GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems of the DS detectors, designed to detect the residual ionization from such collisions

Trombocytopenic trombotica purpura (ttp) and metalloproteinase (mmp1). role for a possible proctetive effect

Background. Thrombocytopenic Trombotic purpura (TTP) is a rare disease. In TTP high concentration of multimeric factors cause platelet aggregations. The von willebrant factor (vwf) is a protein synthesized by endothelium and megakaryocytic is present in multimeric forms. Metalloproteinase are involved in cartilage proteolysis and participate in other processes of matrix cellular disruption. Objective. To evaluate polymorphism state in MMP1 (Matrix metalloproteinase-1) promoter gene in heterozygous or homozygous conditions and clinical correspondenceto TTP. Materials and methods. Forty-two consecutive cases with primary Thrombocytopenic trombotic purpura, median 42 year, range 43-82), 29 female, and 13 male were evaluated. DNA was collected from peripheral blood in mono nucleated cells. Saline method with small modification for DNA dried slides extraction was used. PCR method for transcript of a disintegrin and metalloprotease with thrombospondin type I domains 13(ADAMTS13) and beta actin controls were used. For study of MMP1 gene, polymorphism PCR method, and enzymatic ALU I digestions and agarose gel electrophoresis evaluation were used. Results were compared (case control analysis) to 150 (ratio 1:3.5) Sardinian control, matched for age, geographic zone and sex. Results. All transcripts for ADAMTS 13 were positive. The genotype analysis in patients groups (n=42) reveal 3/42 (7,1%) 2G/2G genotype, 25/42 (59.5%) 1G/2G , 14/42 (33,3%) 1G/1G. While in controls (n=150) were 50/150 (33.3%)2G/2G genotype, 66/150 (44.4%)1G/2G genotype, 33/150 (22.2%)1G/1G genotype respectively. Then, from 42/42 cases evaluation was evinced significative (X=7.5808, p=0.005). Respect control groups. On the basis of this observation the 2G/2G patient groups, we suppose a co-operative action between protheolitic activity of collagenase of MMP1 and reduced activity of ADAMTS 13. This could be originated from an increase of transcription activity of MMP1 with an increase of collagenase quantity. This 2G/2G genotype, could be s protective towards TTP disease. In addition and a prompt response to plasmapheresis did not present any relapse in 11,11, 8 years of continuous of follow-up respectively

DarkSide-50, a background free experiment for dark matter searches

The existence of dark matter is inferred from gravitational effects, but its nature remains a deep mystery. One possibility, motivated by considerations in elementary particle physics, is that dark matter consists of elementary particles, such as the hypothesized Weakly Interacting Massive Particles (WIMPs), with mass ~ 100 GeV and cross-section ~ 10−47 cm2, that can be gravitationally trapped inside our galaxy and revealed by their scattering on nuclei. It should be possible to detect WIMPs directly, as the orbital motion of the WIMPs composing the dark matter halo pervading the galaxy should result in WIMP-nucleus collisions of sufficient energy to be observable in the laboratory. The DarkSide-50 experiment is a direct WIMP search using a Liquid Argon Time Projection Chamber (LAr-TPC) with an active mass of 50 kg with a high sensitivity and an ultra-low background detector

First Results from the DarkSide-50 Dark Matter Experiment at Laboratori Nazionali del Gran Sasso

We report the first results of DarkSide-50, a direct search for dark matter operating in the un- derground Laboratori Nazionali del Gran Sasso (LNGS) and searching for the rare nuclear recoils possibly induced by weakly interacting massive particles (WIMPs). The dark matter detector is a Liquid Argon Time Projection Chamber with a ( 46.4 0.7 ) kg active mass, operated inside a 30 t or- ganic liquid scintillator neutron veto, which is in turn installed at the center of a 1 kt water Cherenkov veto for the residual flux of cosmic rays. We report here the null results of a dark matter search for a ( 1422 67 ) kg d exposure with an atmospheric argon fill. This is the most sensitive dark matter search performed with an argon target, corresponding to a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 6.1 1

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

It is generally inferred from astronomical measurements th at Dark Matter (DM) comprises approximately 27% of the energy-dens ity of the universe. If DM is a subatomic particle, a possible candidate is a Weakl y Interacting Mas- sive Particle (WIMP), and the DarkSide-50 (DS) experiment i s a direct search for evidence of WIMP-nuclear collisions. DS is located undergr ound at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of thr ee active, embedded components; an outer water veto (CTF), a liquid scintillato r veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This pap er describes the data acquisition and electronic systems of the DS detectors , designed to detect the residual ionization from

Neutron Stars and Black Holes in X-ray Binaries

Galactic accretion driven stellar X-ray sources can be divided into groups in different ways. An important division, which covers almost all known X-ray binaries, can be made according to the mass of the donor star: high-mass X-ray binaries and low-mass X-ray binaries. Another distinction (partially overlapping with the previous one) can be made on the basis of the nature of the accreting object: a strongly magnetized neutron star, a neutron star with a weak magnetic field, or a black hole. In this review I describe the properties of these different types of X-ray binaries, and discuss the mass determinations which are the basis for distinguishing accreting neutron stars from black holes.Comment: 58 pages, 15 figures. To be published in 'The Many Faces of Neutron Stars', R. Buccheri, J. van Paradijs, M.A. Alpar (Eds), Kluwer Academic Publisher

Measurement of the Cosmic Ray e(+)+e(-) Spectrum from 20 GeV to 1 TeV with the Fermi Large Area Telescope

Designed as a high-sensitivity gamma-ray observatory, the Fermi Large Area Telescope is also an electron detector with a large acceptance exceeding 2 m2 sr at 300 GeV. Building on the gamma-ray analysis, we have developed an efficient electron detection strategy which provides sufficient background rejection for measurement of the steeply falling electron spectrum up to 1 TeV. Our high precision data show that the electron spectrum falls with energy as E-3.0 and does not exhibit prominent spectral features. Interpretations in terms of a conventional diffusive model as well as a potential local extra component are briefly discussed