Measurement of the Isolated Nuclear Two-Photon Decay in

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100 keV and half-lives as short as ∼10 ms. The half-life for the 2γ decay of the first-excited 0^{+} state in bare ^{72}Ge ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

The development and validation of the secondary exercise addiction scale.

OBJECTIVES: Exercise addiction can be secondary to eating disorders, or a primary condition in the absence of another disorder. Currently, to determine secondary exercise addiction, two screening tools must be administered. The aim of this study was to validate a novel screening tool able to stratify between primary and secondary exercise addiction, called the secondary exercise addiction scale (SEAS). METHODS: Phase 1 (n = 339) described the statistical reduction of an initial pool of scale items. Phase 2 (n = 382) used a confirmatory factor analysis (CFA) to examine the robustness of the latent structure. Phase 3 (n = 721) determined cut off scores for the eating disorder and exercise addiction sections of the SEAS and determine concurrent reliability with the exercise addiction inventory (EAI) and the SCOFF questionnaires. Phase 4 (n = 45) determined test-retest reliability. RESULTS: Phase 1 extracted two components: exercise addiction and eating disorder symptomology, with 11 items retained. The CFA in Phase 2 showed an acceptable fit to the proposed model (comparative fit index = 0.93, Tucker Lewis Index = 0.91). Phase 3 determined cut off scores of ≥ 28 (specificity = 91.97%), and ≥ 20 (specificity = 96.27%) in the respective exercise addiction and eating disorders sections of the SEAS. The respective sections also correlated well with the EAI (r = 0.70, p = < 0.001) and the SCOFF (r = 0.72, p = < 0.001). Phase 4 showed excellent test-retest reliability (exercise addiction r = 0.95, p = < 0.001, eating disorders r = 0.93, p = < 0.001). CONCLUSION: The SEAS appears to be a valid and reliable tool for measuring primary and secondary exercise addiction. Further studies are warranted to further validate this tool amongst clinical populations. LEVEL OF EVIDENCE: Level III: evidence obtained from cohort or case-control analytic studies.

Spectroscopy along Flerovium Decay Chains: Discovery of

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

Search for Electron-Capture Delayed Fission in the New Isotope

The electron-capture decay followed by a prompt fission process was searched for in the hitherto unknown most neutron-deficient Md isotope with mass number 244. Alpha decay with α-particle energies of 8.73-8.86 MeV and with a half-life of 0.30_{-0.09}^{+0.19} s was assigned to ^{244}Md. No fission event with a similar half-life potentially originating from spontaneous fissioning of the short-lived electron-capture decay daughter ^{244}Fm was observed, which results in an upper limit of 0.14 for the electron-capture branching of ^{244}Md. Two groups of fission events with half-lives of 0.9_{-0.3}^{+0.6} ms and 5_{-2}^{+3} ms were observed. The 0.9_{-0.3}^{+0.6} ms activity was assigned to originate from the decay of ^{245}Md. The origin of eight fission events resulting in a half-life of 5_{-2}^{+3} ms could not be unambiguously identified within the present data while the possible explanation has to invoke previously unseen physics cases.

Precision Measurement of the First Ionization Potential of Nobelium.

One of the most important atomic properties governing an element's chemical behavior is the energy required to remove its least-bound electron, referred to as the first ionization potential. For the heaviest elements, this fundamental quantity is strongly influenced by relativistic effects which lead to unique chemical properties. Laser spectroscopy on an atom-at-a-time scale was developed and applied to probe the optical spectrum of neutral nobelium near the ionization threshold. The first ionization potential of nobelium is determined here with a very high precision from the convergence of measured Rydberg series to be 6.626 21±0.000 05 eV. This work provides a stringent benchmark for state-of-the-art many-body atomic modeling that considers relativistic and quantum electrodynamic effects and paves the way for high-precision measurements of atomic properties of elements only available from heavy-ion accelerator facilities.

Probing Sizes and Shapes of Nobelium Isotopes by Laser Spectroscopy.

Until recently, ground-state nuclear moments of the heaviest nuclei could only be inferred from nuclear spectroscopy, where model assumptions are required. Laser spectroscopy in combination with modern atomic structure calculations is now able to probe these moments directly, in a comprehensive and nuclear-model-independent way. Here we report on unique access to the differential mean-square charge radii of ^{252,253,254}No, and therefore to changes in nuclear size and shape. State-of-the-art nuclear density functional calculations describe well the changes in nuclear charge radii in the region of the heavy actinides, indicating an appreciable central depression in the deformed proton density distribution in ^{252,254}No isotopes. Finally, the hyperfine splitting of ^{253}No was evaluated, enabling a complementary measure of its (quadrupole) deformation, as well as an insight into the neutron single-particle wave function via the nuclear spin and magnetic moment.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

Spectroscopy of element 115 decay chains.

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

On the adsorption and reactivity of element 114, flerovium.

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

MRI of asymptomatic patients with metal-on-metal and polyethylene-on-metal total hip arthroplasties.

AIMS: To define and compare magnetic resonance imaging (MRI) findings of asymptomatic patients with metal-on-metal (MOM) and polyethylene-on-metal (POM) total hip replacements (THRs). MATERIALS AND METHODS: Twenty-two THRs in 20 asymptomatic patients (seven men, 13 women, mean age 68 years, range 47-86 years) with normal hip radiographs were included in the study. These comprised 10 POM and 12 MOM bearings. Each patient underwent MRI with metal artefact reduction sequences (MARS) at a mean time of 46 months (POM) and 70 months (MOM) after surgery. Two musculoskeletal radiologists independently read each MRI examination for fluid collections, soft-tissue masses, muscle atrophy, and bone marrow signal changes. RESULTS: A pre-MRI hip radiograph showed no significant differences from the postoperative radiograph regarding acetabular inclination, femoral stem angle, and stem mantle grade. There were eight periprosthetic collections (one POM, seven MOM). The majority of THRs had normal gluteal muscles. The ipsilateral piriformis and obturator internus muscles were more frequently abnormal in the MOM group. Overall, there were no significant differences in the number of abnormalities between the two types of bearings. CONCLUSION: A range of MRI abnormalities are present in normal asymptomatic THRs but the increased frequency of these associated with MOM THR suggest that some of these changes might represent subclinical disease.

Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate - A report of two cases.

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 µg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

First Study on Nihonium (Nh, Element 113) Chemistry at TASCA.

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

White Matter Disease and Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear. MATERIALS AND METHODS: In this prespecified exploratory analysis of our prospective multi-institutional study that enrolled consecutive adult patients with anterior circulation ischemic stroke undergoing endovascular treatment from November 2017 to September 2018, we compared the following outcomes between patients with none-to-minimal (van Swieten score, 0-2) and moderate-to-severe (van Swieten score, 3-4) white matter disease using logistic regression: 90-day mRS 3-6, death, intracerebral hemorrhage, successful recanalization, and early neurologic recovery. RESULTS: Of the 485 patients enrolled in the Blood Pressure after Endovascular Stroke Therapy (BEST) study, 389 had white matter disease graded (50% women; median age, 68 years; range, 58-79 years). A van Swieten score of 3-4 (n = 74/389, 19%) was associated with a higher rate of 90-day mRS of 3-6 (45% versus 18%; adjusted OR, 2.73; 95% CI, 1.34-5.93; P = .008). Although the death rate was higher in patients with van Swieten scores of 3-4 (26% versus 15%), the adjusted likelihood was not significantly different (adjusted OR, 1.14; 95% CI, 0.56-2.26; P = .710). Ordered regression revealed a shift toward worse mRS scores with increasing van Swieten scores (adjusted common OR, 3.04; 95% CI, 1.93-4.84; P < .001). No associations between white matter disease severity and intracerebral hemorrhage, successful recanalization, and early neurologic recovery were observed. CONCLUSIONS: Moderate-to-severe white matter disease is associated with worse outcomes in patients undergoing endovascular treatment without a significant increase in hemorrhagic complications. Studies comparing patients with and without endovascular treatment are necessary to determine whether the benefit of endovascular treatment is attenuated with greater white matter disease.

Ascertaining the epidemiology, patient flow and disease management for Dravet syndrome in Spain. / Determinacion de la epidemiologia, el flujo de pacientes y el tratamiento del sindrome de Dravet en España.

INTRODUCTION: Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types. AIM: To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts. DEVELOPMENT: A two-round Delphi study involving 19 physicians was conducted. Questionnaires were based on literature review and validated by clinical experts. Consensus was reached when topics were subject to routine clinical practice and individual experience, or the coefficient of variation among answers was <= 0.3. The estimated number of new DS patients is 73 per year. Prevalence is estimated to be between 348-540 patients. DS is mostly diagnosed in children. Survival varies from 5 to 60 years. There is no standardised follow-up of patients beyond the age of 18 and mortality rates are uncertain. No standard guidelines exist for diagnosing or treating DS. It takes 9 to 15 months to confirm the diagnosis and genetic testing is unevenly available. Valproic acid, clobazam, stiripentol and topiramate are commonly used. Poor efficacy and safety are the main reasons for treatment switch. CONCLUSIONS: The epidemiology of DS in Spain is not well known and several areas of unmet needs still exist. Experts' views offer a starting point for further research into the reality of DS in Spain. Epidemiological studies, consensus criteria, easy access to genetic testing, treatment options, training and research into quality of life aspects are highly needed.

TITLE: Determinacion de la epidemiologia, el flujo de pacientes y el tratamiento del sindrome de Dravet en España.Introduccion. El sindrome de Dravet (SD) es una epilepsia rara y resistente a los farmacos que comienza en etapas muy precoces de la vida con convulsiones febriles, seguidas de deterioro cognitivo y diversos tipos de crisis epilepticas. Objetivo. Generar datos objetivos sobre la epidemiologia del SD, su diagnostico, el flujo de pacientes, el tratamiento y las necesidades no cubiertas desde el punto de vista de expertos españoles. Desarrollo. Se efectuo un estudio Delphi de dos rondas en el que participaron 19 medicos. Los cuestionarios se basaron en una revision de la bibliografia y fueron validados por expertos clinicos. Se alcanzo consenso si los temas se referian a la practica clinica habitual y la experiencia individual, o si el coeficiente de variacion entre las respuestas era <= 0,3. El numero estimado de pacientes nuevos con SD es de 73 al año. La prevalencia se calcula entre 348 y 540 pacientes. El SD se diagnostica principalmente en niños. La supervivencia varia entre los 5 y los 60 años. No existe ningun seguimiento normalizado para los pacientes de mas de 18 años de edad, y las tasas de mortalidad son inciertas. No existen guias normalizadas para diagnosticar o tratar el SD. Se tarda de 9 a 15 meses en confirmar el diagnostico, y la disponibilidad de los analisis geneticos es irregular. Normalmente se utilizan el acido valproico, el clobazam, el estiripentol y el topiramato. La escasa eficacia y la seguridad son los motivos principales de los cambios de tratamiento. Conclusiones. La epidemiologia del SD en España es poco conocida, y sigue habiendo necesidades no cubiertas en algunas areas. Las opiniones de expertos suponen un punto de partida para poder investigar la realidad del SD en España. Los estudios epidemiologicos, los criterios de consenso, el acceso facil a las pruebas geneticas, las opciones de tratamiento, la formacion y la investigacion de la calidad de vida relacionada con la salud constituyen todos ellos aspectos muy necesarios.

Degradation and biocompatibility of a poly(propylene fumarate)-based/alumoxane nanocomposite for bone tissue engineering.

In this work, we evaluated the in vitro cytotoxicity and in vivo biocompatibility of a novel poly(propylene fumarate) (PPF)-based/alumoxane nanocomposite for bone tissue engineering applications. The incorporation of functionalized alumoxane nanoparticles into the PPF-based polymer was previously shown to significantly increase the material's flexural mechanical properties. In the current study, samples underwent accelerated in vitro degradation to allow the study of biological responses to these materials over the course of their degradation on a shortened timescale. The polymer, a macrocomposite composed of the polymer and micron-sized particles, and the nanocomposite were evaluated at three stages of degradation for in vitro cytotoxicity with a fibroblast cell line and in vivo soft-tissue response after 3 and 12 weeks of implantation in adult goats. All three material groups experienced mass loss during degradation, but the nanocomposite group eroded significantly faster than the other groups. Nondegraded materials demonstrated minimal cytotoxicity and a minor inflammatory response in soft tissue. On the contrary, predegraded samples elicited more pronounced responses, though these were due to the increase in surface area, surface roughness, and fragmentation associated with the degradation process. The presence of alumoxane nanoparticles in the PPF-based nanocomposite did not significantly affect its cytotoxicity or biocompatibility.

Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin.

BACKGROUND: UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyses the first committed step of bacterial cell wall biosynthesis and is a target for the antibiotic fosfomycin. The only other known enolpyruvyl transferase is 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, an enzyme involved in the shikimic acid pathway and the target for the herbicide glyphosate. Inhibitors of enolpyruvyl transferases are of biotechnological interest as MurA and EPSP synthase are found exclusively in plants and microbes. RESULTS: The crystal structure of Escherichia coli MurA complexed with UDP-N-acetylglucosamine (UDP-GlcNAc) and fosfomycin has been determined at 1.8 A resolution. The structure consists of two domains with the active site located between them. The domains have a very similar secondary structure, and the overall protein architecture is similar to that of EPSP synthase. The fosfomycin molecule is covalently bound to the cysteine residue Cys115, whereas UDP-GlcNAc makes several hydrogen-bonding interactions with residues from both domains. CONCLUSIONS: The present structure reveals the mode of binding of the natural substrate UDP-GlcNAc and of the drug fosfomycin, and provides information on the residues involved in catalysis. These results should aid the design of inhibitors which would interfere with enzyme-catalyzed reactions in the early stage of the bacterial cell wall biosynthesis. Furthermore, the crystal structure of MurA provides a model for predicting active-site residues in EPSP synthase that may be involved in catalysis and substrate binding.

Calcium ions as efficient cofactor of polycation-mediated gene transfer.

We investigated the effect of calcium on the transfection of non-viral DNA transfer systems. Cationic proteins such as the nuclear protein H1, the polycation polylysine and a number of commercial transfection agents exhibited high transfection rates in the presence of Ca2+. Without Ca2+ H1 and HMG1 were inactive in transfection of the human permanent endothelial cell line ECV 304 while cationic liposomes such as Lipofectin and Lipofectamine did not show any Ca2+ dependence. More detailed experiments showed that Ca2+ was replaceable by the lysosomotropic agent chloroquine. Furthermore, it was possible to separate the transfection-enhancing role of Ca2+ from the actual transfection process by adding Ca2+ to the cells after the transfection period and still to obtain a significant transgene expression. This makes it possible to distinguish between cellular uptake of H1 (or mediator)-DNA complexes and endocytotic release. We also replaced soluble Ca2+ by Ca-phosphate precipitates not containing DNA and obtained similar transfection results. This allowed us to suggest that the addition of free Ca2+ to the transfection medium resulted in nascent Ca-phosphate microprecipitates. The known fusogenic and membranolytic activity of such microprecipitates could facilitate the transport through and the release of the transfecting complexes from the endosomal/lysosomal compartment.

Crystallization and preliminary diffraction studies of Erythrina trypsin inhibitor.

Crystals of an inhibitor of trypsin and tissue plasminogen activator from seeds of the legume Erythrina caffra have been obtained by vapour diffusion. The crystals belong to the hexagonal space group P6(1)22 (or its enantiomorph P6(5)22) with cell parameters 73.4 A and 143.0 A. There is one molecule in the asymmetric unit. The crystals diffract to beyond 2.5 A resolution.