A
bstract
In spring 2012 CERN provided two weeks of a short bunch proton beam dedicated to the neutrino velocity measurement over a distance of 730 km. The OPERA neutrino experiment at the ...underground Gran Sasso Laboratory used an upgraded setup compared to the 2011 measurements, improving the measurement time accuracy. An independent timing system based on the Resistive Plate Chambers was exploited providing a time accuracy of ~1 ns. Neutrino and anti-neutrino contributions were separated using the information provided by the OPERA magnetic spectrometers. The new analysis profited from the precision geodesy measurements of the neutrino baseline and of the CNGS/LNGS clock synchronization. The neutrino arrival time with respect to the one computed assuming the speed of light in vacuum is found to be δ
t
ν
≡
T OF
c
−
T OF
ν
= (0.6±0.4 (
stat
.)±3.0 (
syst
.)) ns and
ns for ν
μ
and
, respectively. This corresponds to a limit on the muon neutrino velocity with respect to the speed of light of −1.8 × 10
−6
< (
v
ν
−
c
)/
c
< 2.3 × 10
−6
at 90% C.L. This new measurement confirms with higher accuracy the revised OPERA result.
The OPERA neutrino experiment in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in direct appearance mode in the νμ → ντ channel, ...the ντ signature being the identification of the τ-lepton created in its charged current interaction. The hybrid apparatus consists of a large mass emulsion film lead target complemented by electronic detectors. Placed in the LNGS, it is exposed to the high-energy long-baseline CERN Neutrino beam to Gran Sasso (CNGS) 730 km away from the neutrino source. The observation of a first ντ candidate event was reported in 2010. In this paper, we discuss the result of the analysis of the data taken during the first two years of operation (2008-2009) underlining the major improvements brought to the analysis chain and to the Monte Carlo simulations. The statistical significance of the one event observed so far is then evaluated to 95%.
The Lebedev Physical Institute of the Russian Academy of Sciences and the Skobeltsyn Institute of Nuclear Physics of Moscow State University conduct experiments using nuclear photoemulsion to study ...the internal structure of large objects via muon radiography. Analysis of an experiment in a mine in Obninsk belonging to the Geophysical Service of the Russian Academy of Sciences is of particular interest. Calculated and experimental data are presented.
CdK EXAFS, ZnK and CuK EXAFS and XANES spectra were measured for solutions of cadmium, zinc and copper dialkyldithiocarbamates in organic solvents with varying donating abilities: tributylphosphine, ...methylene chloride, benzene, dibutylsulfide, pyridine, dimethylsulfoxide and for some model compounds. The parameters of the local surroundings of the Cd, Zn and Cu atoms for complex forms in solutions were determined using EXAFS spectroscopy. Spatial structure models of the complex forms in a metal chelate – nonaqueous solvent system are suggested.
The OPERA neutrino experiment is designed to perform the first observation of neutrino oscillations in direct appearance mode in the $\nu_\mu \to \nu_\tau$ channel, via the detection of the ...$\tau$-leptons created in charged current $\nu_\tau$ interactions. The detector, located in the underground Gran Sasso Laboratory, consists of an emulsion/lead target with an average mass of about 1.2 kt, complemented by electronic detectors. It is exposed to the CERN Neutrinos to Gran Sasso beam, with a baseline of 730 km and a mean energy of 17 GeV. The observation of the first $\nu_\tau$ candidate event and the analysis of the 2008-2009 neutrino sample have been reported in previous publications. This work describes substantial improvements in the analysis and in the evaluation of the detection efficiencies and backgrounds using new simulation tools. The analysis is extended to a sub-sample of 2010 and 2011 data, resulting from an electronic detector-based pre-selection, in which an additional $\nu_\tau$ candidate has been observed. The significance of the two events in terms of a $\nu_\mu \to \nu_\tau$ oscillation signal is of 2.40 $\sigma$.
Crystalline structure and phase composition of thin CdS, Cu
2S and Cd(Cu)S films were investigated using diffraction of synchrotron radiation (SR). These films were synthesized by RPECVD using ...nontraditional volatile sulphur-containing precursors. The diffraction measurements were performed at the station “Anomalous Scattering”, existed at the second canal of colliding electron–positron beam accelerator VEPP-3 of Siberian center of SR (Institute of Nuclear Physics of SB RAS, Novosibirsk, Russia). It was established that these films have a high transmittance in the visible range of spectra. This type of substrate material was found to determine the structure of sulphide films. The deviation of lattice parameters of cadmium and copper sulphides in thin film state obtained on Si(1
0
0) substrates from following the parameters in bulk state probably connects with lattice mismatch of silicon substrate and hexagonal structure of growing sulphide films.
In Russia, the Lebedev Physical Institute of the Russian Academy of Sciences and the Skobeltsyn Institute of Nuclear Physics of Moscow State University are starting a series of pilot muon radiography ...exper-iments with nuclear emulsion detectors to study the interior structure of large-scale natural and industrial objects. As a result, the optimal conditions for experimental organization have been determined, algorithms of data processing have been worked out, and peculiarities of the method have been ultimately investigated. Here we present the experimental data, including field observations (in the mine of Geophysical department of Russian Academy of Sciences) confirming the availability of the method with track detectors on the base of nuclear emulsions with uniquely high spatial resolution, providing their high-tech automated processing.
Abstract
Disclosure: S. Jhawar: None. S. Jumani: None. Y. Sterrett: None. H. Elenius: None. P. Veeraraghavan: None. C. Ryan: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. J.G. ...Verbalis: None. L.K. Nieman: None. E. Globa: None. M.S. Zemskova: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None.
Introduction: Nephrogenic diabetes insipidus (NDI) is commonly associated with the use of medications such as lithium, antibiotics, and chemotherapeutic agents or with renal disorders. Rarely, NDI can be a manifestation of paraneoplastic conditions. We describe a case of NDI caused by severe hypokalemia in a patient with metastatic medullary thyroid cancer (MTC) and paraneoplastic Cushing’s syndrome (CS). Clinical Case: A 47-year-old male with sporadic, metastatic MTC (RET M918T pathogenic variant) was referred to our institution for further management. The patient had florid metastases to the liver, lungs, and skeleton, with a calcitonin of 158,535 pg/mL normal (NL): <14.3, and a CEA of 3,634 pg/mL (NL: 0.8-3.4), but surprisingly, without an intrathyroidal primary tumor. Vandetanib and octreotide were previously trialed but discontinued due to financial constraints. The patient had diarrhea, but no other symptoms. Physical exam revealed cervical lymphadenopathy, facial plethora, dorsocervical fat pad, and a single purple stria on the chest. Further work up revealed markedly elevated 24-hr urine free cortisol (12,460 mcg/24hr; NL: 35-45), ACTH 116 pg/mL (normal 5.0-46.0), and an undetectable serum aldosterone and plasma renin activity, raising suspicion for paraneoplastic ectopic-CS. Immunostaining of the MTC biopsy specimen showed ACTH positivity. During the inpatient admission, polyuria of >3L/day was noted on two consecutive 24-hour urine measurements. Laboratory investigations revealed hypernatremia (serum sodium: 147 mmol/L; NL: 136-145), elevated serum osmolality (303 mOsm/Kg; NL: 278-298), and a low urine osmolality (215 mOsm/kg; NL: 300-900), thus establishing the diagnosis of DI. A simultaneous, elevated plasma copeptin (36.3 pmol/L; NL: <13.1) further suggested NDI. Also noted was severe hypokalemia (serum potassium: 1.7 mmol/L; NL: 3.5-5.1), with normal serum magnesium and calcium. A thorough review of patient’s medication list did not reveal any culprit drug for hypokalemia or NDI. Hypokalemia was managed with aggressive oral and intravenous potassium repletion. A bilateral adrenalectomy was performed to treat the ectopic-CS, which improved the hypokalemia and resolved the NDI. Three months later, the patient unfortunately died due to progression of MTC. Conclusion: Severe hypokalemia causes autophagic degradation of aquaporin-2 channels in the renal tubules and is an under-recognized cause of NDI. Profound hypercortisolism in ectopic-CS may result in cortisol-mediated overactivation of mineralocorticoid receptors that can cause renal potassium loss leading to NDI. Only 0.6% of MTCs are associated with ectopic-CS (PMID: 16029131). Our report highlights hypokalemia-induced NDI as a manifestation of paraneoplastic CS resulting from MTC.
Presentation: Friday, June 16, 2023
Abstract
Insulin-like growth factor-1 (IGF-1) is a key hormone in mediating the physiological response to endogenous and exogenous growth hormone (GH). Current clinical guidelines suggest use of ...IGF-1 for dose titration in adults with GH deficiency and for safety monitoring in adults and pediatric patients. Several GH drug development programs for pediatric indications have collected IGF-1, height standard deviation score (HSDS), and height velocity (HV), to support dose selection in Phase 3 clinical trials. In this analysis, patients born small for gestational age (SGA) who fail to demonstrate catch-up growth by age 2–4 years from different growth hormone product development programs were included. A total of 663 patients from 8 clinical trials were included in this analysis, with 7 placebo arms and 15 growth hormone treated arms. The growth hormone dosing regimen ranged from 33 ug/kg/day to 100 ug/kg/day. Both boys and girls throughout a wide range of ages (3 to 7 years old on average) were represented in this analysis. The average patient was 3 to 4 standard deviations below the age- and sex- adjusted mean height at baseline. IGF-1 was collected and standardized according to age and sex, so called the IGF-1 standard deviation score (IGF-1 SDS). At baseline, the average patient had normal IGF-1 (-1 to 0 on average). Based on preliminary findings, IGF-1 SDS change from baseline (CFB) at 6 months was correlated with HSDS CFB at 12 months. HSDS CFB at 3 months and 6 months were also correlated with HSDS CFB at 12 months, respectively. These findings were consistent across the three GH products included in the analysis, as well as age and gender. However, IGF-1 SDS CFB had much larger variability than HSDS CFB. Both HSDS CFB at 3 months and 6 months precisely and accurately predicted HSDS CFB at 12 months. IGF-1 SDS was more variable and did not add any further contribution in the prediction of HSDS at 12 months and therefore IGF-1 may not be sufficient in informing Phase 3 dose selection in such trials.
Reference: 1. Shoshana Yakar, Clifford J. Rosen, Wesley G. Beamer, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002 Sep 15; 110(6): 771–781. 2. Locatelli V, Bianchi VE. Effect of GH/IGF-1 on Bone Metabolism and Osteoporosis. Int J Endocrinol. 2014;2014:235060 Nothing to Disclose: TL, JP, BC, MZ, JV, CS
PDF
