Weather Simulation of Extreme Precipitation Events Inducing Slope Instability Processes over Mountain Landscapes

Mountain landscapes are characterised by a very variable environment under different points of view (topography, geology, meteorological conditions), and they are frequently affected by mass wasting processes. A debris flow that occurred along the Croso stream, located in the Italian Lepontine Alps in the Northern Ossola Valley, during summer 2019, was analysed from a geological/geomorphological and meteorological point of view. The debris flow was triggered by an intense precipitation event that heavily impacted a very restricted area over the course of three hours. A previous debris flow along the same stream occurred in Autumn 2000, but it was related to an intense and prolonged rainfall event. The slope was characterised in terms of sediment connectivity, and data were retrieved and elaborated from the Web-GIS (Web-Geographic Information System) database of the IFFI-Italian Landslide Inventory and historical archives of landslides. Both the events were analysed through the weather research and forecasting (WRF) model applying a very high horizontal grid spacing with the aim of catching the precipitation patterns and timings. The obtained results are compared with the observed precipitation at a selection of weather stations in the area. The simulation of WRF that measured the timing in total precipitation and in its minor steps could be considered reliable. Moreover, it reveals to be appropriate for detecting in advance the meteorological conditions potentially triggering mass-wasting processes affecting slopes featuring high connectivity conditions and lithotypes characterised by a high Landslide Susceptibility Index

Development of an LC-DAD-MS-Based Method for the Analysis of Hydroxyanthracene Derivatives in Food Supplements and Plant Materials

Products based on plants containing hydroxyanthracene derivatives (HADs)-such as Rheum, Cassia, and Aloe species-are widely used in food supplements or nutraceuticals due to their laxative effects. A more restricted control of HAD contents in food supplements has been implemented by EU Regulation 2021/468, in order to increase the safety of these preparations. Due to their toxicity, aloin A, aloin B, aloe emodin, emodin, and the synthetic derivative danthron have been listed as prohibited substances in food supplements, being tolerated in amounts < 1 mg kg(-1) in marketed products. In this work, we report the development of a sensitive and fast LC-DAD-MS-based procedure for the determination of these five compounds in food supplements and plant materials or extracts. The entire procedure includes a simple sample preparation step, where target analytes are concentrated by means of solvent extraction and evaporative concentration (solid samples), or by lyophilisation (liquid samples). The average LOQ of 0.10 mg/L, LOD of 0.03 mg/L, accuracy, and precision with CVs below 12.72 were obtained for the studied analytes. This method is suitable for assessing the compliance of commercial products and raw materials with EU Regulation 2021/468. Furthermore, the proposed method can represent a starting point for the development of a unique and standardised analytical approach for the determination of other HADs under the attention of EU authorities

The globular clusters-stellar haloes connection in early type galaxies

This paper explores if, and to what an extent, the stellar populations of early type galaxies can be traced through the colour distribution of their globular cluster systems. The analysis, based on a galaxy sample from the Virgo ACS data, is an extension of a previous approach that has been successful in the cases of the giant ellipticals NGC 1399 and NGC 4486, and assumes that the two dominant GC populations form along diffuse stellar populations sharing the cluster chemical abundances and spatial distributions. The results show that a) Integrated galaxy colours can be matched to within the photometric uncertainties and are consistent with a narrow range of ages; b) The inferred mass to luminosity ratios and stellar masses are within the range of values available in the literature; c) Most globular cluster systems occupy a thick plane in the volume space defined by the cluster formation efficiency, total stellar mass and projected surface mass density. The formation efficiency parameter of the red clusters shows a dependency with projected stellar mass density that is absent for the blue globulars. In turn, the brightest galaxies appear clearly detached from that plane as a possible consequence of major past mergers; d) The stellar mass-metallicity relation is relatively shallow but shows a slope change at $M_*\approx 10^{10} M_\odot$. Galaxies with smaller stellar masses show predominantly unimodal globular cluster colour distributions. This result may indicate that less massive galaxies are not able to retain chemically enriched intestellar matter.Comment: 19 pages, 10 figure

The MOSDEF survey:AGN multi-wavelength identification, selection biases and host galaxy properties

We present results from the MOSFIRE Deep Evolution Field (MOSDEF) survey on the identification, selection biases, and host galaxy properties of 55 X-ray, IR and optically-selected active galactic nuclei (AGN) at $1.4 < z < 3.8$. We obtain rest-frame optical spectra of galaxies and AGN and use the BPT diagram to identify optical AGN. We examine the uniqueness and overlap of the AGN identified at different wavelengths. There is a strong bias against identifying AGN at any wavelength in low mass galaxies, and an additional bias against identifying IR AGN in the most massive galaxies. AGN hosts span a wide range of star formation rate (SFR), similar to inactive galaxies once stellar mass selection effects are accounted for. However, we find (at $\sim 2-3\sigma$ significance) that IR AGN are in less dusty galaxies with relatively higher SFR and optical AGN in dusty galaxies with relatively lower SFR. X-ray AGN selection does not display a bias with host galaxy SFR. These results are consistent with those from larger studies at lower redshifts. Within star-forming galaxies, once selection biases are accounted for, we find AGN in galaxies with similar physical properties as inactive galaxies, with no evidence for AGN activity in particular types of galaxies. This is consistent with AGN being fueled stochastically in any star-forming host galaxy. We do not detect a significant correlation between SFR and AGN luminosity for individual AGN hosts, which may indicate the timescale difference between the growth of galaxies and their supermassive black holes

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Therapeutic approaches for portal biliopathy: A systematic review

Portal biliopathy (PB) is defined as the presence of biliary abnormalities in patients with non-cirrhotic/non-neoplastic extrahepatic portal vein obstruction (EHPVO) and portal cavernoma (PC). The pathogenesis of PB is due to ab extrinseco compression of bile ducts by PC and/or to ischemic damage secondary to an altered biliary vascularization in EHPVO and PC. Although asymptomatic biliary abnormalities can be frequently seen by magnetic resonance cholangiopancreatography in patients with PC (77%-100%), only a part of these (5%-38%) are symptomatic. Clinical presentation includes jaundice, cholangitis, cholecystitis, abdominal pain, and cholelithiasis. In this subset of patients is required a specific treatment. Different therapeutic approaches aimed to diminish portal hypertension and treat biliary strictures are available. In order to decompress PC, surgical porto-systemic shunt or transjugular intrahepatic porto-systemic shunt can be performed, and treatment on the biliary stenosis includes endoscopic (Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy, balloon dilation, stone extraction, stent placement) and surgical (bilioenteric anastomosis, cholecystectomy) approaches. Definitive treatment of PB often requires multiple and combined interventions both on vascular and biliary system. Liver transplantation can be considered in patients with secondary biliary cirrhosis, recurrent cholangitis or unsuccessful control of portal hypertension