Searching for dark matter with plasma haloscopes

We summarize the recent progress of the Axion Longitudinal Plasma Haloscope (ALPHA) Consortium, a new experimental collaboration to build a plasma haloscope to search for axions and dark photons. The plasma haloscope is a novel method for the detection of the resonant conversion of light dark matter to photons. ALPHA will be sensitive to QCD axions over almost a decade of parameter space, potentially discovering dark matter and resolving the strong CP problem. Unlike traditional cavity haloscopes, which are generally limited in volume by the Compton wavelength of the dark matter, plasma haloscopes use a wire metamaterial to create a tuneable artificial plasma frequency, decoupling the wavelength of light from the Compton wavelength and allowing for much stronger signals. We develop the theoretical foundations of plasma haloscopes and discuss recent experimental progress. Finally, we outline a baseline design for ALPHA and show that a full-scale experiment could discover QCD axions over almost a decade of parameter space

Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial

<p>Abstract</p> <p>Background</p> <p>Conventional antipsychotics augmented with benzodiazepines have been the standard acute treatment for psychiatric emergencies for more than 50 years. The inability of patients to give informed consent limits randomised, controlled studies. This observational study on immediate therapy for aggression and impulse control in acutely agitated patients (IMPULSE) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications (AP) in a non-interventional setting.</p> <p>Methods</p> <p>This was a comparative, non-randomised, prospective, open-label, observational study. Treatment over the first 5 days was classified according to whether any olanzapine, risperidone, or haloperidol was included or not. Documentations (PANSS-excited component, CGI-aggression, CGI-suicidality, tranquilisation score) were at baseline (day 1) and days 2–6 after start of AP.</p> <p>Results</p> <p>During the short treatment-period, PANSS-EC and CGI-aggression scores improved in all cohorts. 68.7% of patients treated with olanzapine, 72.2% of patients treated with risperidone, and 83.3% of patients treated with haloperidol received concomitant benzodiazepines (haloperidol vs. non-haloperidol: p < 0.001). More patients treated with olanzapine (73.8%) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone (57.1%) or haloperidol (58.0%).</p> <p>Conclusion</p> <p>Current medication practices for immediate aggression control are effective with positive results present within a few days. In this study, concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol.</p

Mass Measurements of Neutron-Deficient Yb Isotopes and Nuclear Structure at the Extreme Proton-Rich Side of the N=82 Shell

International audienceHigh-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITAN’s multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of Yb150,153 and the excitation energy of Ybm151 were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h11/2-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculation

Search for Neutrinoless Double- β Decay with the Complete EXO-200 Dataset

A search for neutrinoless double-β decay (0νββ) in Xe136 is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νββ and background events. Relative to previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of Xe136 0νββ has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νββ half-life sensitivity for this analysis is 5.0×1025 yr with a total Xe136 exposure of 234.1 kg yr. No statistically significant evidence for 0νββ is observed, leading to a lower limit on the 0νββ half-life of 3.5×1025 yr at the 90% confidence level

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

Noninvasive 89Zr-Transferrin PET Shows Improved Tumor Targeting Compared with 18F-FDG PET in MYC-Overexpressing Human Triple-Negative Breast Cancer

The current standard for breast PET imaging is 18F-FDG. The heterogeneity of 18F-FDG uptake in breast cancer limits its utility, varying greatly among receptor status, histopathologic subtypes, and proliferation markers. 18F-FDG PET often exhibits nonspecific internalization and low specificity and sensitivity, especially with tumors smaller than 1 cm3 MYC is a protein involved in oncogenesis and is overexpressed in triple-negative breast cancer (TNBC). Increased surface expression of transferrin receptor (TfR) is a downstream event of MYC upregulation and has been validated as a clinically relevant target for molecular imaging. Transferrin labeled with 89Zr has successfully identified MYC status in many cancer subtypes preclinically and been shown to predict response and changes in oncogene status via treatment with small-molecule inhibitors that target MYC and PI3K signaling pathways. We hypothesized that 89Zr-transferrin PET will noninvasively detect MYC and TfR and improve upon the current standard of 18F-FDG PET for MYC-overexpressing TNBC. Methods: In this study, 89Zr-transferrin and 18F-FDG imaging were compared in preclinical models of TNBC. TNBC cells (MDA-MB-157, MDA-MB-231, and Hs578T) were treated with bromodomain-containing protein 4 (BRD4) inhibitors JQ1 and OTX015 (0.5-1 μM). Cell proliferation, gene expression, and protein expression were assayed to explore the effects of these inhibitors on MYC and TfR. Results: Head-to-head comparison showed that 89Zr-transferrin targets TNBC tumors significantly better (P &lt; 0.05-0.001) than 18F-FDG through PET imaging and biodistribution studies in MDA-MB-231 and MDA-MB-157 xenografts and a patient-derived xenograft model of TNBC. c-Myc and TfR gene expression was decreased upon treatment with BRD4 inhibitors and c-MYC small interfering RNA (P &lt; 0.01-0.001 for responding cell lines), compared with vehicle treatment. MYC and TfR protein expression, along with receptor-mediated internalization of transferrin, was also significantly decreased upon drug treatment in MDA-MB-231 and MDA-MB-157 cells (P &lt; 0.01-0.001). Conclusion:89Zr-transferrin targets human TNBC primary tumors significantly better than 18F-FDG, as shown through PET imaging and biodistribution studies. 89Zr-transferrin is a useful tool to interrogate MYC via TfR-targeted PET imaging in TNBC

Star polymers for PET/MRI : a passive pretargeting approach

Objectives: The pretargeting approach, in which a targeting ligand is allowed to accumulate at the target site before a small effector molecule is injected, has successfully been applied to enhance specificity and reduce off-target radiation dose in positron emission tomography (PET) imaging and radioimmunotherapy. To enable accumulation at the target site without the need to rely on receptor availability, passive targeting may be preferred. Nanoparticles may utilize the enhanced permeability and retention (EPR) effect that is often associated with solid tumors. Not only will such nanoparticles exploit the advantages of pretargeting, they also profit from the increased availability of binding sites for the radiolabeled effector, as well as allow for multimodality imaging, combining PET with magnetic resonance imaging (MRI). Methods: Via RAFT polymerization, a star-shaped copolymer was synthesized, consisting of oligoethylene glycol methyl ether acrylate (OEGA) units, 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) units modified with [Gd3+]1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid)-10-(aminoethylacetamide) ([Gd3+]DO3A) and aminoethyl acrylate (AEA) units modified with either deferoxamine (DFO) or trans-cyclooctene (TCO). The DFO-conjugated star polymer was radiolabeled with 89Zr, whereas the TCO-conjugated star polymer was used for pretargeting with [18F]F-tetrazine-poly(ethylene glycol)11-1,4,7-triazacyclononane-1,4-diacetic acid ([18F]F-Tz-PEG11-NODA).1 Biodistribution and bioorthogonal ligation will be assessed in athymic nude mice carrying subcutaneous BxPC3 xenografts. 1H longitudinal relaxivities were determined over a continuum of magnetic field strengths ranging from 0.24 mT - 0.94 T at 37 °C (nuclear magnetic relaxation dispersion (NMRD) profile). RESULTS: The star polymer (84 kDa, PDI = 1.16, Dh = 11 nm) consisted of 7 to 8 cross-linked polymer arms, each containing approximately 19×OEGA repeat units, 5×VDM-[Gd3+]DO3A units and 4×AEA-DFO or AEA-TCO units. Radiolabeling of the star polymer with 89Zr was achieved with high radiochemical yield (>99%) and purity (>99%) and high molar activity (>290 GBq µmol-1). Accumulation of the star polymers in BxPC3 xenografts and bioorthogonal click efficiency will be discussed. The NMRD profile was typical of a paramagnetic nanoparticle, with maximal relaxivity (16.9 mM-1s-1) at ~30 MHz. CONCLUSIONS: Star-shaped nanoparticles were developed in which passive pretargeting PET imaging is combined with MRI. Such nanoparticles minimize the radiation dose to healthy tissues, while offering increased sensitivity and specificity as well as improved tissue contrast