Genetic Landscape of Pediatric Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are acquired heterogeneous hematopoietic clonal disorders primarily seen in the adult and elderly populations that presents a variety of cellular morphologies in cell lineages, varying prognoses, and differences in overall survival (OS) between individual patients. The occurrence of MDS in the pediatric and young adult population, or those between the ages of 0 and 29, is slowly on the rise. Pediatric and elderly cases exhibit diverse cytogenetic findings with differences in OS. The characterization of the genetic landscape of pediatric MDS is limited and most studies detailing genetic changes have been conducted in adult MDS cases. In order to aid in therapeutic stratification for pediatric cases, the key genes involved in hematopoietic transformation must be deciphered. This study utilized comprehensive analysis including cytogenetic karyotyping, FISH, and high-resolution microarray techniques. With the use of multiple techniques, this study confirmed the rarity of MDS in the pediatric population, characterized the frequencies of hallmark cytogenetic abnormalities, and identified key aberrations observed at the genetic level. With the use of microarray, we were able to detect genomic aberrations in 33 genes including novel copy number changes in more than one case in the PRDM16, IRF4, MYH11, ALK, CDKN2B, PAX5, EXT2, and ERCC4 genes. The results from this study prove the importance of comprehensive testing utilizing a variety of techniques in distinguishing the most accurate genetic landscape of pediatric MDS. This information can be used to better equip the medical community in accurately diagnosing and providing prognostic implications for therapy and treatment

Sheep and farm level factors associated with contagious ovine digital dermatitis: A longitudinal repeated cross-sectional study of sheep on six farms

Contagious ovine digital dermatitis (CODD) is a cause of severe lameness in sheep in the UK currently affecting approximately 50% of farms. Six farms were studied in North Wales to investigate (1) the prevalence dynamics of CODD, (2) the association between sheep with CODD and potential risk factors and (3) the impact of CODD on lameness in sheep. The farms were visited at approximately two-month intervals between June 2012 and October 2013 and 6515 sheep were examined. The mean sheep level prevalence of CODD varied between farms (2.5–11.9%). Within farms, prevalence may increase in the late summer/early autumn and after housing. Environmental risk factors included larger flocks, lowland pasture, lush pasture and poached pasture. Co-infection of a foot with footrot was strongly associated with CODD in that foot (OR: 7.7 95% CI: 3.9–15.5

Everyday Spatial Behaviors: A Comparison between Individuals with Down Syndrome and Typically Developing Children

Spatial abilities assist in manipulating, constructing, and navigating the physical world and are employed in a number of everyday activities (Newcombe & Shipley, 2014; Montello, 2001). Research suggests that individuals with Down syndrome (DS) perform either at or below the level of their mental-age matched typically developing (TD) controls on visio-spatial tasks, suggesting that this is an area of weakness in individuals with DS (Yang, Conners, & Merrill, 2014). Much of the research examining spatial abilities in people with DS has focused on their performance on laboratory measures of spatial abilities. Yet spatial abilities measured in a laboratory setting are different from everyday spatial behaviors which consist of what one actually does on a daily basis. In this study, we sought to examine everyday spatial behaviors in individuals with DS compared to mental-age matched TD children as indicated by caregiver self-report. We grouped everyday spatial behaviors into four unique spatial categories (e.g., intrinsic static, extrinsic static, intrinsic dynamic, and extrinsic dynamic) based upon Newcombe and Shipley\u27s (2014) conceptualization. Overall, caregiver reports did not significantly differ in terms of the difficulty their child experienced with tasks within each of these categories. However, caregiver reports indicated that individuals with DS have greater difficulty with sense of direction compared to their TD counterparts. Difficulties related to sense of direction may pose limitations in independent living skills (e.g., navigation) among individuals with DS. Limitations and future directions will be discussed

The Collection and Reception of Sexual Antiquities in the Late Nineteenth and Early Twentieth Century

Sexually themed objects from ancient Greece and Rome have been present in debates about our relationship with the past and with sexuality since they were first brought to modern attention in large numbers in the Enlightenment period. However, modern engagement with this type of material has very often been characterised as problematic. This thesis pushes beyond the story of reactionary censorship of ancient depictions of sex to demonstrate how these images were meaningfully engaged with across intellectual life in late nineteenth- and early twentieth-century Britain and America. It makes a significant and timely contribution to our existing knowledge of a key historical period for the development of the modern understanding of sexuality and cultural representations of it, and the central role that antiquity played in negotiating this fundamental aspect of modernity. Crucially, this work demonstrates how sexual antiquities functioned as symbols of pre-Christian sexual, social and political mores, with which to think through, and to challenge, contemporary cultural constructions around sexuality, religion, gender roles and the development of culture itself. It presents evidence of the widespread and prolific acquisition of sexually themed artefacts throughout private and institutional collecting culture. This deliberate seeking out of ancient images of sex is shown to have been motivated by debates on the universal human connection between sex and religion, as part of wider constructions of notions such as ‘culture’ and ‘primitivism’, with Classical material maintaining a central position in these ideas, despite research into increasingly diverse cultures, past and present. The purposeful engagement with sexual imagery from antiquity is also revealed as having acted as a valuable new source of knowledge about ancient sexual life between men which gave new impetus to the negotiation, defence, celebration and promotion of homoerotic desire in contemporary turn of the twentieth century, Western society

Improved measurement for mothers, newborns and children in the era of the Sustainable Development Goals.

BACKGROUND: An urgent priority in maternal, newborn and child health is to accelerate the scale-up of cost-effective essential interventions, especially during labor, the immediate postnatal period and for the treatment of serious infectious diseases and acute malnutrition.  Tracking intervention coverage is a key activity to support scale-up and in this paper we examine priorities in coverage measurement, distinguishing between essential interventions that can be measured now and those that require methodological development. METHODS: We conceptualized a typology of indicators related to intervention coverage that distinguishes access to care from receipt of an intervention by the population in need.  We then built on documented evidence on coverage measurement to determine the status of indicators for essential interventions and to identify areas for development. RESULTS: Contact indicators from pregnancy to childhood were identified as current indicators for immediate use, but indicators reflecting the quality of care provided during these contacts need development. At each contact point, some essential interventions can be measured now, but the need for development of indicators predominates around interventions at the time of birth and interventions to treat infections. Addressing this need requires improvements in routine facility based data capture, methods for linking provider and community-based data, and improved guidance for effective coverage measurement that reflects the provision of high-quality care. CONCLUSION: Coverage indicators for some essential interventions can be measured accurately through household surveys and be used to track progress in maternal, newborn and child health.  Other essential interventions currently rely on contact indicators as proxies for coverage but urgent attention is needed to identify new measurement approaches that directly and reliably measure their effective coverage

Guide to Community Solar: Utility, Private, and Non-Profit Project Development

This guide is designed as a resource for those who want to develop community solar projects, from community organizers or solar energy advocates to government officials or utility managers

Neutralizing Antibody-Resistant Hepatitis C Virus Cell-to-Cell Transmission

Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal anti- bodies and polyclonal immunoglobulin isolated from infected individuals, providing an effective strategy for escaping host humoral immune responses. Chimeric viruses expressing the structural proteins rep- resenting the seven major HCV genotypes demonstrate neutralizing antibody-resistant cell-to-cell trans- mission. HCV entry is a multistep process involving numerous receptors. In this study we demonstrate that, in contrast to earlier reports, CD81 and the tight-junction components claudin-1 and occludin are all essential for both cell-free and cell-to-cell viral transmission. However, scavenger receptor BI (SR-BI) has a more prominent role in cell-to-cell transmission of the virus, with SR-BI-specific antibodies and small-molecule inhibitors showing preferential inhibition of this infection route. These observations highlight the importance of targeting host cell receptors, in particular SR-BI, to control viral infection and spread in the liver

Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF∆mye, LysM.Cre+/−TFflox/flox) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI