Advances in the genetic classification of amyotrophic lateral sclerosis

Purpose of review Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease wherein disease risk and severity are, for the majority of patients, the product of interaction between multiple genetic and environmental factors. We are in a period of unprecedented discovery with new large-scale genome-wide association study (GWAS) and accelerating discovery of risk genes. However, much of the observed heritability of ALS is undiscovered and we are not yet approaching elucidation of the total genetic architecture, which will be necessary for comprehensive disease subclassification. Recent findings We summarize recent developments and discuss the future. New machine learning models will help to address nonlinear genetic interactions. Statistical power for genetic discovery may be boosted by reducing the search-space using cell-specific epigenetic profiles and expanding our scope to include genetically correlated phenotypes. Structural variation, somatic heterogeneity and consideration of environmental modifiers represent significant challenges which will require integration of multiple technologies and a multidisciplinary approach, including clinicians, geneticists and pathologists. Summary The move away from fully penetrant Mendelian risk genes necessitates new experimental designs and new standards for validation. The challenges are significant, but the potential reward for successful disease subclassification is large-scale and effective personalized medicine

Expected performance of the ASTRI-SST-2M telescope prototype

ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is an Italian flagship project pursued by INAF (Istituto Nazionale di Astrofisica) strictly linked to the development of the Cherenkov Telescope Array, CTA. Primary goal of the ASTRI program is the design and production of an end-to-end prototype of a Small Size Telescope for the CTA sub-array devoted to the highest gamma-ray energy region. The prototype, named ASTRI SST-2M, will be tested on field in Italy during 2014. This telescope will be the first Cherenkov telescope adopting the double reflection layout in a Schwarzschild-Couder configuration with a tessellated primary mirror and a monolithic secondary mirror. The collected light will be focused on a compact and light-weight camera based on silicon photo-multipliers covering a 9.6 deg full field of view. Detailed Monte Carlo simulations have been performed to estimate the performance of the planned telescope. The results regarding its energy threshold, sensitivity and angular resolution are shown and discussed.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223

Discovery of a bipolar and highly variable mass outflow from the symbiotic binary StHa 190

A highly and rapidly variable bipolar mass outflow from StHa 190 has been discovered, the first time in a yellow symbiotic star. Permitted emission lines are flanked by symmetrical jet features and multi-component P-Cyg profiles, with velocities up to 300 km/sec. Given the high orbital inclination of the binary, if the jets leave the system nearly perpendicular to the orbital plane, the de-projected velocity equals or exceeds the escape velocity (1000 km/sec). StHa190 looks quite peculiar in many other respects: the hot component is an O-type sub-dwarf without an accretion disk or a veiling nebular continuum and the cool component is a G7 III star rotating at a spectacular 105 km/sec unseen by a large margin in field G giants.Comment: Letter to the Editor, Astron.Astrophys, in pres

Opinion dynamics: models, extensions and external effects

Recently, social phenomena have received a lot of attention not only from social scientists, but also from physicists, mathematicians and computer scientists, in the emerging interdisciplinary field of complex system science. Opinion dynamics is one of the processes studied, since opinions are the drivers of human behaviour, and play a crucial role in many global challenges that our complex world and societies are facing: global financial crises, global pandemics, growth of cities, urbanisation and migration patterns, and last but not least important, climate change and environmental sustainability and protection. Opinion formation is a complex process affected by the interplay of different elements, including the individual predisposition, the influence of positive and negative peer interaction (social networks playing a crucial role in this respect), the information each individual is exposed to, and many others. Several models inspired from those in use in physics have been developed to encompass many of these elements, and to allow for the identification of the mechanisms involved in the opinion formation process and the understanding of their role, with the practical aim of simulating opinion formation and spreading under various conditions. These modelling schemes range from binary simple models such as the voter model, to multi-dimensional continuous approaches. Here, we provide a review of recent methods, focusing on models employing both peer interaction and external information, and emphasising the role that less studied mechanisms, such as disagreement, has in driving the opinion dynamics. [...]Comment: 42 pages, 6 figure

Congenital nephrogenic diabete insipidus: a new genetic mutation in a newborn

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Severe Hypernatremia as Presentation of Netherton Syndrome

Netherton syndrome is a rare, multisystem, autosomal recessive genodermatosis characterized by a triad of manifestations: congenital ichthyosis, immune dysregulation, and scalp anomalies. We report the case of a 1-month-old male infant evaluated for failure to thrive and feeding difficulties. At birth, the infant was admitted to intensive care for severe hypernatremia (natremia 186 mg/dL). Upon entering the ward, the general conditions were poor. He presented with diffuse erythrodermia. A dermatological evaluation showed evidence of “invaginated trichuriasis,” a typical sign of Netherton syndrome. Netherton syndrome is caused by a genetic mutation causing loss of function of the SPINK5 gene it encodes for the LEKTI protein, normally expressed in epithelia. Loss of LEKTI induces severe skin barrier defect. The history of the disease is characterized by serious potential complications in the first months of life, such as the risk of hypernatremic dehydration induced by high skin permeability, recurrent and/or severe infections, and growth retardation

Pseudotumor cerebri syndrome (PTCS): clinical analysis on a cohort of 37 pediatric subjects

OBJECTIVE: Pseudotumor Cerebri Syndrome (PTCS) is defined by the whole of signs and symptoms caused by elevated intracranial pressure of unclear etiology in the setting of normal brain parenchyma and cerebrospinal fluid. The diagnostic workup is important to differentiate this disorder from other conditions including brain tumors. The aim of this study is to emphasize the role of clinical signs as well as ophthalmologic evaluation for an accurate diagnosis, and to present a case-series of 37 children affected by this condition. PATIENTS AND METHODS: A retrospective study review has been performed using the medical records of the hospitalized children in the Policlinico-Vittorio Emanuele-G. Rodolico, Pediatric Units of Catania (Italy) from October 2005 to February 2020. The study was conducted ethically in accordance with World Medical Association Declaration of Helsinki and was approved by the Ethic Committee of the University of Catania, Italy (Catania 1 Clinical Registration n 138877/PO). We identified 37 children who were diagnosed with PTCS. In all the subjects, diagnosis Intracranial Idiopathic Hypertension has been verified in accordance to the Friedman 2013 criteria. Subjects with secondary intracranial hypertension have been excluded. RESULTS: A total of 37 subjects were included in this study, with a mean age, at the time of the admission, of 10 ± 3.5 years (range 4-18 years). Among these children, 56.7% were female (21 female/16 male) and almost all were overweight and/or obese (35/37, 94.5%). The most frequent symptoms were headache, vomiting and paralysis of the VI cranial nerve. In 16.2% of the cases, headache was not reported, 8.1% were asymptomatic and 5.4% had not manifested papilledema.  CONCLUSIONS: In this study group, obesity and overweight were the main risk factors of intracranial Idiopathic hypertension, regardless of gender and age of the children. A different gender distribution was observed in the two groups of children based on age and pubertal development: Female gender was a risk factor for children over 10 years old and/or in pubertal stage, while the male gender was predominant in younger and/or prepubertal children. Our data suggest that, even if a minority, there is a number of children that remains under-diagnosed with a greater potential risk of developing long-term complications