Risk Education in Northern Jordan

In 2013 and 2014, the Center for International Stabilization and Recovery at James Madison University led a project funded by the U.S. Department of State’s Office of Weapons Removal and Abatement (PM/WRA) to provide explosive remnants of war risk education to Syrian refugees living in urban areas of northern Jordan. At the time, it was unclear whether the hundreds of thousands of Syrians fleeing the civil conflict and seeking refuge in neighboring countries would be able to return home in the near future, but there was still significant hope this would happen

Clearance at Cultural Heritage Sites

The most mine- and unexploded ordnance (UXO)-contaminated countries in the world have long histories of conflict, as well as histories rich with extensive archeological and cultural records. It is not uncommon for known historical sites to be littered with mines and UXO, especially in regions with hundreds and even thousands of years of rich cultural heritage, such as Central and Southeast Asia and the Caucuses. This presents an added challenge to project teams tasked with clearing and safeguarding the land while also preserving the integrity of cultural heritage sites

MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses

MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted pro-inflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised

Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability

BACKGROUND: Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In rare tumors, where large-scale clinical trials are daunting, this targeted genomic approach offers a new perspective and hope for improved treatments. Cancers of the ampulla of Vater are rare tumors that comprise only about 0.2% of gastrointestinal cancers. Consequently, they are often treated as either distal common bile duct or pancreatic cancers. METHODS: We analyzed DNA from a resected cancer of the ampulla of Vater and whole blood DNA from a 63 year-old man who underwent a pancreaticoduodenectomy by whole genome sequencing, achieving 37× and 40× coverage, respectively. We determined somatic mutations and structural alterations. RESULTS: We identified relevant aberrations, including deleterious mutations of KRAS and SMAD4 as well as a homozygous focal deletion of the PTEN tumor suppressor gene. These findings suggest that these tumors have a distinct oncogenesis from either common bile duct cancer or pancreatic cancer. Furthermore, this combination of genomic aberrations suggests a therapeutic context for dual mTOR/PI3K inhibition. CONCLUSIONS: Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Abstract Background Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available. Case presentation A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient\u2019s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4 , a negative regulator of TP53. Conclusion Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors

Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing

Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients to understand the range of aberrations that are occurring in each tumor. Because our understanding of PAC tumorigenesis is limited, evaluation of separate cases may reveal aberrations, that are less common but may provide relevant information on the disease, or that may represent viable therapeutic targets for the patient. We used next generation sequencing to assess global somatic events across 3 PAC patients to characterize each patient and to identify potential targets. This study is the first to report whole genome sequencing (WGS) findings in paired tumor/normal samples collected from 3 separate PAC patients. We generated on average 132 billion mappable bases across all patients using WGS, and identified 142 somatic coding events including point mutations, insertion/deletions, and chromosomal copy number variants. We did not identify any significant somatic translocation events. We also performed RNA sequencing on 2 of these patients' tumors for which tumor RNA was available to evaluate expression changes that may be associated with somatic events, and generated over 100 million mapped reads for each patient. We further performed pathway analysis of all sequencing data to identify processes that may be the most heavily impacted from somatic and expression alterations. As expected, the KRAS signaling pathway was the most heavily impacted pathway (P<0.05), along with tumor-stroma interactions and tumor suppressive pathways. While sequencing of more patients is needed, the high resolution genomic and transcriptomic information we have acquired here provides valuable information on the molecular composition of PAC and helps to establish a foundation for improved therapeutic selection

The Soft Power of Anglia: British Cold War Cultural Diplomacy in the USSR

This article contributes to the growing literature on the cultural Cold War through an exploration of the British national projection magazine Anglia, produced by the Foreign Office for distribution in the USSR from 1962 to 1992. As well as drawing attention to the significance of national magazines in general, the article sheds light on Britain's distinctive approach to propaganda and cultural diplomacy during the Cold War. It considers why the magazine was set up and endured for so long, despite considerable reservations about its value. It examines how Britain was projected in a manner that accorded with British understandings about the need for ‘subtle’ propaganda. Finally, it addresses the question of the magazine's impact in the USSR

Bright Opportunities for Atmospheric Characterization of Small Planets: Masses and Radii of K2-3 b, c, and d and GJ3470 b from Radial Velocity Measurements and Spitzer Transits

We report improved masses, radii, and densities for four planets in two bright M-dwarf systems, K2-3 and GJ3470, derived from a combination of new radial velocity and transit observations. Supplementing K2 photometry with follow-up Spitzer transit observations refined the transit ephemerides of K2-3 b, c, and d by over a factor of 10. We analyze ground-based photometry from the Evryscope and Fairborn Observatory to determine the characteristic stellar activity timescales for our Gaussian Process fit, including the stellar rotation period and activity region decay timescale. The stellar rotation signals for both stars are evident in the radial velocity data and is included in our fit using a Gaussian process trained on the photometry. We find the masses of K2-3 b, K2-3 c, and GJ3470 b to be 6.48{}-0.93+0.99, 2.14{}-1.04+1.08, and 12.58{}-1.28+1.31 M ⊕, respectively. K2-3 d was not significantly detected and has a 3σ upper limit of 2.80 M ⊕. These two systems are training cases for future TESS systems; due to the low planet densities (ρ < 3.7 g cm-3) and bright host stars (K < 9 mag), they are among the best candidates for transmission spectroscopy in order to characterize the atmospheric compositions of small planets