Comparison of body mass index and body surface area as outcome predictors in patients with systolic heart failure

Background: We investigated whether the ‘obesity paradox’ in heart failure (HF) is influenced by common confounders, and assessed if body surface area (BSA) may correlate more closely than body mass index (BMI) with prognosis. Methods: We studied 630 systolic HF patients at their initial visit to the HF clinic. Body size was measured by BMI and BSA. The association between body indices and mortality was assessed by Cox proportional-hazard analyses. Results: There were 248 deaths during mean follow-up of 39 months. A progressive inverse association of BMI and BSA tertiles (T1–T3) with mortality risk was observed (for BSA: T3, reference, T2, hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.01–1.95, p = 0.04 and T1, HR = 1.78, 95% CI 1.29–2.45, p < 0.001; for BMI: T3, reference, T2, HR = 1.29, 95% CI 0.92–1.79, p = 0.13 and T1, HR = 1.66, 95% CI 1.21–2.27, p = 0.002). The obesity paradox was attenuated after multivariate adjustment, and did not persist after adjustment for age alone (for BMI: T3, reference, T2, HR = 1.13, 95% CI 0.81–1.58, p = 0.47; T1, HR = 1.30, 95% CI 0.94–1.80, p = 0.12; for BSA: T3, reference, T2, HR = 0.96, 95% CI 0.68–1.35, p = 0.82; T1, HR = 1.15, 95% CI 0.82–1.63, p = 0.42). Conclusions: BSA provides prognostic information similar to BMI in systolic HF. However, the obesity paradox of both BMI and BSA in HF may be confounded by the younger age of the obese patients.

Conservation Science and Ethics in the Analytical Studies of Clay Cuneiform Tablets from Ancient Near Eastern Archives

The Late Bronze Age (ca. 1500-1200 BC) constitutes the heyday of the great empires of the ancient Near East (ANE), such as Egypt, Hatti, Mitanni, Babylonia, and Assyria. Centuries of conflicts followed by peaceful relations, marked the interrelations of these superpowers. Rich literary records in the form of archives of cuneiform texts were established. These archives contain abundant tablets whose origin is unknown. Sometimes the letterhead is missing, in other cases, we may have the name of the sender and still ignore his domicile. Further, the location of many ANE countries and cities has not yet been clearly established. Hence, revealing the origin of documents has the potential of shedding new light on the history of the ANE and beyond. The paper will discuss the use of a rich array of nondestructive testing (NDT) and minimally-destructive testing (MDT) methods for studying the composition, technology and provenance of ANE cuneiform tablets. This approach opens new horizons in the interpretation of the clay documents. We applied such analyses on hundreds of tablets from el Amarna, Ras Shamra/Ugarit, Boğazköy/Hattusha, and sites in Cyprus and Israel/Palestine. The research project made during the last decade, serves as the basis for this study. The results raise a set of ethical and practical issues concerning the study and conservation of such precious artifacts

Prediction of Influenza Complications: Development and Validation of a Machine Learning Prediction Model to Improve and Expand the Identification of Vaccine-Hesitant Patients at Risk of Severe Influenza Complications

Influenza vaccinations are recommended for high-risk individuals, but few population-based strategies exist to identify individual risks. Patient-level data from unvaccinated individuals, stratified into retrospective cases (n = 111,022) and controls (n = 2,207,714), informed a machine learning model designed to create an influenza risk score; the model was called the Geisinger Flu-Complications Flag (GFlu-CxFlag). The flag was created and validated on a cohort of 604,389 unique individuals. Risk scores were generated for influenza cases; the complication rate for individuals without influenza was estimated to adjust for unrelated complications. Shapley values were used to examine the model’s correctness and demonstrate its dependence on different features. Bias was assessed for race and sex. Inverse propensity weighting was used in the derivation stage to correct for biases. The GFlu-CxFlag model was compared to the pre-existing Medial EarlySign Flu Algomarker and existing risk guidelines that describe high-risk patients who would benefit from influenza vaccination. The GFlu-CxFlag outperformed other traditional risk-based models; the area under curve (AUC) was 0.786 [0.783–0.789], compared with 0.694 [0.690–0.698] (p-value < 0.00001). The presence of acute and chronic respiratory diseases, age, and previous emergency department visits contributed most to the GFlu-CxFlag model’s prediction. When higher numerical scores were assigned to more severe complications, the GFlu-CxFlag AUC increased to 0.828 [0.823–0.833], with excellent discrimination in the final model used to perform the risk stratification of the population. The GFlu-CxFlag can better identify high-risk individuals than existing models based on vaccination guidelines, thus creating a population-based risk stratification for individual risk assessment and deployment in vaccine hesitancy reduction programs in our health system

Serum microRNAs are promising novel biomarkers. PLoS One 2008;3:e3148

Background: Circulating nucleic acids (CNAs) offer unique opportunities for early diagnosis of clinical conditions. Here we show that microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, are present in bodily fluids and represent new effective biomarkers. Methods and Results: After developing protocols for extracting and quantifying microRNAs in serum and other body fluids, the serum microRNA profiles of several healthy individuals were determined and found to be similar, validating the robustness of our methods. To address the possibility that the abundance of specific microRNAs might change during physiological or pathological conditions, serum microRNA levels in pregnant and non pregnant women were compared. In sera from pregnant women, microRNAs associated with human placenta were significantly elevated and their levels correlated with pregnancy stage. Conclusions and Significance: Considering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers

MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down syndrome.

Children with Down syndrome (DS) are at increased risk for acute myeloid leukemias (ML-DS) characterized by mixed megakaryocytic and erythroid phenotype and by acquired mutations in the GATA1 gene resulting in a short GATA1s isoform. The chromosome 21 microRNA (miR)-125b cluster has been previously shown to cooperate with GATA1s in transformation of fetal hematopoietic progenitors. In this study, we report that the expression of miR-486-5p is increased in ML-DS compared with non-DS acute megakaryocytic leukemias (AMKLs). miR-486-5p is regulated by GATA1 and GATA1s that bind to the promoter of its host gene ANK1. miR-486-5p is highly expressed in mouse erythroid precursors and knockdown (KD) in ML-DS cells reduced their erythroid phenotype. Ectopic expression and KD of miR-486-5p in primary fetal liver hematopoietic progenitors demonstrated that miR-486-5p cooperates with Gata1s to enhance their self renewal. Consistent with its activation of AKT, overexpression and KD experiments showed its importance for growth and survival of human leukemic cells. Thus, miR-486-5p cooperates with GATA1s in supporting the growth and survival, and the aberrant erythroid phenotype of the megakaryocytic leukemias of DS.Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number U10CA098543 and U10CA180886. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The study was also supported by Children with Cancer UK (SI), Samuel Waxman Cancer Research Foundation NY and USA Israel Binational Science Foundation (to SI, JC), Israel Science Foundation I-CORE program (SI and SM), Israel Science Foundation Legacy program (SI), The Shabtai Donollo Italian-Israeli Fellowship program (EV), Kamin program (SM), The Israel Cancer Research Foundation and the Daniel Turnberg UK/Middle East Travel Fellowship from the Academy of Medical Sciences (L.G.), The National Cancer Institute (CA120772), Elana Fund, Herrick Foundation, Kids Without Cancer, and the Ring Screw Textron Chair for Pediatric Cancer Research (JT, YG and SI). Research in the Gottgens laboratory is supported by Leukaemia and Lymphoma Research, the MRC, BBSRC, CRUK, Leukaemia and Lymphoma Society, NIHR Cambridge Biomedical Research Centre and core infrastructure support by the Wellcome Trust to the Wellcome Trust and MRC Cambridge Stem Cell Institute and CIMR. M.R.T. was supported by a Marie Curie Intra-European Fellowship (237296). STC was supported by the American Society of Hematology Scholar Award and Alex's Lemonade Stand Foundation Springboard Grant . We acknowledge the Children’s Oncology Group AML Biology Committee for providing patient samples. We thank Ravi Bhatia for miR-486 vectors and for sharing unpublished data.This is metadata relating to an article that cannot be made open access due to the publisher copyright policy. This article is an exception to the HEFCE Open Access policy

MicroRNAs are present in bodily fluids.

<p>A) microRNA levels in serum samples taken from 2 healthy individuals were measured. The levels of 18 different microRNAs (blue circles, cycle thresholds (C_T) values) and the 4 synthetic RNA ‘spike-ins’ (in the lower left part of the graph) were found to be similar. B) To demonstrate that our extraction and evaluation methods can be applied to other body fluids, the same set of 20 microRNAs examined in serum were assessed in urine samples from 2 healthy individuals. Some microRNAs were undetectable in the urine samples and therefore are not shown. Notably, urine and serum samples demonstrate different microRNA abundance profiles.</p