throughout the various situations observed during the production cycle. The present work aims to select relevant parameters in order to evaluate the welfare of trout, by describing the physiological and zootechnical profiles of rainbow trout Oncorhynchus mykiss (Walbaum) populations during adaptation to a new environment. Ten days after transferring seven groups of farmed trout to a laboratory setting, a principal component analysis was performed on five parameters: plasma cortisol level (PCL), hepatosomatic index (HI), growth (G), food intake (FI) and food conversion ratio (FCR). PCL and FCR were positively correlated and were both negatively correlated with FI and G. FI and G were positively correlated. HI was not correlated with any other parameter. PCL was considered as being at basal levels. Descriptive statistics and the principal component analysis suggest measuring PCL, G, FI and FCR to be a relevant strategy for evaluating the welfare of trout when adapting to a new environment. The study demonstrates the relevance of this approach in evaluating specific profiles related to the welfare of farmed animals. [ABSTRACT FROM AUTHOR]

Daily PM10 aerosol samples were collected at the Gruvebadet observatory, Ny-Ålesund (Svalbard Islands), during the spring-summer 2014 Italian Arctic Campaign. A total of 136 samples were analysed for ion (inorganic anions and cations, selected organic anions) composition aiming to evaluate the seasonal pattern of sulfate, as a key component of the Arctic haze. Ionic balances indicated a strong sulfate seasonality with mean spring concentration about 1.5 times higher than that measured in summer. The spring and summer aerosol was almost neutral, indicating that ammonia was the major neutralizing agent for atmospheric acidic species. The linear regression between sulfate from potential acidic sources (non-sea salt sulfate and non-crustal sulfate) and ammonium indicated that the mean sulfate/ammonium ratio was intermediate between semi-(NHHSO) and complete ((NH)SO) neutralization. Using sea-salt sodium as sea-spray marker, non-sea-salt calcium as crustal marker and methanesulfonic acid as biogenic marker, a detailed source apportionment for sulfate was carried out. The anthropogenic input (calculated as the differences between total sulfate and the sum of sea-salt, crustal and biogenic contributes) was found to be the most relevant contribution to the sulfate budget in the Ny-Ålesund aerosol in summer and, especially, in spring. In this last season, crustal, sea-salt, biogenic and anthropogenic sources accounted for 3.3, 12.0, 11.5 and 74.8 %, respectively. [ABSTRACT FROM AUTHOR]

During the 2013 Arctic campaign, direct measurements and size-segregated samplings of atmospheric aerosol were carried out from March to September at the Gruvebadet observatory in Ny-Ålesund (78°56′N, 11°56′E; Svalbard Islands). Continuous size distribution measurements (104 size classes) were performed both in the nano- (TSI-SMPS system) and micro-metric (TSI-APS device) range with a resolution of 10 min. Aerosol sampling was carried out on daily basis (PM fraction, 00:01-23:59 UTC) and with a 4-day resolution (four-stage cascade impactor). A back-trajectory analysis was performed for specific events to understand transport processes and possible source areas of aerosol reaching Ny-Ålesund. Aerosol samples were analyzed for ion composition (inorganic cations and anions, selected organic anions) by a three-chromatograph system after extraction in ultra-sonic bath. Special attention was spent in identifying and interpreting the seasonal pattern of natural and anthropic chemical markers. Sea spray aerosol was evenly distributed along all the sampling period with maxima related to wind speed. Its size distribution peaks in 1.0-2.5 or 2.5-10 µm, depending on the transport conditions and distance from source areas. Anthropic sulfate dominates the spring aerosol load (Arctic Haze), both in acidic form (HSO) and in partially or totally neutralized ammonium salts. Biogenic contributions, marked by methanesulfonic acid, are relatively relevant in late spring-early summer and are distributed in the finest aerosol fraction (<1.0 µm). [ABSTRACT FROM AUTHOR]

Asymmetrical N, N-bis(alkanol)amine aryl esters (FRA77, GDE6, and GDE19) are potent multidrug resistance (MDR) reversers. Their structures loosely remind that of the Ca antagonist verapamil. Therefore, the aim of this study was to investigate their vascular activity in vitro. Their effects on the mechanical activity of fresh and cultured rat aorta rings on Ca1.2 channel current ( I ) of A7r5 cells and their cytotoxicity on A7r5 and EA.hy926 cells were analyzed. Docking at the rat α subunit of the Ca1.2 channel was simulated in silico. Compounds tested were cytotoxic at concentrations >1 μM (FRA77, GDE6, GDE19) and >10 μM (verapamil) in EA.hy926 cells, or >10 μM (FRA77, GDE6, GDE19) and at 100 μM (verapamil) in A7r5 cells. In fresh rings, the three compounds partly antagonized phenylephrine and 60 mM K (K60)-induced contraction at concentrations ≥1 and ≥3 μM, respectively. On the contrary, verapamil fully relaxed rings pre-contracted with both agents. In cultured rings, 10 μM GDE6, GDE19, FRA77, and verapamil significantly reduced the contractile response to both phenylephrine and K60. Similarly to verapamil, the three compounds docked at the α subunit, interacting with the same amino acids residues. FRA77, GDE6, and GDE19 inhibited I with IC values 1 order of magnitude higher than that of verapamil. FRA77-, GDE6-, and GDE19-induced vascular effects occurred at concentrations that are at least 1 order of magnitude higher than those effectively reverting MDR. Though an unambiguous divergence between MDR reverting and vascular activity is of overwhelming importance, these findings consistently contribute to the design and synthesis of novel and potent chemosensitizers. [ABSTRACT FROM AUTHOR]

Ten healthy subjects (HS) and 15 patients with atypical parkinsonisms underwent 7-T susceptibility-weighted-imaging MR to evaluate substantia nigra (SN). All HS were judged 'normal'. Twelve out of 15 patients exhibited bilateral abnormal SN while three patients with corticobasal degeneration (CBD) showed bilateral normal aspect of SN. Anatomical changes of SN at 7 T occur in multiple system atrophy and progressive supranuclear palsy as previously reported in Parkinson's disease. Preserved SN in CBD confirms the pathological heterogeneity of this disease. [ABSTRACT FROM AUTHOR]