CAIMAN Experiment

Non-acoustic detection systems can be used in combination with Sonar systems to determine the presence of an underwater threat, such as terrorist divers. The goal of the CAIMAN (Coastal Anti Intruders MAgnetometers Network) joint experiment (Italian Navy, NATO Undersea Research Centre and INGV Marine Geophysics) is the application of High Definition Geophysics Magnetic techniques in a port protection scenario, where conventional measurements of very low magnetic sources, like intruder swimmers, are strongly disturbed by ambient, natural and artificial, background noise and other time-variant magnetic anomalies. Two tri-axial fluxgate magnetometers were deployed on the sea bottom and connected to a shore side measurement station. A team of navy divers, wearing both COTS and EOD equipment, performed some coastal approach runs on each magnetometer alternatively. Magnetic signature data were logged and post processed using MATLAB®. Results demonstrated the effectiveness of high definition time reduction techniques using a self-referred integrated array design

The Highly Miniaturised Radiation Monitor

We present the design and preliminary calibration results of a novel highly miniaturised particle radiation monitor (HMRM) for spacecraft use. The HMRM device comprises a telescopic configuration of active pixel sensors enclosed in a titanium shield, with an estimated total mass of 52 g and volume of 15 cm$^3$. The monitor is intended to provide real-time dosimetry and identification of energetic charged particles in fluxes of up to 10$^8$ cm$^{-2}$ s$^{-1}$ (omnidirectional). Achieving this capability with such a small instrument could open new prospects for radiation detection in space.Comment: 17 pages, 15 figure

PP270—Computational modeling of dravet syndrome

e102 Volume 35 Number 8S clorazepate (20mg 2× /d), and pregabalin (100 mg 3× /d). Because of resurgence of severe anxio-depressive symptoms, without any change of the treatment, the patient was readmitted 2 months later. Despite increasing the dose of clomipramine up to 225 mg/d, there was no clinical improvement, and the patient finally attempted to her life by abusing drugs. She then improved after 2 weeks on clomipramine IV (50 mg/d). Compliance was estimated good and no pharmacokinetic interactions with the rest of the treatment were found. C and DC plasma levels were measured, and CYP2D6/CYP2C19 genotype analyzed. Results: The plasma levels of C and DC are given in the Table below. Measures were done at the steady state and at trough concentration for IV treatment and 10 hours after the last dose for oral treatment

Molecular phylogeography of the smooth-­‐coated otter (Lutrogale perspicillata, Mustelidae) for its conservation in the Mesopotamian marshes of Iraq

The smooth-coated otter (Lutrogale perspicillata) (SCO) includes perspicillata (SE Asia), sindica (SE Pakistan, W India) and endemic-to-Iraq maxwelli morphological subspecies. Classified as vulnerable by IUCN, the SCO is threatened by habitat transformation, illegal trade and poaching. Non-invasively collected samples in Iraq (10), central and E Asia (nine countries, 46) were sequenced at the entire mtDNA Cytochrome-b gene and genotyped (ongoing) at the microsatellite DNA. We also obtained 307 bp-long gene fragments from 16 SCOs resident to US and European museums. We used 19 Lutrinae GenBank entries. In Iraq, we provided genetic evidence for endemicity of maxwelli to Mesopotamia (private haplotype, mostly from Al-Hawizeh Marsh, S Iraq), while we could not confirm the occurrence of the SCO in N Iraq (Kurdistan).We found reciprocally monophyletic mtDNA lineages across the SCO range each corresponding to a subspecies. Preliminary microsatellite DNA results confirmed this mtDNA picture, overall pointing to three Evolutionarily Significant Units. Looking-like SCOs from Singapore showed oriental small-clawed otter (Aonyx cinerea) mtDNA. We will investigate A. cinerea-mtDNA introgressed SCOs at the microsatellite DNA to assess if they are descendant of L. perspicillata x A. cinerea otters (i.e., first hybrid record in the wild for Lutrinae). Several museum specimens were genetically identified as other than the SCO (even an African otter),indicating that morphology can be not sufficient to reliably catalogue otter study skins. In Iraq, genetic and fieldwork (not shown) data will help establishing a National Single Species Action Plan for the SCO. [National Geographic Society Conservation

Unravelling the biogeography of secretive taxa by museum collections: the untold story of the black francolin (Francolinus francolinus, Phasianidae) in the Mediterranean

The black francolin (Francolinus francolinus) (BF) comprises six morphological subspecies distributed from Cyprus and Turkey across Asia to India. In spite of being renowned as courtly gamebird since the Classic Age, this species suffers from paucity of demographic and molecular studies. In order to update the BF biogeographic pattern by pursuing a thorough sampling across the unsafe and remote areas representing most of the specie’s range, tissues from museum specimens (76, XVIIIth c.-­‐1954) hosted in US and European ornithological collections were genotyped at a 185 bp-­‐long fragment of the mtDNA Control Region gene along with modern birds (205) sequenced at the entire gene. The access to ornithological collections opened the unforeseen opportunity to elucidate the genetic affinity of the extinct populations once residing in the western Mediterranean (Italy, Spain), thus settling the debate about autochthony versus allochthony in that region. Three well-­‐defined haplogroups -­‐ each one including a pair of morphological subspecies and matching the phylogeographical pattern inferred with the whole gene -­‐ were found to reflect a westward adaptive radiation, a more complex scenario being nonetheless disclosed in the Indian sub-­‐continent. The nonnative status of the western Mediterranean BFs was ultimately assessed, a tight genetic affinity with conspecifics from Cyprus and southern Asia being found. This finding, which partly confirmed the invoked importation during the Crusades, pointed to the major human impact on Mediterranean biodiversity through long-­‐distance trade across Asia to satisfy the high demand for exotic species by the European aristocracy during the Medieval times and the Renaissance

Trends in Metal Oxide Stability for Nanorods, Nanotubes, and Surfaces

The formation energies of nanostructures play an important role in determining their properties, including the catalytic activity. For the case of 15 different rutile and 8 different perovskite metal oxides, we find that the density functional theory (DFT) calculated formation energies of (2,2) nanorods, (3,3) nanotubes, and the (110) and (100) surfaces may be described semi-quantitatively by the fraction of metal--oxygen bonds broken and the bonding band centers in the bulk metal oxide

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Dravet syndrome is a rare, treatment-resistant developmental epileptic encephalopathy characterised by multiple types of frequent, disabling seizures. Fenfluramine has been reported to have antiseizure activity in observational studies of photosensitive epilepsy and Dravet syndrome. The aim of the present study was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we enrolled children and young adults with Dravet syndrome. After a 6-week observation period to establish baseline monthly convulsive seizure frequency (MCSF; convulsive seizures were defined as hemiclonic, tonic, clonic, tonic-atonic, generalised tonic-clonic, and focal with clearly observable motor signs), patients were randomly assigned through an interactive web response system in a 1:1:1 ratio to placebo, fenfluramine 0·2 mg/kg per day, or fenfluramine 0·7 mg/kg per day, added to existing antiepileptic agents for 14 weeks. The primary outcome was the change in mean monthly frequency of convulsive seizures during the treatment period compared with baseline in the 0·7 mg/kg per day group versus placebo; 0·2 mg/kg per day versus placebo was assessed as a key secondary outcome. Analysis was by modified intention to treat. Safety analyses included all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov with two identical protocols NCT02682927 and NCT02826863. FINDINGS: Between Jan 15, 2016, and Aug 14, 2017, we assessed 173 patients, of whom 119 patients (mean age 9·0 years, 64 [54%] male) were randomly assigned to receive either fenfluramine 0·2 mg/kg per day (39), fenfluramine 0·7 mg/kg per day (40) or placebo (40). During treatment, the median reduction in seizure frequency was 74·9% in the fenfluramine 0·7 mg/kg group (from median 20·7 seizures per 28 days to 4·7 seizures per 28 days), 42·3% in the fenfluramine 0·2 mg/kg group (from median 17·5 seizures per 28 days to 12·6 per 28 days), and 19·2% in the placebo group (from median 27·3 per 28 days to 22·0 per 28 days). The study met its primary efficacy endpoint, with fenfluramine 0·7 mg/kg per day showing a 62·3% greater reduction in mean MCSF compared with placebo (95% CI 47·7-72·8, p<0·0001); fenfluramine 0·2 mg/kg per day showed a 32·4% reduction in mean MCSF compared with placebo (95% CI 6·2-52·3, p=0·0209). The most common adverse events (occurring in at least 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension. INTERPRETATION: In Dravet syndrome, fenfluramine provided significantly greater reduction in convulsive seizure frequency compared with placebo and was generally well tolerated, with no observed valvular heart disease or pulmonary arterial hypertension. Fenfluramine could be an important new treatment option for patients with Dravet syndrome. FUNDING: Zogenix

19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy

Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, often, this is not feasible. The cell surface and extracellular matrix polysaccharides, glycosaminoglycans (GAGs) lack groups that can be detected selectively in the biological milieu. The introduction of 19F labels into GAG polysaccharides is explored and the interaction of a labelled GAG with the heparin-binding protein, antithrombin, employing 19F NMR spectroscopy is followed. Furthermore, the ability of 19F labelled GAGs to be imaged using CARS microscopy is demonstrated. 19F labelled GAGs enable both 19F NMR protein-GAG binding studies in solution at the molecular level and non-linear microscopy at a microscopic scale to be conducted on the same material, essentially free of background signals

A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

Background: Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS) system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey) were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA) unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey). Results: The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion: In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system