Critical Acceleration Levels for Free Standing Bridge Abutments

An analytic procedure for predicting threshold accelerations for movement of gravity wall bridge abutments due to earthquake loading is described. The method draws on previous work related to the sliding mode of failure, and a newly developed theory on seismic reduction of bearing capacity. The main contribution of this paper is to present laboratory observations verifying mode of failure and critical acceleration levels predicted by this procedure for model retaining wall bridge abutments subjected to seismic excitation on a shaking table. Three different test series were performed with different interface conditions between the wall, and the bridge deck, soil foundation, and backfill resulting in a variety of modes of wall deformation

Emotional Stressors Faced by Medical Students Expressed Using Cartoons: A Qualitative Study

Purpose: Empathy, a fundamental pillar of medicine, has been shown to decrease in medical school. Increased stress is linked to decreased empathy, but specific stressors remain unclear. The goal of this study was to qualitatively explore specific stressors among third year medical students. Methods: Third year medical students (n=248) participated in Reflection Rounds with a clinician and a member of pastoral care at Thomas Jefferson University and in their final sessions created a cartoon to express sentiments surrounding medicine. Qualitative analysis of the cartoons was conducted on both the images and text. Common themes were identified from the students’ visualizations and each cartoon was coded into one or more of these themes. Words, punctuation, and visual facial expressions were thematically coded, and their frequency was tabulated. Results: The three most common themes in the cartoons were learning (17%), work-life balance (12%), and insecurity (12%). The seven other themes were working with residents, how students are treated, stress, heart, working with attendings, how patients are treated, and burnout. Multiple punctuation marks were present in 34% of the cartoons, and 32% of the cartoons demonstrated a worried facial expression. Some of the prevalent words in the word cloud analysis were “think, know, student, thanks, and time”. Conclusion: The cartoons demonstrated that medical students have multiple worries, namely: work-life balance, insecurity in their position, and time management. These findings may inform future research on emotional burdens that medical students face, and modifications to these burdens may lead to increased empathy.https://jdc.jefferson.edu/aoa_research_symposium_posters/1011/thumbnail.jp

Adult hematopoietic progenitors are pluripotent in chimeric mice

18 pages, 7 figures.Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-­‐renewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-­‐population of CD34+ cells, that naturally expresses genes characteristic of ESCs and those required to generate iPSCs, but have a limited lifespan and do not form teratomas. In addition, these CD34+ cells spontaneously express, without genetic manipulation, genes characteristic of the three embryonic germ layers: i.e., ectodermal neural, mesodermal cardiac muscle, and endodermal pancreatic and intestinal lineage genes (Pessac, B, et al. 2011. Hematopoietic progenitors express embryonic stem cell and germ layer genes. Comptes Rendus Biologies 334: 300-­‐306). This suggested that these cells may be pluripotent. Here we have transplanted these CD34+ bone marrow stem cells from adult male C56Bl/6J ROSA mice, that carry two markers: the ß-­‐galactosidase gene and the male Y chromosome, into blastocysts of wildtype C57Bl/6J mice. These blastocysts develop normally and give rise to healthy adult chimeric mice. Each female ROSA chimeric mouse had a distinct pattern of male organs expressing ß-­‐galactosidase derived from each of the three embryonic germ layers: ectodermal brain, dorsal root ganglia and skin; mesodermal heart, bone and bone marrow; and endodermal pancreas, intestine, and liver. Thus, adult mammals still carry cells that appear to exhibit a developmental potential comparable to ESCs and iPSCs suggesting that CD34+ cells from adult bone marrow could be used for cell therapy

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy

Ultrasound-guided large-core needle biopsies of breast lesions: analysis of 962 cases to determine the number of samples for reliable tumour classification

The objective of this one-institutional study was to determine the number of large-core needle biopsies (LCNB), under three-dimensional ultrasound (3D-US) validation, that are sufficient to obtain a reliable histological diagnosis of a sonographically detectable breast lesion. Over an 28-month period, 962 sonographically guided LCNB were performed under 3D-US validation to assess 962 breast lesions. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Data of 962 biopsied breast lesions were gathered. Surgical follow-up was available for 659 lesions. Breast malignancies were diagnosed by ultrasound-guided LCNB with a sensitivity of 98.2% by performing three cores per lesion. In few cases, the open surgical specimen revealed the presence of invasive carcinomas in contrast to initial LNCB-based classification as ductal carcinomas in situ (DCIS, 11 lesions), lobular carcinoma in situ (one lesion), and atypical ductal hyperpasia (one lesion). Owing to disagreement between classification based on breast-imaging and histological findings, eight of these tumours were subsequently excised. Of the lesions that were removed at the patients' requests despite benign LCNB diagnosis, two were infiltrating carcinoma and one a DCIS. We demonstrate that three 3D-US-guided percutaneous core specimens are sufficient to achieve tissue for a reliable histological assessment of sonographically detectable breast lesions and allow the detection of malignancies with high sensitivity and low rate of false-negative diagnoses

Putative role of the adenosine A3 receptor in the antiproliferative action of N6-(2-isopentenyl)adenosine

We tested a panel of naturally occurring nucleosides for their affinity towards adenosine receptors. Both N6-(2-isopentenyl)adenosine (IPA) and racemic zeatin riboside were shown to be selective human adenosine A3 receptor (hA3R) ligands with affinities in the high nanomolar range (Ki values of 159 and 649 nM, respectively). These values were comparable to the observed Ki value of adenosine on hA3R, which was 847 nM in the same radioligand binding assay. IPA also bound with micromolar affinity to the rat A3R. In a functional assay in Chinese hamster ovary cells transfected with hA3R, IPA and zeatin riboside inhibited forskolin-induced cAMP formation at micromolar potencies. The effect of IPA could be blocked by the A3R antagonist VUF5574. Both IPA and reference A3R agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide (Cl-IB-MECA) have known antitumor effects. We demonstrated strong and highly similar antiproliferative effects of IPA and Cl-IB-MECA on human and rat tumor cell lines LNCaP and N1S1. Importantly, the antiproliferative effect of low concentrations of IPA on LNCaP cells could be fully blocked by the selective A3R antagonist MRS1523. At higher concentrations, IPA appeared to inhibit cell growth by an A3R-independent mechanism, as was previously reported for other A3R agonists. We used HPLC to investigate the presence of endogenous IPA in rat muscle tissue, but we could not detect the compound. In conclusion, the antiproliferative effects of the naturally occurring nucleoside IPA are at least in part mediated by the A3R