Community Health Workers: Implementing a System in Kentucky

A Community Health Worker (CHW) is a frontline public health worker who is a trusted member of and/or has an unusually close understanding of the community served. This trusting relationship enables the CHW to serve as a liaison/link/intermediary between health/social services and the community to facilitate access to services and improve the quality and cultural competence of service delivery. A CHW also builds individual and community capacity by increasing health knowledge and self-sufficiency through a range of activities such as outreach, community education, informal counseling, social support and advocacy. (American Public Health Association) Recognized as professional members of the health care workforce who effectively address social determinants of health and reduce health disparities (US Department of Health and Human Services) Roles and Responsibilities: Outreach and community mobilization Community/cultural liaison Case management and care coordination Home-based support Health promotion and health coaching System navigation Participatory researc

Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Genome-Wide Association Study for Maize Leaf Cuticular Conductance Identifies Candidate Genes Involved in the Regulation of Cuticle Development.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (g c) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of g c of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with g c were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and β-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of g c in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of g c and have the potential to help breeders more effectively develop drought-tolerant maize for target environments

Best Practices for Educational Interpreters in South Carolina

The purpose of this reference is to provide districts, charter schools, and state operated programs with best practices for working with educational interpreters including, but not limited to, roles and responsibilities, code of professional conduct, and suggested credentialing. It is not required by regulation but is simply the most up-to-date recommendation from the field

Air Quality and Road Emission Results for Fort Stewart, Georgia

The Directorate of Public Works Environmental & Natural Resources Division (Fort Stewart /Hunter Army Airfield) contracted with the Pacific Northwest National Laboratory (PNNL) to monitor particulate matter (PM) concentrations on Fort Stewart, Georgia. The purpose of this investigation was to establish a PM sampling network using monitoring equipment typically used in U.S. Environmental Protection Agency (EPA) ''saturation sampling'', to determine air quality on the installation. In this initial study, the emphasis was on training-generated PM, not receptor PM loading. The majority of PM samples were 24-hr filter-based samples with sampling frequency ranging from every other day, to once every six days synchronized with the EPA 6th day national sampling schedule. Eight measurement sites were established and used to determine spatial variability in PM concentrations and evaluate whether fluctuations in PM appear to result from training activities and forest management practices on the installation. Data collected to date indicate the average installation PM2.5 concentration is lower than that of nearby urban Savannah, Georgia. At three sites near the installation perimeter, analyses to segregate PM concentrations by direction of air flow across the installation boundary indicate that air (below 80 ft) leaving the installation contains less PM2.5 than that entering the installation. This is reinforced by the observation that air near the ground is cleaner on average than the air at the top of the canopy

The effect of different types of hepatic injury on the estrogen and androgen receptor activity of liver

Mammalian liver contains receptors for both estrogens and androgens. Hepatic regeneration after partial hepatectomy in male rats is associated with a loss of certain male-specific hepatic characteristics. In this study we investigated the effects of lesser forms of hepatic injury on the levels of estrogen and androgen receptor activity in the liver. Adult male rats were subjected to portacaval shunt, partial portal vein ligation, hepatic artery ligation, or two-thirds partial hepatectomy. Another group of animals was treated with cyclosporine. At the time of sacrifice the livers were removed and used to determine the estrogen and androgen receptor activity in the hepatic cytosol. A significant reduction (p < 0.05) in the hepatic cytosolic androgen receptor activity and a slight increase in the estrogen receptor activity occurred following total portosystemic shunting. Partial ligation of the portal vein, which produces a lesser degree of portosystemic shunting, had no effect on the levels of the estrogen and androgen receptor activity present within hepatic cytosol. Cyclosporine-treated animals had significantly greater (p < 0.01) levels of estrogen receptor activity in the hepatic cytosol compared to vehicle-treated control animals. Levels of estrogen and androgen receptor activity within the hepatic cytosol remained unchanged after ligation of the hepatic artery. The reduction in the cytosolic estrogen and androgen receptor activity in the liver after partial hepatectomy was confirmed. In summary, certain types of hepatic injury are associated with profound changes in the estrogen and androgen receptor content within the liver. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P<0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P<0.01) and thymidine kinase activity (P<0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P<0.05) in the rats treated with cyclosporine as compared to the vehicle. These results show that cyclosporine treatment causes an increase in the hepatic content of estrogen receptor activity that is associated with an enhanced potential for a regenerative response. These effects of cyclosporine treatment on the sex hormone receptor levels in liver may explain the mechanisms responsible for some of the untoward effects of treatment with this agent. © 1990 Plenum Publishing Corporation

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Different mechanisms for resistance to trastuzumab versus lapatinib in HER2- positive breast cancers -- role of estrogen receptor and HER2 reactivation

Introduction: The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs. Methods: Response to L + T treatment was characterized in a panel of 13 HER2-positive cell lines to identify lines that were de novo resistant. Acquired resistant lines were then established by long-term exposure to increasing drug concentrations. Levels and activity of HER2 and estrogen receptor (ER) pathways were determined by qRT-PCR, immunohistochemistry, and immunoblotting assays. Cell growth, proliferation, and apoptosis in parental cells and resistant derivatives were assessed in response to inhibition of HER or ER pathways, either pharmacologically (L, T, L + T, or fulvestrant) or by using siRNAs. Efficacy of combined endocrine and anti-HER2 therapies was studied in vivo using UACC-812 xenografts. Results: ER or its downstream products increased in four out of the five ER+/HER2+ lines, and was evident in one of the two intrinsically resistant lines. In UACC-812 and BT474 parental and resistant derivatives, HER2 inhibition by T reactivated HER network activity to promote resistance. T-resistant lines remained sensitive to HER2 inhibition by either L or HER2 siRNA. With more complete HER2 blockade, resistance to L-containing regimens required the activation of a redundant survival pathway, ER, which was up-regulated and promoted survival via various Bcl2 family members. These L-and L + T-resistant lines were responsive to fulvestrant and to ER siRNA. However, after prolonged treatment with L, but not L + T, BT474 cells switched from depending on ER as a survival pathway, to relying again on the HER network (increased HER2, HER3, and receptor ligands) to overcome L's effects. The combination of endocrine and L + T HER2-targeted therapies achieved complete tumor regression and prevented development of resistance in UACC-812 xenografts. Conclusions: Combined L + T treatment provides a more complete and stable inhibition of the HER network. With sustained HER2 inhibition, ER functions as a key escape/survival pathway in ER-positive/HER2-positive cells. Complete blockade of the HER network, together with ER inhibition, may provide optimal therapy in selected patients

Hanford Site National Environmental Policy Act (NEPA) Characterization

This document describes the U.S. Department of Energy’s (DOE) Hanford Site environment. It is intended to provide a consistent description of the Hanford Site for the many environmental documents being prepared by DOE contractors concerning the National Environmental Policy Act (NEPA). No statements regarding significance or environmental consequences are provided. This year’s report is the eighteen revision of the original document published in 1988 and is (until replaced by the nineteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. Two chapters are included in this document (Chapters 4 and 6), numbered to correspond to chapters typically presented in environmental impact statements (EISs) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology; air quality; geology; hydrology; ecology; cultural, archaeological, and historical resources; socioeconomics; noise; and occupational health and safety. Sources for extensive tabular data related to these topics are provided in the chapter. When possible, subjects are divided into a general description of the characteristics of the Hanford Site, followed by site-specific information, where available, for the 100, 200, 300 and other areas. This division allows the reader to go directly to those sections of particular interest. When specific information on each of these separate areas is not complete or available, the general Hanford Site description should be used. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to NEPA documents prepared for Hanford Site activities. Information in Chapter 6 can be adapted and supplemented with specific information covering statutory and regulatory requirements for use in an environmental assessment or environmental impact statement. When preparing environmental assessments and EISs, authors should consult Recommendations for the Preparation of Environmental Assessments and Environmental Impact Statements published by the DOE Office of NEPA Oversight (DOE 2004). Additional direction and guidance on the preparation of DOE NEPA documents can be found at http://tis.eh.doe.gov/nepa/guidance.html. Individuals seeking baseline data on the Hanford Site and its past activities may also use the information contained in this document to evaluate projected activities and their impacts. Pacific Northwest National Laboratory (PNNL) staff prepared individual sections of this document, with input from other Hanford Site contractors with the best available information through May 2007. More detailed data are available from reference sources cited or from the authors. For this 2007 revision, the following sections of the document were reviewed by the authors and updated with the best available information through May 2005: Climate and Meteorology Air Quality Geology – Seismicity section only Hydrology – Flow charts for the Columbia and Yakima rivers only Ecology – Threatened and Endangered Species subsection only Socioeconomics Occupational Safety All of Chapter 6