What is the Potential Impact of the IsoDAR Cyclotron on Radioisotope Production: A Review

The IsoDAR collaboration is developing a high-current cyclotron for a neutrino search experiment. Designed to deliver 10 mA of 60 MeV protons, the current and power of this cyclotron far exceed those of existing accelerators, opening new possibilities for the production of radiopharmaceutical isotopes, producing very high-activity samples in very short times. The cyclotron can also be easily configured to deliver ions other than protons including 1 mA of alpha particles at 240 MeV: this flexibility gives a broad reach into new areas of isotope production. We explain how IsoDAR overcomes the beam limits of commercial cyclotrons, and how it could represent the next step in isotope production rates.Comment: 23 pages, 7 figures, manuscript submitted to European Journal of Nuclear Medicin

Medical Isotope Production with the IsoDAR Cyclotron

Authors describe technical advances that will allow the IsoDAR cyclotron -- being developed for neutrino physics research -- to produce medical isotopes more efficiently than existing cyclotrons can.Comment: 3 pages 1 tabl

Modelling the balance of care:Impact of an evidence-informed policy on a mental health ecosystem

Major efforts worldwide have been made to provide balanced Mental Health (MH) care. Any integrated MH ecosystem includes hospital and community-based care, highlighting the role of outpatient care in reducing relapses and readmissions. This study aimed (i) to identify potential expert-based causal relationships between inpatient and outpatient care variables, (ii) to assess them by using statistical procedures, and finally (iii) to assess the potential impact of a specific policy enhancing the MH care balance on real ecosystem performance. Causal relationships (Bayesian network) between inpatient and outpatient care variables were defined by expert knowledge and confirmed by using multivariate linear regression (generalized least squares). Based on the Bayesian network and regression results, a decision support system that combines data envelopment analysis, Monte Carlo simulation and fuzzy inference was used to assess the potential impact of the designed policy. As expected, there were strong statistical relationships between outpatient and inpatient care variables, which preliminarily confirmed their potential and a priori causal nature. The global impact of the proposed policy on the ecosystem was positive in terms of efficiency assessment, stability and entropy. To the best of our knowledge, this is the first study that formalized expert-based causal relationships between inpatient and outpatient care variables. These relationships, structured by a Bayesian network, can be used for designing evidence-informed policies trying to balance MH care provision. By integrating causal models and statistical analysis, decision support systems are useful tools to support evidence-informed planning and decision making, as they allow us to predict the potential impact of specific policies on the ecosystem prior to its real application, reducing the risk and considering the population’s needs and scientific findings

Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice

El copyright pertenece a The Rockefeller University PressUnder physiological conditions, the vast majority of T cells differentiate in the thymus, an organ that provides an optimal microenvironment for T cell maturation and shapes the T cell repertoire via positive and negative selection processes. In the present report, we demonstrate that neonatal thymectomy of CBA/H mice results in a diminution of T cells in peripheral lymphoid organs (spleen, lymph nodes), but is followed by a marked transient (12 wk) increase in Thy-1+ CD3+ cells in the peritoneal cavity. These cells exhibit predominantly a double-negative (CD4 - CD8 - ) phenotype among which products of the T cell receptor (TCR) VO11 gene family (i.e., an I-Ereactive TCR normally deleted in I-E-bearing CBA/H mice) are selectively overexpressed . This observation suggests that, under athymic conditions, T cell differentiation and/or accumulation may occur in the peritoneal cavity. Intraperitoneal inoculation of an interleukin 2 (IL2) vaccinia virus construct that releases high titers of human IIr2 in vivo induces conversion of these doublenegative T cells to either CD4+CD8 - or CD4-CD8+ single positives, and allows in vitro stimulation of TCR V,311-bearing cells with a clonotypic antiVO antibody. Since IL-2 induces autoimmune manifestations (DNA autoantibodies, rheumatoid factors, and interstitial nephritis) in thymectomized CBA/H mice, but not in sham-treated littermates, this lymphokine is likely to enhance the autoaggressive function of T cells that bear forbidden, potentially autoreactive TCR gene products and that are normally deleted in the thymus.Peer reviewe

A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy

Background Lung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood. Methods We used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays. Results We show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor. Conclusion These findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.This work was supported by grants to AA: FIS PI15/01491 and CIBER CARDIOVASCULAR from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III with co-funding from the Fondo Europeo de Desarrollo Regional; FEDER