Improving management of a mid-Atlantic coastal barrier island through assessment of habitat condition

AbstractTo achieve desired environmental outcomes, environmental condition and trends need to be rigorously measured and communicated to resource managers, scientists, and a broader general audience. However, there is often a disconnect between responsive ecosystem monitoring and decision making for strategic long-term management. This project demonstrates how historical monitoring data can be synthesized and used for future planning and decision making, thereby closing the management feedback cycle. This study linked disparate datasets, collected for a variety of purposes and across multiple temporal and spatial scales, in order to assess and quantify current habitat conditions. The results inform integrated resource management decision-making at Assateague Island National Seashore (Maryland and Virginia, USA) by using ecological reference conditions to identify monitoring needs, areas of high vulnerability, and areas with potential for improved management. The approach also provides a framework that can be applied in the future to assess the effectiveness of these management decisions on the condition of island habitats, and is a replicable demonstration of incorporating diverse monitoring datasets into an adaptive management cycle

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Influence of Environmental Gradients on the Abundance and Distribution of Mycobacterium spp. in a Coastal Lagoon Estuary▿

Environmental mycobacteria are of increasing concern in terms of the diseases they cause in both humans and animals. Although they are considered to be ubiquitous in aquatic environments, few studies have examined their ecology, and no ecological studies of coastal marine systems have been conducted. This study uses indirect gradient analysis to illustrate the strong relationships that exists between coastal water quality and the abundance of Mycobacterium spp. within a U.S. mid-Atlantic embayment. Mycobacterium species abundance and water quality conditions (based on 16 physical and chemical variables) were examined simultaneously in monthly samples obtained at 18 Maryland and Virginia coastal bay stations from August 2005 to November 2006 (n = 212). A quantitative molecular assay for Mycobacterium spp. was evaluated and applied, allowing for rapid, direct enumeration. By using indirect gradient analysis (environmental principal-components analysis), a strong linkage between eutrophic conditions, characterized by low dissolved-oxygen levels and elevated nutrient concentrations, and mycobacteria was determined. More specifically, a strong nutrient response was noted, with all nitrogen components and turbidity measurements correlating positively with abundance (r values of >0.30; P values of <0.001), while dissolved oxygen showed a strong negative relationship (r = −0.38; P = 0.01). Logistic regression models developed using salinity, dissolved oxygen, and total nitrogen showed a high degree of concordance (83%). These results suggest that coastal restoration and management strategies designed to reduce eutrophication may also reduce total mycobacteria in coastal waters

Ending 40 years of silence: Rationale for a new staging system for soft tissue sarcoma of the head and neck

The tumor, node, metastases (TNM) anatomic staging system plays a pivotal role in cancer care, research, and cancer control activities. Since the first edition of the American Joint Committee on Cancer TNM staging classification published in 1977, soft tissue sarcomas have been staged in an anatomic site agnostic fashion whereby the primary tumor size (T) was categorized as T1 if 5 cm; this remained unchanged through the 7th edition of the TNM. However, soft tissue sarcomas of the head and neck (STSHN) usually present smaller than sarcomas of other sites, but carry a disproportionate risk of local recurrence. Up to 70% of tumors are less than 5 cm at presentation, and therefore classified together as T1. Given the rarity of STSHN, there is a paucity of data to guide progress in their classification. Moreover, the majority of publications only report tumor size as less than or greater than 5 cm, presumably based on conventions of the TNM system that remained unchanged for 40 years, thereby affecting progress of STSHN classification. This formed the impetus for change in the 8th edition in 2 key ways: 1) several soft tissue sarcoma site based changes occurred including STSHN now having its own system, and 2) primary tumor size cut-offs of 2 cm and 4 cm used in STSHN now reflect sizes that head and neck specialists commonly encounter in their practice. This update was pragmatic in modifying the TNM from a system with a T category not serving STSHN and which was originally based on sarcoma data from non-head and neck anatomic sites. The background to this change is outlined which provides a framework in which data can be reported to generate evidence for future staging modifications. Keywords: Head and neck cancer, Soft tissue sarcoma, Cancer staging, TNM stagin

Methodology assessment and recommendations for the Mars science laboratory launch safety analysis.

The Department of Energy has assigned to Sandia National Laboratories the responsibility of producing a Safety Analysis Report (SAR) for the plutonium-dioxide fueled Multi-Mission Radioisotope Thermoelectric Generator (MMRTG) proposed to be used in the Mars Science Laboratory (MSL) mission. The National Aeronautic and Space Administration (NASA) is anticipating a launch in fall of 2009, and the SAR will play a critical role in the launch approval process. As in past safety evaluations of MMRTG missions, a wide range of potential accident conditions differing widely in probability and seventy must be considered, and the resulting risk to the public will be presented in the form of probability distribution functions of health effects in terms of latent cancer fatalities. The basic descriptions of accident cases will be provided by NASA in the MSL SAR Databook for the mission, and on the basis of these descriptions, Sandia will apply a variety of sophisticated computational simulation tools to evaluate the potential release of plutonium dioxide, its transport to human populations, and the consequent health effects. The first step in carrying out this project is to evaluate the existing computational analysis tools (computer codes) for suitability to the analysis and, when appropriate, to identify areas where modifications or improvements are warranted. The overall calculation of health risks can be divided into three levels of analysis. Level A involves detailed simulations of the interactions of the MMRTG or its components with the broad range of insults (e.g., shrapnel, blast waves, fires) posed by the various accident environments. There are a number of candidate codes for this level; they are typically high resolution computational simulation tools that capture details of each type of interaction and that can predict damage and plutonium dioxide release for a range of choices of controlling parameters. Level B utilizes these detailed results to study many thousands of possible event sequences and to build up a statistical representation of the releases for each accident case. A code to carry out this process will have to be developed or adapted from previous MMRTG missions. Finally, Level C translates the release (or ''source term'') information from Level B into public risk by applying models for atmospheric transport and the health consequences of exposure to the released plutonium dioxide. A number of candidate codes for this level of analysis are available. This report surveys the range of available codes and tools for each of these levels and makes recommendations for which choices are best for the MSL mission. It also identities areas where improvements to the codes are needed. In some cases a second tier of codes may be identified to provide supporting or clarifying insight about particular issues. The main focus of the methodology assessment is to identify a suite of computational tools that can produce a high quality SAR that can be successfully reviewed by external bodies (such as the Interagency Nuclear Safety Review Panel) on the schedule established by NASA and DOE

Discovery of 2‑Pyridylureas as Glucokinase Activators

Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of <b>33</b> as a compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice