Background and purpose
Essential tremor (ET) and Parkinson's disease (PD) sometimes overlap in their clinical expression with ET preceding PD onset, often leading to misdiagnosis. Transcranial ...sonography (TCS) has been shown to be a valid and non‐invasive diagnostic tool to identify early idiopathic PD and to differentiate it from ET. The purpose of this study was to investigate the relevance of substantia nigra hyperechogenicity in patients with ET.
Methods
A total of 138 patients (79 with PD, 59 with ET) and 50 matched controls underwent TCS examination at baseline. All patients were followed in a 3‐year longitudinal assessment.
Results
A total of 10 subjects were excluded from the analysis due to the bilateral absence of a temporal acoustic window. During the follow‐up period, 11 of the patients with ET developed new‐onset parkinsonian features, without fulfilling criteria for PD diagnosis (ET+). Nine patients developed clinical features meeting diagnostic criteria for probable PD (ET‐PD). Patients with ET− did not develop parkinsonian features. For each group, the maximum size of the substantia nigra hyperechogenicity was as follows: 5.62 ± 5.40 mm2 in the control group, 19.02 ± 14.27 mm2 in patients with PD, 9.15 ± 11.26 mm2 in patients with ET−, 20.05 ± 13.78 mm2 in patients with ET+ and 20.13 ± 13.51 mm2 in patients with ET‐PD. ET‐PD maximum values were significantly different from controls. Maximum values in patients with ET+ were different from both controls and patients with ET−.
Conclusion
Substantia nigra hyperechogenicity in ET seems to represent a risk marker for developing early parkinsonian symptoms or signs in the 3 years following TCS assessment.
The cancellation of noise from terrestrial gravity fluctuations, also known as Newtonian noise (NN), in gravitational-wave detectors is a formidable challenge. Gravity fluctuations result from ...density perturbations associated with environmental fields, e.g., seismic and acoustic fields, which are characterized by complex spatial correlations. Measurements of these fields necessarily provide incomplete information, and the question is how to make optimal use of available information for the design of a noise-cancellation system. In this paper, we present a machine-learning approach to calculate a surrogate model of a Wiener filter. The model is used to calculate optimal configurations of seismometer arrays for a varying number of sensors, which is the missing keystone for the design of NN cancellation systems. The optimization results indicate that efficient noise cancellation can be achieved even for complex seismic fields with relatively few seismometers provided that they are deployed in optimal configurations. In the form presented here, the optimization method can be applied to all current and future gravitational-wave detectors located at the surface and with minor modifications also to future underground detectors.
FRB 180916 is a most intriguing source capable of producing repeating fast radio bursts with a periodic 16.3 day temporal pattern. The source is well positioned in a star-forming region in the ...outskirts of a nearby galaxy at 150 Mpc distance. In this Letter we report on the X-ray and γ-ray observations of FRB 180916 obtained by AGILE and Swift. We focused especially on the recurrent 5 day time intervals of enhanced radio bursting. In particular, we report on the results obtained in the time intervals 2020 February 3-8, 2020 February 25, 2020 March 5-10, and 2020 March 22-28 during a multiwavelength campaign involving high-energy and radio observations of FRB 180916. We also searched for temporal coincidences at millisecond timescales between the 32 known radio bursts of FRB 180916 and X-ray and MeV events detectable by AGILE. We do not detect any simultaneous event or any extended X-ray and γ-ray emission on timescales of hours/days/weeks. Our cumulative X-ray (0.3-10 keV) flux upper limit of 5 × 10−14 erg cm−2 s−1 (obtained during 5 day active intervals from several 1-2 ks integrations) translates into an isotropic luminosity upper limit of LX,UL ∼ 1.5 × 1041 erg s−1. Deep γ-ray observations above 100 MeV over a many-year timescale provide an average luminosity upper limit one order of magnitude larger. These results provide the so-far most stringent upper limits on high-energy emission from the FRB 180916 source. Our results constrain the dissipation of magnetic energy from a magnetar-like source of radius Rm, internal magnetic field Bm, and dissipation timescale τd to satisfy the relation , where Rm,6 is Rm in units of 106 cm, Bm,16 is Bm in units of 1016 G, and τd,8 in units of 108 s.
Abstract
The advanced gravitational wave interferometers are reaching unprecedented levels of strain sensitivity, that is, of accessible volume of Universe, in search for the most elusive cosmic ...sources. In this effort, the optical design of these detectors places increasingly stringent requirements on the components. Thermal effects, related to the fraction of laser beam power absorbed in the optics, and deviation of components from specifications, intrinsic to the state of art of the production processes, need to be addressed to recover the ideal operation of the detector. Ring heaters (RHs) are thermally coupled actuators conceived to precisely tune the radius of curvature (RoC) of the highly reflective surface of mirrors. The actuator concept has been improved and properly rescaled to design dedicated heaters for different mirrors of the Advanced Virgo detector (namely test masses, power and signal recycling mirrors, filter cavity mirrors). This paper describes the design features and performances of the RHs installed around the test masses of Advanced Virgo, highlighting the improvements of this design with respect to previous actuators. In this case, the dynamic actuation range reaches 100 m over a static RoC value of 1500 m, with the deformation largely dominated by the spherical component. The obtained actuation gain is
d
R
o
C
d
P
= − 0.93 m W
−1
, with a typical settling time of about 6 h.
The advanced Virgo (AdV) sensitivity might be influenced by the effects of environmental noise, in particular magnetic noise (MN). In order to show the impact on the gravitational-wave strain signal ...h(t) and on the AdV sensitivity, we must understand the coupling between the environmental magnetic activity and the strain. The relationship between the environmental noise-measured by a physical environment monitor (PEM)-and h(t) is investigated using injection studies, where an intentional stimulus is introduced and the responses of both PEM sensors and the instrument are analyzed. We also present the most outstanding measurements and results obtained from both the characterization and the mitigation studies of the environmental MN. Results show that MN does not affect AdV sensitivity up to 100 Mpc in BNS range.
GRB 190114C represents a breakthrough for the physics of gamma-ray bursts (GRBs), being the first GRB with delayed emission above 300 GeV, as reported by MAGIC. We present in this paper the ...sub-MeV/MeV data of the prompt and early afterglow emissions of GRB 190114C, as detected by AGILE and Konus-Wind, in the 20 keV-100 MeV energy range. The first stages of the burst exhibit multiple emission components, associated with an interesting spectral evolution. The first 2 s of the prompt emission can be described by a single "Band-like" spectral component. The successive 4 s show the presence of an additional high-energy spectral component, which quickly evolves into a "hard-flat" component of the F spectrum, extending up to 10-100 MeV and likely produced by inverse Compton radiation, whose onset and evolution are clearly shown in our data. After this phase, the F spectrum evolves into a "V shape," showing the persistence and spectral hardening of the additional high-energy component in substantial agreement with Fermi and Swift results. We also analyze the first ∼200 s of the early afterglow that show a reflaring episode near T0 + 15 s. We identify a new, so-far-unnoticed flux temporal break near T0 + 100 s, which is detected in hard X-rays by both Konus-Wind and INTEGRAL/SPI-ACS. We find this break incompatible with the commonly assumed adiabatic evolution of a fireball in a constant-density medium. We interpret this break as a consequence of radiative evolution of the early afterglow from a fireball expanding in a wind-like circumburst medium.
The origin of cosmic neutrinos is still largely unknown. Using data obtained by the gamma-ray imager on board the Astro-rivelatore Gamma a Immagini Leggero (AGILE) satellite, we systematically ...searched for transient gamma-ray sources above 100 MeV that are temporally and spatially coincident with 10 recent high-energy neutrino IceCube events. We found three AGILE candidate sources that can be considered possible counterparts to neutrino events. Detecting three gamma-ray/neutrino associations out of 10 IceCube events is shown to be unlikely due to a chance coincidence. One of the sources is related to the BL Lac source TXS 0506+056. For the other two AGILE gamma-ray sources there are no obvious known counterparts, and both Galactic and extragalactic origin should be considered.
In the past thirty years, nerve growth factor (NGF) has received much attention for its potential role as a therapeutic agent for Alzheimer's disease (AD) due to its neurotrophic activities on basal ...forebrain cholinergic neurons. This attention has been renewed by recent findings that provide new causal links between defects in NGF signaling, transport or processing to the activation of the amyloidogenic route and, more generally, to AD neurodegeneration. Thus, the concept of therapeutic administration of human recombinant NGF in AD patients has a strong rationale, being further validated by recent and ongoing clinical trials with a gene-therapy approach. However, the widespread clinical application of gene or cell-therapy strategies for the delivery of NGF to AD patients seems unpractical, and it would be more advantageous to have non-invasive methods, that should also limit the adverse effects of NGF in activating nociceptive responses. This review will describe: 1) the data from preclinical and clinical studies underlying the rationale of NGF as a potential therapeutic agent for AD; and 2) the alternative strategies to reach adequate concentrations of NGF in relevant brain areas while preventing the onset of adverse effects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
In the perspective of novel treatments with disease-modifying drugs, a timely diagnosis of Alzheimer’s’ disease (AD) at preclinical phase represents a major issue. To this purpose, in ...clinical setting, there is the need to detect the earliest cognitive symptoms not yet fulfilling Mild Cognitive Impairment criteria, in order to proceed to biomarker assessment for diagnostic definition. In terms of cognitive performance, Subjective Cognitive Decline (SCD) is still a controversial entity, due to the difficulty of reliably measuring subtle deficits.
Objective
To evaluate the possibility to predict the presence of AD-like CSF pattern in SCD individuals, according to their neuropsychological performance assessed by means of both traditional and computerized measures.
Design
Retrospective study.
Setting
Clinical setting (Centre for Memory Disturbances, Section of Neurology, University Hospital of Perugia, Italy).
Participants
74 consecutive SCD subjects who underwent an in-depth (paper-pencil and computerized) neuropsychological assessment and CSF analysis for AD biomarkers (Aβ42/Aβ40 ratio, phospho-tau, total tau).
Measurements
Neuropsychological assessment was composed of traditional tests assessing five cognitive domains (verbal memory, attention, executive functions, language, visuo-spatial abilities) and computerized tasks from CAmbridge Neuropsychological Test Automated Battery (CANTAB) (Pattern Recognition Memory, Paired Associates Learning and Spatial Working Memory). According to their performance at traditional tests, SCD individuals were categorized into cognitively normal (CN) and subtle impaired (SI); with respect to CANTAB, they were defined as CANTAB− in presence of normal performance, and CANTAB+ in presence of at least one pathological score. The subgroup with completely normal performance was defined as CN/CANTAB−, and the subgroup with impairment in both measures as SI/CANTAB+. Differences in prevalence of A/T/N profile according to cognitive profiles were assessed by Fisher’s exact text for count data.
Results
None of CN/CANTAB− subjects showed A+/T+ status. SI/CANTAB+ subjects showed a significantly high prevalence of A+/T+ profile (14/35, 40%, p=0.03 vs CN/CANTAB−).
Conclusion
The neuropsychological profile may be of help in identifying SCD subjects requiring biomarker assessment. If confirmed in larger cohorts, the combination of traditional and computerized tests (namely, CANTAB) might represent a feasible strategy in clinical setting for carrying out biomarker assessment in individuals before the MCI stage. Detection of AD in these subjects would give them the highest chances to halt disease progression by means of disease modifying treatments.
Children and adolescents with haematological malignancies (PedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and ...impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in PedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The "up and down stairs'' test (TUDS), "6 min walking" test (6MWT), the "5 Repetition Maximum strength" leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups (P < 0.05), while the 6MWT and balance tests showed improvement only in HAd group (P < 0.0001). These results support the ever-growing theory that, in the case of the treatment of PedHM, 'exercise is medicine' and it has the potential to increase the patient's chances of social inclusion.
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