New limits on the 17 keV neutrino

We present results of new measurements of the β spectrum of 35S, using the Caltech double-focusing, iron-free β spectrometer. Our data show no evidence for a heavy neutrino with a mass between 12 and 22 keV admixed to the usual light neutrino. In particular, we rule out, at the 6σ level, a 17 keV neutrino admixed at 0.85%, and give an upper limit (90% C.L.) of 0.2% for such a neutrino admixture. To demonstrate that our experiment is sensitive to spectral features such as those from heavy neutrinos we have induced an artificial kink by means of an absorber foil covering part of the source

Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia

In X-linked hypophosphatemia (XLH), serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi), and inappropriately low normal serum 1,25 dihydroxyvitamin D (1,25[OH]2D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody that binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean ± standard deviation KRN23 doses administered were 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half-life was 16.4 days. The mean area under the concentration–time curve (AUCn) for each dosing interval increased proportionally with increases in KRN23 dose. The mean intersubject variability in AUCn ranged from 30% to 37%. The area under the effect concentration–time curve (AUECn) for change from baseline in TmP per glomerular filtration rate, serum Pi, 1,25(OH)2D, and bone markers for each dosing interval increased linearly with increases in KRN23 AUCn. Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on predose serum Pi concentration

FGF23 is elevated in multiple myeloma and increases heparanase expression by tumor cells

Multiply myeloma (MM) grows in and destroys bone, where osteocytes secrete FGF23, a hormone which affects phosphate homeostasis and aging. We report that multiple myeloma (MM) cells express receptors for and respond to FGF23. FGF23 increased mRNA for EGR1 and its target heparanase, a pro-osteolytic factor in MM. FGF23 signals through a complex of klotho and a classical FGF receptor (FGFR); both were expressed by MM cell lines and patient samples. Bone marrow plasma cells from 42 MM patients stained positively for klotho, while plasma cells from 8 patients with monoclonal gammopathy of undetermined significance (MGUS) and 6 controls were negative. Intact, active FGF23 was increased 2.9X in sera of MM patients compared to controls. FGF23 was not expressed by human MM cells, but co-culture with mouse bone increased its mRNA. The FGFR inhibitor NVP-BGJ398 blocked the heparanase response to FGF23. NVP-BGJ398 did not inhibit 8226 growth in vitro but significantly suppressed growth in bone and induction of the osteoclast regulator RANK ligand, while decreasing heparanase mRNA. The bone microenvironment provides resistance to some anti-tumor drugs but increased the activity of NVP-BGJ398 against 8226 cells. The FGF23/klotho/heparanase signaling axis may offer targets for treatment of MM in bone

Cooperative learning in the first year of undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Despite extensive research data indicating that cooperative learning promotes higher achievement, the creation of positive relationships, and greater psychological health for students at all levels in their education, cooperative learning as a teaching strategy is still underutilized in undergraduate medical education.</p> <p>Methods</p> <p>A cooperative learning task was introduced as part of the mandatory first Year undergraduate Pathology course. The task was to create an 8.5" × 11" poster summary of pre-assigned content in self-chosen groups of four or five students. On the designated "Poster Day," the posters were displayed and evaluated by the students using a group product evaluation. Students also completed an individual group process reflection survey. An objective evaluation of their understanding was gauged at the midterm examination by specific content-related questions.</p> <p>Results</p> <p>Majority (91–96%) of students judged the group products to be relevant, effective, easy-to-understand, and clearly communicated. The majority of the students (90–100%) agreed that their group process skills of time management, task collaboration, decision-making and task execution were effective in completing this exercise. This activity created a dynamic learning environment as was reflected in the students' positive, professional discussion, and evaluation of their posters. The content-related questions on the midterm examination were answered correctly by 70–92% of the students. This was a mutually enriching experience for the instructor and students.</p> <p>Conclusion</p> <p>These findings demonstrate that cooperative learning as a teaching strategy can be effectively incorporated to address both content <it>and </it>interpersonal skill development in the early years of undergraduate medical education.</p

Looking both ways

On the occasion of the 25th anniversary of the journal, Psychotherapy Research, three former editors first look back at: (i) the controversial persistence of the Dodo verdict (i.e., the observation that all bona fide therapies seem equally effective); (ii) the connection between process and outcome; (iii) the move toward methodological pluralism; and (iv) the politicization of the field around evidence-based practice and treatment guidelines. We then look forward to the next 25 years, suggesting that it would be promising to focus on three areas: (i) systematic theory-building research; (ii) renewed attention to fine-grained study of therapist techniques; and (iii) politically expedient research on the outcomes of marginalized or emerging therapies

Lead Slowing-Down Spectrometry for Spent Fuel Assay: FY11 Status Report

Executive Summary Developing a method for the accurate, direct, and independent assay of the fissile isotopes in bulk materials (such as used fuel) from next-generation domestic nuclear fuel cycles is a goal of the Office of Nuclear Energy, Fuel Cycle R&D, Material Protection and Control Technology (MPACT) Campaign. To meet this goal, MPACT supports a multi-institutional collaboration to study the feasibility of Lead Slowing Down Spectroscopy (LSDS). This technique is an active nondestructive assay method that has the potential to provide independent, direct measurement of Pu and U isotopic masses in used fuel with an uncertainty considerably lower than the approximately 10% typical of today’s confirmatory assay methods. This document is a progress report for FY2011 collaboration activities. Progress made by the collaboration in FY2011 continues to indicate the promise of LSDS techniques applied to used fuel. PNNL developed an empirical model based on calibration of the LSDS to responses generated from well-characterized used fuel. The empirical model demonstrated the potential for the direct and independent assay of the sum of the masses of 239Pu and 241Pu to within approximately 3% over a wide used fuel parameter space. Similar results were obtained using a perturbation approach developed by LANL. Benchmark measurements have been successfully conducted at LANL and at RPI using their respective LSDS instruments. The ISU and UNLV collaborative effort is focused on the fabrication and testing of prototype fission chambers lined with ultra-depleted 238U and 232Th, and uranium deposition on a stainless steel disc using spiked U3O8 from room temperature ionic liquid was successful, with improving thickness obtained. In FY2012, the collaboration plans a broad array of activities. PNNL will focus on optimizing its empirical model and minimizing its reliance on calibration data, as well continuing efforts on developing an analytical model. Additional measurements are planned at LANL and RPI. LANL measurements will include a Pu sample, which is expected to provide more counts at longer slowing-down times to help identify discrepancies between experimental data and MCNPX simulations. RPI measurements will include the assay of an entire fresh fuel assembly for the study of self-shielding effects as well as the ability to detect diversion by detecting a missing fuel pin in the fuel assembly. The development of threshold neutron sensors will continue, and UNLV will calibrate existing ultra-depleted uranium deposits at ISU

Circulating FGF21 Levels Are Progressively Increased from the Early to End Stages of Chronic Kidney Diseases and Are Associated with Renal Function in Chinese

Fibroblast growth factor 21 (FGF21) is a hepatic hormone involved in the regulation of lipid and carbohydrate metabolism. This study aims to test the hypothesis that elevated FGF21 concentrations are associated with the change of renal function and the presence of left ventricular hypertrophy (LVH) in the different stages of chronic kidney disease (CKD) progression.0.05).Plasma FGF21 levels are significantly increased with the development of early- to end-stage CKD and are independently associated with renal function and adverse lipid profiles in Chinese population. Understanding whether increased FGF21 is associated with myocardial hypertrophy in CKD requires further study