Visual observation of boiling in batch-style water targets

Introduction Batch-style water targets used for F-18 production are known to operate under boiling conditions in the target irradiation chamber, but the distribution of vapor under steady-state conditions was previously unknown. Thermal performance of batch targets has been correlated to average void in the target [1], but the simplified assumptions of such models do not represent the true non-uniform boiling behavior. Visualization targets can be used to observe boiling inside of a target during operation [2–5]. Commercial BTI targets operate at 28–35 bar (400–500 psi) with heat inputs of 0.5 to 3 kW and fill volumes of 1 to 4 mL. Recently, a visualization target featuring two transparent viewing windows was used to observe boiling conditions for realistic operating beam power, target pressure, and fill volume [4]. The same methodology has been applied to three additional visualization targets to examine the effect of target geometry on observed boiling phenomena. Material and Methods The original visualization target featured an aluminum body with a 0.127 mm (0.005 inch) integral aluminum beam window and two viewing windows made of optically clear sapphire (Al2O3). It was operated on an IBA 18/9 cyclotron with 18 MeV protons at beam power up to 1.1 kW, for pressures of 5 to 21 bar (70 to 300 psi), and a fill volume of 2.5 mL. All of the new designs featured a wider chamber to allow for higher beam transmission and an increased chamber height, consistent with cur-rent trends in high power targets. One target featured a reduced chamber depth, and another had a ramp in the back of the chamber to reduce fill volume. Target pressure was limited to a maximum of 14 bar (200 psi) due to the larger diameter beam window. A video camera was used to record the boiling conditions observed for each target under several lighting conditions. During irradiation, the proton beam excites the water molecules, producing visible blue light emissions during de-excitation. These light emissions provide a good indication of beam distribution and penetration depth. A strong backlight can be used to produce clearer images of bubbles generated during boiling. Results and Conclusion Proton range and visible blue light emissions were recorded in dark ambient conditions. The width of the Bragg peak and natural circulation in the bulk fluid were visible with good ambient lighting. Size and distribution of vapor bubbles could be observed by using a strong backlight. The beam current was increased gradually to determine the thermal limit for each target for several fill volumes and pressures. Two thermal limits were observed which resulted in some beam penetration in the top region of the beam. For lower fill volumes, steam ac-cumulates in or around the helium overpressure bubble, causing the helium bubble to move into the upper region of the beam. For higher fill volumes, beam penetration occurs due to excessive voiding, when bubbles produced in the beam region cannot rise quickly enough out of the path of the beam

A Study of The Formation of Stationary Localized States Due to Nonlinear Impurities Using The Discrete Nonlinear Schr\"odinger Equation

The Discrete Nonlinear Schr$\ddot{o}$dinger Equation is used to study the formation of stationary localized states due to a single nonlinear impurity in a Caley tree and a dimeric nonlinear impurity in the one dimensional system. The rotational nonlinear impurity and the impurity of the form $-\chi \mid C \mid^{\sigma}$ where $\sigma$ is arbitrary and $\chi$ is the nonlinearity parameter are considered. Furthermore, $\mid C \mid$ represents the absolute value of the amplitude. Altogether four cases are studies. The usual Greens function approach and the ansatz approach are coherently blended to obtain phase diagrams showing regions of different number of states in the parameter space. Equations of critical lines separating various regions in phase diagrams are derived analytically. For the dimeric problem with the impurity $-\chi \mid C \mid^{\sigma}$, three values of $\mid \chi_{cr} \mid$, namely, $\mid \chi_{cr} \mid = 2$, at $\sigma = 0$ and $\mid \chi_{cr} \mid = 1$ and $\frac{8}{3}$ for $\sigma = 2$ are obtained. Last two values are lower than the existing values. Energy of the states as a function of parameters is also obtained. A model derivation for the impurities is presented. The implication of our results in relation to disordered systems comprising of nonlinear impurities and perfect sites is discussed.Comment: 10 figures available on reques

Aspects of hereditary angioedema genotyping in the era of NGS: The case of F12 gene = Wybrane aspekty genotypowania wrodzonego obrzȩku naczynioruchowego w erze NGS: Gen F12

Objective. To screen a cohort of patients diagnosed with non-FXII angioedema for carriage of variants of F12 gene. Material and methods. DNA samples from 191 patients suffering from primary angioedema with normal C1-INH, 54 samples from non- -affected family members, and 161 samples from C1-INH-HAE (154 type I, 7 type II) patients were included in the study. The F12 gene was genotyped by targeted NGS (100% coverage of translated regions). Sanger sequencing was performed for the verification of all identified variants and family segregation studies. Results. The pathogenic F12 variant c.983C>A was detected in three patients from two unrelated families initially diagnosed as U-HAE. Six additional mutations were identified, four of which were characterized as benign (c.41T>C, c.418C>G, c.1025C>T, c.530C>T) and two of uncertain significance (c.1530G>C, c.1768T>G). Two synonymous variants (c.756C>T and c.711C>T), the common polymorphism c.619G>C, and the functional polymorphism c.-4T>C were detected in allele frequencies similar to those presented in the ExAC database for the European population. One more not yet reported synonymous variant (c. 1599A>G) was also found. Conclusion. Analyzing the entire translated region of F12 gene is important in order to identify new variants that possibly affect HAE expressivity. Interestingly, genetic analysis of F12 supports not only the diagnosis of FXII-HAE but also the correct exclusion diagnosis of U-HAE

Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.

BACKGROUND/METHODS At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with types I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. This article provides recommendations for developing appropriate treatment strategies in the management of HAE-C1-INH in pediatric patients in German-speaking countries. An overview of available drugs in this age group is provided, together with their approval status, and study results obtained in adults and pediatric patients. RESULTS/CONCLUSION Currently, plasma-derived C1 inhibitor concentrates have the broadest approval status and are considered the best available option for on-demand treatment of HAE-C1-INH attacks and for short- and long-term prophylaxis across all pediatric age groups in German-speaking countries. For on-demand treatment of children over 2 years of age, bradykinin-receptor icatibant is an alternative. For long-term prophylaxis in adolescents, the parenteral kallikrein inhibitor lanadelumab has recently been approved and can be recommended due to proven efficacy and safety

design of the HELP study extension

Background Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo- controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. Methods/design The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study (“rollover patients”) and those who did not participate in the double-blind study (“non-rollover patients”), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient’s first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non- rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Discussion Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT0274159

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente