Combining olfactory test and motion analysis sensors in Parkinson's disease preclinical diagnosis: A pilot study

Objectives: Preclinical diagnosis of Parkinson's disease (PD) is nowadays a topic of interest as the neuropathological process could begin years before the appearance of motor symptoms. Several symptoms, among them hyposmia, could precede motor features in PD. In the preclinical phase of PD, a subclinical reduction in motor skills is highly likely. In this pilot study, we investigate a step-by-step method to achieve preclinical PD diagnosis. Material and methods: We used the IOIT (Italian Olfactory Identification Test) to screen a population of healthy subjects. We identified 20 subjects with idiopathic hyposmia. Hyposmic subjects underwent an evaluation of motor skills, at baseline and after 1 year, using motion analysis sensors previously created by us. Results: One subject showed significant worsening in motor measurements. In this subject, we further conducted a dopaminergic challenge test monitored with the same sensors and, finally, he underwent [123I]-FP/CIT (DaTscan) SPECT brain imaging. The results show that he is probably affected by preclinical PD. Conclusions: Our pilot study suggests that the combined use of an olfactory test and motor sensors for motion analysis could be useful for a screening of healthy subjects to identify those at a high risk of developing PD

Crilin: A CRystal calorImeter with Longitudinal InformatioN for a future Muon Collider

The measurement of physics processes at new energy frontier experiments requires excellent spatial, time, and energy resolutions to resolve the structure of collimated high-energy jets. In a future Muon Collider, the beam-induced backgrounds (BIB) represent the main challenge in the design of the detectors and of the event reconstruction algorithms. The technology and the design of the calorimeters should be chosen to reduce the effect of the BIB, while keeping good physics performance. Several requirements can be inferred: i) high granularity to reduce the overlap of BIB particles in the same calorimeter cell; ii) excellent timing (of the order of 100 ps) to reduce the out-of-time component of the BIB; iii) longitudinal segmentation to distinguish the signal showers from the fake showers produced by the BIB; iv) good energy resolution (less than 10%/sqrt(E)) to obtain good physics performance, as has been already demonstrated for conceptual particle flow calorimeters. Our proposal consists of a semi-homogeneous electromagnetic calorimeter based on Lead Fluoride Crystals (PbF2) readout by surface-mount UV-extended Silicon Photomultipliers (SiPMs): the Crilin calorimeter. In this paper, the performances of the Crilin calorimeter in the Muon Collider framework for hadron jets reconstruction have been analyzed. We report the single components characterizations together with the development of a small-scale prototype, consisting of 2 layers of 3x3 crystals each

Megatsunamis Induced by Volcanic Landslides in the Canary Islands: Age of the Tsunami Deposits and Source Landslides

Evidence for frequent, large landslides on the flanks of the volcanic edifices forming the Canary Islands include outstanding landslide scars and their correlative submarine and subaerial rock and debris avalanche deposits. These landslides involved volumes ranging from tens to hundreds of km3. The sudden entry of large volumes of rock masses in the sea may have triggered tsunamis capable of affecting the source and neighboring islands, with the resulting huge waves dragging coastal and seabed materials and fauna and redepositing them inland. Here, we present new geological evidence and geochronological data of at least five megatsunamis in Tenerife, Lanzarote, and Gran Canaria, triggered by island flank megalandslides, and occasionally explosive eruptions, during the last 1 million years. The exceptional preservation of the megatsunami deposits and the large area they cover, particularly in Tenerife, provide fundamental data on the number of tsunami events and run-ups, and allow proposals on the sources and age of the tsunamis. Tsunami run-up heights up to 290 m above coeval sea level, some of the highest known on Earth in recent geological times, were estimated based on sedimentological, geomorphological, paleontological, and geochronological data. The research results made it possible to estimate the recurrence of tsunamis in the archipelago during the last hundreds of thousands of years, and to establish relationships between tsunami deposits and the probable triggering island flank landslides.info:eu-repo/semantics/publishedVersio

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study)

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and ‘other sites’ infections’ (OTA). Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016–2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. Results: 206 patients enrolled (males 50%, median age 62 [IQR 50–76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure. Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5–22 vs 3, 0–11.7; p<0.0001) and received longer previous (18 days, 9–30 vs 11, 7–19; p = 0.007)/concomitant antibiotic treatments (21 days, 14–52 vs 11, 8–14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% vs 75%, p = 0.459) and safety (no AE: 81.5% vs 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies. Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use

Sea level changes during the last and present interglacials in Sal Island (Cape Verde archipelago)

Last interglacial and Holocene deposits are particularly well developed in the southern parts of Sal Island (Cape Verde Archipelago). They primarily consist of low-elevation (≤2 m above sea level [a.s.l.]) marine deposits made of a basal conglomerate embedded in carbonate mud, passing upwards to calcarenites. All deposits contain an abundant fauna with corals, algae and molluscs with Strombus latus Gmelin and accompanying warm water species of the “Senegalese” fauna. Small scale geomorphological mapping with detailed morphosedimentary analysis revealed lateral facies changes and imbricate (offlapping) structures that suggest small-scale oscillations of paleo-sealevels during high sea stand intervals. U-series measurements (in coral fragments) allowed unequivocal identification of Marine Isotope Substage (MIS) 5.5 units, but were not precise enough to date the sea level oscillations of the interval. However, geomorphological data and sedimentary facies analysis suggest a double sea level highstand during the peak of the last interglacial. MIS 5.5 age deposits occur at Sal and the Canary Islands at low topographic elevations, between 1 and 2 masl. However, these values are lower than the elevations measured for the correlative terraces outcropping at the western tropical Atlantic islands, widely considered to be tectonically stable. Combining the results in this paper with earlier investigations of the “Senegalese” fauna distribution as far north as the Mediterranean basin, it is suggested that the last-interglacial oceanic temperatures in this basin, as well as the temperatures in other islands of the Eastern Atlantic and the coasts of Morocco, were warmer than modern temperatures

Beam test, simulation, and performance evaluation of PbF2_2 and PWO-UF crystals with SiPM readout for a semi-homogeneous calorimeter prototype with longitudinal segmentation

Crilin (Crystal Calorimeter with Longitudinal Information) is a semi-homogeneous, longitudinally segmented electromagnetic calorimeter based on high-$Z$, ultra-fast crystals with UV-extended SiPM readout. The Crilin design has been proposed as a candidate solution for both a future Muon Collider barrel ECAL and for the Small Angle Calorimeter of the HIKE experiment. As a part of the Crilin development program, we have carried out beam tests of small ($10\times10\times40$~mm$^3$) lead fluoride (PbF$_2$) and ultra-fast lead tungstate (PbWO$_4$, PWO) crystals with 120~GeV electrons at the CERN SPS to study the light yield, timing response, and systematics of light collection with a proposed readout scheme. For a single crystal of PbF$_2$, corresponding to a single Crilin cell, a time resolution of better than 25~ps is obtained for $>$3 GeV of deposited energy. For a single cell of \pwo, a time resolution of better than 45~ps is obtained for the same range of deposited energy. This timing performance fully satisfies the design requirements for the Muon Collider and HIKE experiments. Further optimizations of the readout scheme and crystal surface preparation are expected to bring further improvements

The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer

Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCζ is a tumor suppressor in CRC with reduced expression in metastasis. Given the importance of microRNAs (miRNAs) in regulating cellular plasticity, we performed an unbiased screening and identified the miR-200 family as the most relevant miRNAs downregulated by PKCζ deficiency. The regulation of the intracellular levels of miR-200 by PKCζ is post-transcriptional and involves their secretion in extracellular vesicles. Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing. Loss of this axis results in epithelial-to-mesenchymal transition (EMT) and increased liver metastases, which can be inhibited in vivo by blocking miR-200 release. Therefore, the PKCζ/ADAR2 axis is a critical regulator of CRC metastases through modulation of miR-200 levels.Research was supported by grants from the NIH ( R01DK108743 , R01CA172025 , and R01CA207177 to J.M.; R01CA192642 and R01CA218254 to M.T.D.-M.)