A critical-density closed Universe in Brans-Dicke theory

In a Brans-Dicke (BD) cosmological model, the energy density associated with some scalar field decreases as \displaystyle a^{{-2}(\frac{\omega_{o}+ {\frac12}%}{\omega_{o}+1})} with the scale factor $a(t)$ of the Universe, giving a matter with an Equation of state $\displaystyle p=-{1/3}(\frac{2+\omega_{o}}{1+\omega_{o}}) \rho$. In this model, the Universe could be closed but still have a nonrelativistic-matter density corresponding to its critical value, $\Omega_{o}=1$. Different cosmological expressions, such as, luminosity distance, angular diameter, number count and ratio of the redshift tickness-angular size, are determined in terms of the redshift for this model.Comment: To appear in MNRAS, 7 pages, 5 eps figure

The Incremental Cooperative Design of Preventive Healthcare Networks

This document is the Accepted Manuscript version of the following article: Soheil Davari, 'The incremental cooperative design of preventive healthcare networks', Annals of Operations Research, first published online 27 June 2017. Under embargo. Embargo end date: 27 June 2018. The final publication is available at Springer via http://dx.doi.org/10.1007/s10479-017-2569-1.In the Preventive Healthcare Network Design Problem (PHNDP), one seeks to locate facilities in a way that the uptake of services is maximised given certain constraints such as congestion considerations. We introduce the incremental and cooperative version of the problem, IC-PHNDP for short, in which facilities are added incrementally to the network (one at a time), contributing to the service levels. We first develop a general non-linear model of this problem and then present a method to make it linear. As the problem is of a combinatorial nature, an efficient Variable Neighbourhood Search (VNS) algorithm is proposed to solve it. In order to gain insight into the problem, the computational studies were performed with randomly generated instances of different settings. Results clearly show that VNS performs well in solving IC-PHNDP with errors not more than 1.54%.Peer reviewe

Elevated expression of c-kit in small venous malformations of blue rubber bleb nevus syndrome

The blue rubber bleb nevus syndrome (BRBNS, syn. bean syndrome) is a rare disease characterized by multiple cutaneous and gastrointestinal venous malformations associated with severe bleeding. However, the underlying molecular mechanisms are unknown and no targeted therapeutic approach exists to date. Here we report the case of a 19-year-old male patient with severe BRBNS in whom we analyzed the expression of tyrosine kinases frequently involved in tumor development by immunohistochemistry (vascular endothelial growth factor receptor-2, stem cell growth factor receptor (c-kit), platelet-derived growth factor receptor-β, and stem cell tyrosine kinase-1). A prominent expression of c-kit was detectable in smaller blood vessels, which also showed a moderate expression of the proliferation marker MIB1. Surprisingly, other growth factor receptors stained negatively. We therefore conclude that pharmacological inhibition of the c-kit signaling pathway in cavernous hemangiomas by selective kinase inhibitors may offer options in the treatment of BRBNS patients

Adjuvant therapy of osteosarcoma—A Phase II trial

BACKGROUND The objective of this study was to estimate the time to treatment failure and survival rate of the three-drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS). METHODS Sixty-three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m 2 and cisplatin at a dose of 120 mg/m 2 , alternating with doxorubicin at a dose of 50 mg/m 2 and ifosfamide at a dose of 8 g/m 2 . Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis. RESULTS Thirty-one of 63 eligible patients died, for a 5-year overall survival rate of 58% (95% confidence interval [95% CI], 46–71%). The median time to treatment failure was 19 months (95% CI, 12–41 months). A good pathologic response (≥ 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon. CONCLUSIONS The regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials. Cancer 2004;100:818–25. © 2004 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34384/1/20021_ftp.pd

An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic stem and progenitor cells induces a preleukemic state in transplanted immunodeficient NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolve into BCP-ALL with spontaneously acquired Cyclin Dependent Kinase Inhibitor 2 A (CDKN2A) deletions, as commonly observed in primary human BCP-ALL. CRISPR mediated gene silencing of CDKN2A in primary human CD34+ cells transduced with activated IL7RA results in robust development of BCP-ALLs in-vivo. Thus, we demonstrate that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.This work was supported by the Israel Science Foundation (# 1178/12 to S.I.), Children with Cancer (UK) (S.I. and T.E.), Swiss Bridge Foundation (S.I.), WLBH Foundation (S.I.), Waxman Cancer Research Foundation (S.I.), US–Israel Binational Science Foundation, Israeli health ministry ERA-NET program (#CANCER11-FP-127 to S.I.), Hans Neufeld Stiftung, the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope (S.I. grants # 00161), the Nevzlin Genomic Center for Precision Medicine in Schneider Children’s Medical Center of Israel, The European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813091 (S.I.) and the Israel Childhood Cancer Foundation (S.I.). I.G. was partially supported by Israeli ministry of Immigrant Absorption.info:eu-repo/semantics/publishedVersio

A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer

This study investigated the maximum tolerated dose of S-1 based on the frequency of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients with locally advanced pancreatic cancer. S-1 was administered orally at escalating doses from 50 to 80 mg m−2 b.i.d. on the day of irradiation during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m−2 seven patients) were enrolled in this trial. At a dose of 70 mg m−2 S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 haemorrhagic gastritis, whereas no patients at doses other than 70 mg m−2 demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed a partial response. The median progression-free survival time and median survival time for the patients overall were 8.9 and 11.0 months, respectively. The recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m−2 day−1. A multi-institutional phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway