ALBERT

Description: Sustainability, Vol. 10, Pages 2907: A Novel Dynamic Insulation System for Windows Sustainability doi: 10.3390/su10082907 Authors: Michael Gruner Barbara Szybinska Matusiak One of the measures to reduce energy consumption in buildings in Nordic countries is limiting the window area, as windows contribute to significantly higher heat loss than walls during a long hot season. This conflicts with user needs for daylight and views out, especially in buildings situated in dense urban areas. The purpose of the project was to test if dynamic insulation can be used to reduce heat loss through windows during periods when view out is not needed. The paper presents a new dynamic insulation system for windows in a form of an exterior sliding shutter. The development of the system started from an existing poorly insulating sliding door system that has been equipped with vacuum insulation panels and re-designed according to the new purpose. The new system was both numerically simulated using THERM and tested in full-scale in a Hot-box apparatus at the laboratory of SINTEF Building and Infrastructure. The results are promising and encourage further development towards a commercial product.

Description: Diamond Blackfan anemia (DBA) is a rare, inherited bone marrow failure syndrome characterized by anemia, congenital anomalies and a predisposition to cancer. The patients usually present during infancy or early childhood, but can also present in adulthood. In the majority of cases DBA is due to a mutation in a small or large ribosomal protein (RP) subunit leading to RP haploinsufficiency. The only treatments for the anemia of DBA are red cell transfusions (accompanied by iron chelation), oral corticosteroid therapy or stem cell transplantation. Pospisilova et al. (Haematologica 2007; 92(5):e66-67) reported one complete and two partial erythroid responses after the use of the branched chain amino acid L-leucine in 6 select patients. In skeletal muscle, leucine supplementation can upregulate components of the protein synthetic machinery, including ribosomal proteins, promoting protein translation. Mouse and fish models of DBA respond with amelioration of anemia to L-leucine. We therefore proposed to study the effect of L-leucine on transfusion dependence and growth in subjects with DBA. Methods: The primary objectives were to determine the feasibility of administering L-leucine in subjects with DBA who are red cell transfusion-dependent and to determine the efficacy of L-leucine to produce a hematologic and growth response. The secondary objective was to determine the safety profile of L-leucine. Twelve study sites were involved in this multi-center, Phase I/II study with an anticipated accrual of 50 subjects. A dose of 700 mg/M2 orally three times per day for 9 months was used. Inclusion criteria included age 〉 2 years, the diagnosis of DBA and transfusion dependence with adequate kidney and liver function. Response was evaluated at 9 months with Complete Response (CR) defined as no further transfusions required and Hb 〉9; Partial Response (PR): Hb 〈 9 gm/dL with an increase in reticulocyte count and transfusion interval; and No Response (NR): no change in transfusion needs, Hb or reticulocyte count . Growth percentiles were evaluated at baseline and at completion of 9 months of treatment and the growth velocity change was calculated. Results: The study opened July 2014 and closed February 2017; 55 subjects were consented; 12 were screen failures; 43 subjects were evaluable. There were 21 males; the median age was 9 years 1 month (2 years 5 months - 46 years 1 month). There were no untoward side effects experienced by any subject that were attributable to the L-leucine. Two subjects had an erythroid CR and 1 subject had a PR. The CRs occurred at 1 month and 3 months after start of L-leucine. The subject with PR had an elevated reticulocyte count but was not able to maintain a Hb 〉9 gm/dL without a transfusion and thus was not transfusion independent. Of the 30 subjects with growth potential who received L-leucine 10 experienced a positive growth velocity change at 9 months of therapy compared to baseline. At a median age of 7.5 years, the mean pre-leucine height percentile was 27 +/- 17.9 and the post-leucine height percentile was 35 +/- 19.9 (p

Description: Background: Increasing evidence indicates that the minimal residual disease in childhood precursor B lymphoblastic leukemia (B-ALL) can predict the clinical outcome of the patients. With the combination of multicolor flow cytometry and B-cell receptor gene rearrangement or gene translocation analysis, the majority of minimal residual disease can be detected at the 10−5 level. However, these methods may suffer from high cost and complexity and result in false negatives due to antigen shift or lack of genetic markers. Aberrant DNA hypermethylation in CpG islands of tumor suppressor genes is a hallmark of many human malignancies including B-ALL. Since the DNA methyltransferase 1 (DNMT1) is a component of replisome at the DNA replication fork, the methylation in cytosine is precisely duplicated in each cell cycle. Thus the DNA methylation status is maintained and can be detected in the minimal residual leukemic cells if the original clone has DNA methylation markers. Methods: We developed a new method for detection of minimal residual disease in B-ALL patients using a specific DNA methylation marker in the promoter region of the tumor suppressor gene DLC-1 (deleted in liver cancer -1). The quantitative real-time methylation specific PCR (qMSP) was utilized as a primary detection method and it was validated via combined bisulfite restriction analysis (COBRA). The qMSP uses two specifically designed amplification primers which are complementary only for bisulfite-treated methylated DNA sequences and an additional fluorogenic probe specificlly hybridizing methylated target amplicons. Results: By using highly sensitive qMSP assay, we demonstrated that DNA methylation of the DLC-1 gene promoter occurred in 15 out of 20 (75 %) of B-ALL patient bone marrow aspirate specimens and 2 (NALM-6 and MN60) out of 3 B-ALL cell lines. DLC-1 methylation was detected in multiple sequential specimens (up to 6 time points) from 3 childhood B-ALL patients and is comparable with morphologic, flow cytometry and B-cell receptor gene rearrangement (in 5 specimens) assessment. In addition, DLC-1 methylation in different types of specimens collected at the same time point including frozen bone marrow aspirate, unstained bone marrow aspirate slides, fresh peripheral blood, and unstained peripheral blood smear showed complete consistency. Finally, the analytic sensitivity of qMSP was determined by a series of dilution of tumor cell DNA (MN60) in normal human genomic DNA. Ten ng of tumor DNA can be detected in 1 μg of normal DNA. The co-efficient of variation (CV) of the intra- and inter- measurements was about 0.5% and 1.5% by Ct values, respectively. Conclusion: We have developed a novel real-time methylation specific PCR method to detect minimal residual disease in B-ALL patients. The method is sensitive, quantitative, simple and fast, and has the potential to be used for routine clinical minimal residual disease detection in majority of B-ALL patients. The analytic sensitivity and specificity of this method are compatible with flow cytometric and molecular analysis. A study with larger number of B-ALL patient specimens using this novel method is currently underway.

Description: Introduction Children and adults with sickle cell disease (SCD) suffer from overt stroke, the prevalence of which has been reported to be 11% 〈 20 years. More commonly, they suffer from silent cerebral Infarction (SCI) that has a reported prevalence of 37.1% in children at 4 years of age1. Unlike homozygous SS disease (HbSS), the reported prevalence of overt and silent stroke in Hemoglobin SC (HbSC) is low (0% and 5.8%, respectively) in Cooperative Study of Sickle Cell Disease (CSSD)2. However, in a recent study, the prevalence of silent stroke in HbSC was found to be 13.5%3. The goal of our study was to determine the prevalence of stroke and neurovascular complications in children and adults with HbSC in the Central Missouri Cohort (MU-SCD). We also examined the demographic and laboratory factors, SCD related complications, and disease modifiers that correlated with stroke in this cohort. Methods We retrospectively analyzed charts of 131 children and adults with (SCD) who sought care at the University of Missouri between 2000 and 2018, between the ages of 1- 65 years. Clinical, laboratory, Transcranial Doppler (TCD) ultrasound, and Magnetic Resonance Imaging/Angiography (MRI/MRA) data for clinically documented overt stroke, SCI and vasculopathy were analyzed. An expert neuroradiologist analyzed all the MRI/MRAs in a blinded manner. Fisher's exact tests for categorical data and two-sided t-tests for continuous data analysis were used. P value

Description: Introduction Red blood Cell (RBC) transfusion therapy is an important disease modifying treatment in sickle cell disease (SCD). RBC alloimmunization is one of the more serious complications associated with transfusion therapy and limits its wider clinical application. This complication can result in both acute and delayed hemolytic reaction in the recipients. It is unknown at this time if alloimmunization can lead to broader downstream end-organ complications in sickle cell disease. In this retrospective study, we analyzed the complications associated with RBC alloimmunization in the Central Missouri SCD cohort following development of allo- antibodies (Allo-Ab). Methods We performed a retrospective chart review of all SCD individuals treated at the University of Missouri Medical Center from December 2000 to 2017. Only SCD patients that received RBC transfusions at the Center were included in the study. A two-tailed student's t-test was used to analyze all continuous variables. Fischer's exact test was used to analyze all categorical variables. Apvalue of