Archaeological Testing at the John Brice II (Jennings-Brice) House, 18AP53, 195 Prince George Street, Annapolis, Maryland

In the fall of 1989, emergency excavation was undertaken in conjunction with restoration work at the John Brice II (Jennings-Brice) House, 18AP53. The exact date of construction for this brick home is problematic, and it was hoped that archaeological investigation could provide conclusive evidence to firmly establish the structure's date of construction. Excavation of one 5 X 5 ft. unit revealed the presence of 10 separate soil layers and four features of note, described in detail below. Unfortunately, no builders trench or similar feature by which we might date the house's construction was recovered. Future plans and possibilities for excavation at the property are outlined with the hopes of performing subsequent work at this rich site. We anticipate a focus on the arrangement and changes in use of the houselot, amassing evidence to support the presence of a vernacular garden on the property during the 18th century, as well as researching refuse disposal patterns, and clues to changing lifeways through the 18th century.

Archaeological Testing at 10 Francis Street, Annapolis, Maryland, 18AP55

In August 1990, archaeological investigations were permitted at 10 Francis Street (18AP55). The house on this property dates to the early eighteenth century and the property has had little disturbance since that time. Excavation here has provided an excellent opportunity to learn more about this period of Annapolis' history. Two units were excavated and are described fully within this report. One unit, placed next to the house foundation, revealed an eighteenth-century brick sidewalk beneath the current mid-nineteenth-century brick sidewalk, but it did not contain any builder's trench for the structure. A second unit, randomly place in the back yard, revealed intact stratigraphy dating back to the early eighteenth century. These findings demonstrate the integrity of this site and its potential for future investigation. Any alterations to this property should proceed only after further controlled excavations have taken place.

Impacts of Mountaintop Removal Coal Mining on the Mud River, West Virginia: Selenium Accumulation, Trophic Transfer, and Toxicity in Fish

Selenium (Se) is a micronutrient necessary for the function of a variety of important enzymes; Se also exhibits a narrow range in concentrations between essentiality and toxicity. Oviparous vertebrates such as birds and fish are especially sensitive to Se toxicity, which causes reproductive impairment and defects in embryo development. Selenium occurs naturally in the Earth's crust, but it can be mobilized by a variety of anthropogenic activities, including agricultural practices, coal burning, and mining.

Mountaintop removal/valley fill (MTR/VF) coal mining is a form of surface mining found throughout central Appalachia in the United States that involves blasting off the tops of mountains to access underlying coal seams. Spoil rock from the mountain is placed into adjacent valleys, forming valley fills, which bury stream headwaters and negatively impact surface water quality. This research focused on the biological impacts of Se leached from MTR/VF coal mining operations located around the Mud River, West Virginia.

In order to assess the status of Se in a lotic (flowing) system such as the Mud River, surface water, insects, and fish samples including creek chub (Semotilus atromaculatus) and green sunfish (Lepomis cyanellus) were collected from a mining impacted site as well as from a reference site not impacted by mining. Analysis of samples from the mined site showed increased conductivity and Se in the surface waters compared to the reference site in addition to increased concentrations of Se in insects and fish. Histological analysis of mined site fish gills showed a lack of normal parasites, suggesting parasite populations may be disrupted due to poor water quality. X-ray absorption near edge spectroscopy techniques were used to determine the speciation of Se in insect and creek chub samples. Insects contained approximately 40-50% inorganic Se (selenate and selenite) and 50-60% organic Se (Se-methionine and Se-cystine) while fish tissues contained lower proportions of inorganic Se than insects, instead having higher proportions of organic Se in the forms of methyl-Se-cysteine, Se-cystine, and Se-methionine.

Otoliths, calcified inner ear structures, were also collected from Mud River creek chubs and green sunfish and analyzed for Se content using laser ablation inductively couple mass spectrometry (LA-ICP-MS). Significant differences were found between the two species of fish, based on the concentrations of otolith Se. Green sunfish otoliths from all sites contained background or low concentrations of otolith Se (< 1 µg/g) that were not significantly different between mined and unmined sites. In contrast creek chub otoliths from the historically mined site contained much higher (≥ 5 µg/g, up to approximately 68 µg/g) concentrations of Se than for the same species in the unmined site or for the green sunfish. Otolith Se concentrations were related to muscle Se concentrations for creek chubs (R2 = 0.54, p = 0.0002 for the last 20% of the otolith Se versus muscle Se) while no relationship was observed for green sunfish.

Additional experiments using biofilms grown in the Mud River showed increased Se in mined site biofilms compared to the reference site. When we fed fathead minnows (Pimephales promelas) on these biofilms in the laboratory they accumulated higher concentrations of Se in liver and ovary tissues compared to fathead minnows fed on reference site biofilms. No differences in Se accumulation were found in muscle from either treatment group. Biofilms were also centrifuged and separated into filamentous green algae and the remaining diatom fraction. The majority of Se was found in the diatom fraction with only about 1/3rd of total biofilm Se concentration present in the filamentous green algae fraction

Finally, zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and L-selenomethionine in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). L-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared to controls. Antioxidant rescue of L-selenomethionime induced deformities was attempted in embryos using N-acetylcysteine (NAC). Pretreatment with NAC significantly reduced deformities in the zebrafish embryos secondarily treated with L-selenomethionine, suggesting that oxidative stress may play a role in Se toxicity. Selenite exposure also induced a 6.6-fold increase in glutathione-S-transferase pi class 2 gene expression, which is involved in xenobiotic transformation. No changes in gene expression were observed for selenate or L-selenomethionine-exposed embryos.

The findings in this dissertation contribute to the understanding of how Se bioaccumulates in a lotic system and is transferred through a simulated foodweb in addition to further exploring oxidative stress as a potential mechanism for Se-induced embryo toxicity. Future studies should continue to pursue the role of oxidative stress and other mechanisms in Se toxicity and the biotransformation of Se in aquatic ecosystems.

Development and usability testing of a Web-based decision aid for families of patients receiving prolonged mechanical ventilation.

BACKGROUND: Web-based decision aids are increasingly important in medical research and clinical care. However, few have been studied in an intensive care unit setting. The objectives of this study were to develop a Web-based decision aid for family members of patients receiving prolonged mechanical ventilation and to evaluate its usability and acceptability. METHODS: Using an iterative process involving 48 critical illness survivors, family surrogate decision makers, and intensivists, we developed a Web-based decision aid addressing goals of care preferences for surrogate decision makers of patients with prolonged mechanical ventilation that could be either administered by study staff or completed independently by family members (Development Phase). After piloting the decision aid among 13 surrogate decision makers and seven intensivists, we assessed the decision aid's usability in the Evaluation Phase among a cohort of 30 surrogate decision makers using the Systems Usability Scale (SUS). Acceptability was assessed using measures of satisfaction and preference for electronic Collaborative Decision Support (eCODES) versus the original printed decision aid. RESULTS: The final decision aid, termed 'electronic Collaborative Decision Support', provides a framework for shared decision making, elicits relevant values and preferences, incorporates clinical data to personalize prognostic estimates generated from the ProVent prediction model, generates a printable document summarizing the user's interaction with the decision aid, and can digitally archive each user session. Usability was excellent (mean SUS, 80 ± 10) overall, but lower among those 56 years and older (73 ± 7) versus those who were younger (84 ± 9); p = 0.03. A total of 93% of users reported a preference for electronic versus printed versions. CONCLUSIONS: The Web-based decision aid for ICU surrogate decision makers can facilitate highly individualized information sharing with excellent usability and acceptability. Decision aids that employ an electronic format such as eCODES represent a strategy that could enhance patient-clinician collaboration and decision making quality in intensive care.

No association between TGFB1 polymorphisms and late radiotherapy toxicity: a meta-analysis.

BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. METHODS: We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue. RESULTS: We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size. CONCLUSIONS: This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study.

Assessment of toxicity and biodistribution of recombinant AAV8 vector-mediated immunomodulatory gene therapy in mice with Pompe disease.

A preclinical safety study was conducted to evaluate the short- and long-term toxicity of a recombinant adeno-associated virus serotype 8 (AAV2/8) vector that has been developed as an immune-modulatory adjunctive therapy to recombinant human acid α-glucosidase (rhGAA, Myozyme) enzyme replacement treatment (ERT) for patients with Pompe disease (AAV2/8-LSPhGAApA). The AAV2/8-LSPhGAApA vector at 1.6 × 10(13) vector particles/kg, after intravenous injection, did not cause significant short- or long-term toxicity. Recruitment of CD4(+) (but not CD8(+)) lymphocytes to the liver was elevated in the vector-dosed male animals at study day (SD) 15, and in group 8 animals at SD 113, in comparison to their respective control animals. Administration of the vector, either prior to or after the one ERT injection, uniformly prevented the hypersensitivity induced by subsequent ERT in males, but not always in female animals. The vector genome was sustained in all tissues through 16-week postdosing, except for in blood with a similar tissue tropism between males and females. Administration of the vector alone, or combined with the ERT, was effective in producing significantly increased GAA activity and consequently decreased glycogen accumulation in multiple tissues, and the urine biomarker, Glc4, was significantly reduced. The efficacy of the vector (or with ERT) was better in males than in females, as demonstrated both by the number of tissues showing significantly effective responses and the extent of response in a given tissue. Given the lack of toxicity for AAV2/8LSPhGAApA, further consideration of clinical translation is warranted in Pompe disease.

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration.

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ(2) test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes.

The development of an advanced ship evacuation simulation software product and associated large scale testing facility for the collection of human shipboard behaviour data

When designing a new passenger ship or modifying an existing design, how do we ensure that the proposed design and crew emergency procedures are safe from an evacuation point of view? In the wake of major maritime disasters such as the Herald of Free Enterprise and the Estonia and in light of the growth in the numbers of high density, high-speed ferries and large capacity cruise ships, issues concerned with the evacuation of passengers and crew at sea are receiving renewed interest. In the maritime industry, ship evacuation models offer the promise to quickly and efficiently bring evacuation considerations into the design phase, while the ship is "on the drawing board". maritimeEXODUS-winner of the BCS, CITIS and RINA awards - is such a model. Features such as the ability to realistically simulate human response to fire, the capability to model human performance in heeled orientations, a virtual reality environment that produces realistic visualisations of the modelled scenarios and with an integrated abandonment model, make maritimeEXODUS a truly unique tool for assessing the evacuation capabilities of all types of vessels under a variety of conditions. This paper describes the maritimeEXODUS model, the SHEBA facility from which data concerning passenger/crew performance in conditions of heel is derived and an example application demonstrating the models use in performing an evacuation analysis for a large passenger ship partially based on the requirements of MSC circular 1033.

Acoustic emission testing of paper

Using Acoustic Emission Testing (AET) to determine the onset of paper damage will be demonstrated on tensile coupons made from mechanical pulp. This technique is part of an EU funded project named the Fifth Frame Program. Its aim is to develop methods for determining specific damage mechanisms through AET. Various such techniques of damage detection will be demonstrated in the coming work.

Report on the Testing and Systematic Evaluation of the airEXODUS Aircraft Evacuation Model

This report covers the testing and evaluation of the airEXODUS evacuation model. airEXODUS has been developed for evacuation certification testing, crew training and aircraft design. The report demonstrates the effectiveness of the model.

Investigation into a modular rule-based testing method for testing business rules in scheduling applications

Rule testing in transport scheduling is a complex and potentially costly business problem. This paper proposes an automated method for the rule-based testing of business rules using the extensible Markup Language for rule representation and transportation. A compiled approach to rule execution is also proposed for performance-critical scheduling systems.