More scanning, but not zooming, is associated with diagnostic accuracy in evaluating digital breast pathology slides.

Diagnoses of medical images can invite strikingly diverse strategies for image navigation and visual search. In computed tomography screening for lung nodules, distinct strategies, termed scanning and drilling, relate to both radiologists clinical experience and accuracy in lesion detection. Here, we examined associations between search patterns and accuracy for pathologists (N = 92) interpreting a diverse set of breast biopsy images. While changes in depth in volumetric images reveal new structures through movement in the z-plane, in digital pathology changes in depth are associated with increased magnification. Thus, drilling in radiology may be more appropriately termed zooming in pathology. We monitored eye-movements and navigation through digital pathology slides to derive metrics of how quickly the pathologists moved through XY (scanning) and Z (zooming) space. Prior research on eye-movements in depth has categorized clinicians as either scanners or drillers. In contrast, we found that there was no reliable association between a clinicians tendency to scan or zoom while examining digital pathology slides. Thus, in the current work we treated scanning and zooming as continuous predictors rather than categorizing as either a scanner or zoomer. In contrast to prior work in volumetric chest images, we found significant associations between accuracy and scanning rate but not zooming rate. These findings suggest fundamental differences in the relative value of information types and review behaviors across two image formats. Our data suggest that pathologists gather critical information by scanning on a given plane of depth, whereas radiologists drill through depth to interrogate critical features

S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

<p>Abstract</p> <p>Background</p> <p>S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT) inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF) levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated.</p> <p>Methods</p> <p>The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model.</p> <p>Results</p> <p>S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA.</p> <p>Conclusion</p> <p>S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.</p

Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction

Pharmacological Therapies Targeting Epigenetic Regulatory Mechanisms for Sickle Cell Disease and B-thalassemia

The b-hemoglobinopathies, including sickle cell disease (SCD) and b-thalassemia, are the most widespread genetic diseases worldwide including Pakistan1,2 and impose great demands on the healthcare system. b-thalassemia is caused by an inherited deficit in the production of b-globin chains, while SCD is produced by a mutation of the b-globin gene that triggers polymerization of deoxygenated sickle hemoglobin (HbS). Millions of SCD patients worldwide suffer from chronic hemolytic anemia, painful crises, multisystem organ damage, and reduced life expectancy

Display life and internal cooked color of ground beef from vitamin e-supplemented cattle

Retail display life of ground beef and internal color of patties cooked to four endpoint temperatures (131, 149, 160, and 17 1EF) were determined for ground beef (9% fat) from vitamin E-supplemented (500 and 2000 IU per day) steers. Visual scores indicated that the display time required for the 500 and 2000 vitamin E samples to reach an objectionable reddish-brown/brown color was increased by 12 and 32 hours, respectively, as compared with the 0 vitamin E samples. Patties did not differ in internal cooked color regardless of vitamin E level. Vitamin E was effective in increasing retail display color stability and did not affect cooked color

DISCRIMINATION OF LIPOSOME-DELIVERED RNA BY MAMMALIAN CELLS.

DISCRIMINATION OF LIPOSOME-DELIVERED RNA BY MAMMALIAN CELLS

Engineering Economy Analysis

xx+599hlm;27,5c