Multifrequency electromagnetic geophysical tools for evaluating the hydrologic conditions and performance of evapotranspiration barriers.

Surface barriers are designed to isolate subsurface contaminants for 1000 years or longer, functionally limiting water infiltration and removing the driving force for contaminant transport to groundwater. Cost-effective monitoring is challenging because of the long design life for surface barriers, spatial limitations and finite lifetime of in situ sensors, and performance metrics related to drainage. Hence, ground-penetrating radar (GPR) and electromagnetic induction (EMI) tools were evaluated for use in performance monitoring of surface barriers. GPR and EMI were used to non-invasively interrogate the Prototype Hanford Barrier (PHB), an evapotranspiration-capillary break barrier established in 1994 at the Hanford Site, in southeastern Washington State. Both geophysical methods were evaluated for providing indirect estimates of subsurface moisture content conditions that were compared to point scale measurements from borehole neutron logs. Surveys were performed during characteristically wet and dry periods to observe a range of hydrologic states of the barrier soil. Although EMI surveys were expected to show seasonal changes associated with changes in the bulk conductivity of the barrier soil layers, the effectiveness of the method was limited by the effects of metallic infrastructure embedded in the barrier. GPR estimates of volumetric water content were typically within 2-3% of the highest water contents from neutron probe measurements for both wet and dry periods, providing reasonable estimates of water content. Given that PHB monitoring data over the past 25 years has demonstrated its success in limiting deep drainage, GPR was found to be a cost-effective method for demonstrating continued barrier performance, with a greater capacity to quantify moisture content distributions over much larger areas relative to point measurements.

Radiology of epiploic appendages: acute appendagitis, post-infarcted appendages, and imaging natural history.

Our aim was to demonstrate the imaging characteristics of epiploic appendages in native, acute inflamed/ischemic and post-infarcted states through retrospective imaging analysis, with clinical and pathologic correlation, and to discuss clinical implications. Cases were gathered mostly retrospectively and reviewed for inclusion based on established diagnostic criteria. Radiology report text search was used to find cases, using terms "epiploic," "appendage," "appendagitis," and "peritoneal body." Data records included patient demographics, relevant clinical data, lesion size, location and apparent imaging composition, and the presence of change or stability in features over multiple studies. Pathologic and clinical data were sought and assessed for correlation. Imaging studies of 198 individuals were included (mean age 50, range 9-95), with a total of 228 lesions: 63 acute and 165 non-acute presentations. All included subjects had CT imaging and some had lesions visible on radiographs, MRI, PET/CT, and sonography. 23 subjects had more than one studied lesion. In addition to classic acute appendagitis, more frequently encountered are post-infarcted appendages either in situ along the colon, adhered to peritoneal or serosal surfaces, or freely mobile in the peritoneum as loose bodies. The majority of the non-acute varieties are recognizable due to peripheral calcification that develops over time following ischemic insult. Multiple cases demonstrated the imaging natural history and confirmed pathologic basis for imaging findings. In summary, acute and post-infarcted epiploic appendages have characteristic imaging appearances and natural history which should provide correct diagnosis in most cases. Incidental post-infarcted epiploica are more commonly encountered than acute presentations.

Evaluation of deep vadose zone contaminant flux into groundwater: Approach and case study.

For sites with a contaminant source located in the vadose zone, the nature and extent of groundwater contaminant plumes are a function of the contaminant flux from the vadose zone to groundwater. Especially for thick vadose zones, transport may be relatively slow making it difficult to directly measure contaminant flux. An integrated assessment approach, supported by site characterization and monitoring data, is presented to explain current vadose zone contaminant distributions and to estimate future contaminant flux to groundwater in support of remediation decisions. The U.S. Department of Energy Hanford Site (WA, USA) SX Tank Farm was used as a case study because of a large existing contaminant inventory in its deep vadose zone, the presence of a limited-extent groundwater plume, and the relatively large amount of available data for the site. A predictive quantitative analysis was applied to refine a baseline conceptual model through the completion of a series of targeted simulations. The analysis revealed that site recharge is the most important flux-controlling process for future contaminant flux. Tank leak characteristics and subsurface heterogeneities appear to have a limited effect on long-term contaminant flux into groundwater. The occurrence of the current technetium-99 groundwater plume was explained by taking into account a considerable historical water-line leak adjacent to one of the tanks. The analysis further indicates that the vast majority of technetium-99 is expected to migrate into the groundwater during the next century. The approach provides a template for use in evaluating contaminant flux to groundwater using existing site data and has elements that are relevant to other disposal sites with a thick vadose zone.

Conducting a Feasibility Study in Women's Health Screening Among Women in a Pacific Northwest American Indian Tribe.

Breast and cervical cancers continue to contribute to high cancer mortality rates in American Indian/Alaska Native women; culturally appropriate interventions are needed to influence screening behaviors and to reduce delays in obtaining care. In a pilot feasibility study designed to influence Pacific Northwest American Indian/Alaska Native women's health screening knowledge and behaviors (breast and cervical), we employed a community-based participatory research approach. Data from interviews with study participants, those involved in implementation of the study and observations were included in the analysis. Study questions focused on training of staff, recruitment of participants, and implementation of the protocol and data management. The complexities of translational, transcultural research and the importance of reporting pilot feasibility studies to the advancement of transcultural research are highlighted in the findings of this research effort.

Normalizing: adolescent experiences living with type 1 diabetes.

PURPOSE: The purpose of this research study was to gain a greater understanding of adolescents' experiences living with diabetes and build a theoretical paradigm to inform interventional design. METHODS: Classical grounded theory was utilized; 15 in-depth interviews of 11 subjects were conducted with Caucasian adolescents' ages 11 to 15 with type 1 diabetes. Interviews were recorded and transcribed verbatim. Data were analyzed using constant comparative analysis. Codes were linked to create the paradigm. RESULTS: A theoretical model was developed about the concept of "normalizing." Normalizing is defined as the ability of the adolescents to integrate diabetes into the background of their daily life by creating routines to make diabetes "part of me." Codes identified in normalizing included: (1) recognizing life is changing, (2) taking action to prevent a crisis, (3) disclosing to engage support, (4) taking on the burden of care, (5) accepting the "new normal," and (6) hoping for a normal future. CONCLUSIONS: Normal developmental tasks of adolescence were closely related and contribute to understanding why adolescents struggle with diabetes. These research findings place a different and positive perspective on diabetes management; the focus shifts to supporting wellness and maintaining a normal life rather than on illness. Findings are expected to be of value to health providers working with adolescents with type 1 diabetes, parents, nursing researchers, and adolescents facing the challenge of diabetes management.

Vanishing bone metastases: a pitfall in contrast-enhanced CT in patients with venous thrombosis.

Enhancement patterns of visceral venous collaterals are well documented in cases of superior vena cava obstruction. Only recently has intraosseous venous collateral enhancement been described. We describe an unusual case of vertebral marrow enhancement in the lower thoracic spine related to venous collateral circulation caused by an incidental hemiazygos thrombus. Misinterpretation of this finding can lead to the erroneous interpretation of sclerotic bone metastases.

Developing an academic and American Indian tribal partnership in education: a model of community health nursing clinical education.

American Indian tribes shoulder a heavy burden in health inequities and recognize the value of partnerships with academic institutions. This article describes a unique education model developed through a partnership between a school of nursing and 2 Pacific Northwest tribes to provide clinical education for students. Over 3 years, students and faculty worked with 2 tribal communities to design research and implement education programs.

Getting into trouble: perspectives on stress and suicide prevention among Pacific Northwest Indian youth.

Suicide rates among Indian youth in the United States are two to three times the national average. Although researchers have identified related risk and protective factors, they have limited understanding of the perspectives of youth at risk. In this descriptive, ethnographic study in a Pacific Northwest tribe, the goal was to gain an understanding of the life experiences of the youth. Focus groups and observations were conducted with 30 Indian youth aged between 14 and 19 years in a Pacific Northwest tribe. Youth were asked to talk about their stressors, sense of family/community support, and hopes for the future. Youth reported major stress and noted that friends and family were both a support and also a source of stress. They hoped for strengthening of cultural values, economic development, and opportunities to give their talents to the tribe. These findings provide further insight about suicide risk among Indian youth and advance the understanding of suicide prevention in a transcultural setting.

Research to practice: developing an integrated anaphylaxis education curriculum for school nurses.

The numbers of school-aged children with life-threatening allergies that cause anaphylaxis continues to increase. Many states, including Washington, have responded to this by developing specific guidelines for school districts to follow in order to provide a safe learning environment for children with medical conditions that put them at risk for anaphylaxis. School nurses require resources to assist them in providing health training for school staff on how to manage potentially life-threatening health conditions for children in their school, however, resources to address this training are limited. A search for and content analysis of currently available literature and resources about anaphylaxis and anaphylaxis training curricula revealed a lack of an integrated curriculum to train school staff. This article presents a discussion of the development of a train-the-trainer anaphylaxis education program providing school nurses with curriculum, lesson plans, teaching-learning activities, and resources for anaphylaxis education of all school staff.

Retention of Native American nurses working in their communities.

PURPOSE: The purpose of this study was to describe the experiences of Native American nurses working in their tribal communities to address retention. DESIGN: An interpretive phenomenological study guided by a Native American research agenda and a Native American nursing practice model. METHODS: In-depth interviews with nine Native American nurses were conducted. Data analysis used interpretive phenomenological procedures including an iterative process with Native American consultants and researchers to develop themes. CONCLUSIONS: Native American nurses experienced a great deal of stress and illness as they attempted to fulfill their mission to help their people. The three themes were: (a) paying the price to fulfill my mission, (b) being and connecting holistically, and (c) transcending the system. Recommendations include strategies for nurse educators, tracking the ethnicity of nurses in each Indian Health Service area, documenting their reasons for leaving, and conducting further research to develop community-based interventions to improve retention.

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.

Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.

Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.

Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.

Challenges in community-based participatory research implementation: experiences in cancer prevention with Pacific Northwest American Indian tribes.

BACKGROUND: Much has been written about community-based participatory research (CBPR) history and principles, but few have addressed challenges in implementation in transcultural situations. The goal of this discussion is to address CBPR implementation issues in cancer prevention research with American Indian tribal communities in the Pacific Northwest. METHOD: Information in this discussion is drawn from qualitative research conducted over a 10-year period in which CBPR was employed in cancer prevention research with Pacific Northwest Indian tribes. CBPR principles provide the framework for the discussion: establishing trusting relationships, assuring participation, sharing power, and communicating. RESULTS: In this work, we found that CBPR is appropriate for use in Pacific Northwest Indian tribal communities and is compatible with cultural values. We also found that there are many challenges. Recommendations are provided on needed institutional and structural changes. CONCLUSIONS: CBPR is an important research approach in addressing cancer prevention health disparities among American Indian tribal communities. Continued effort needs to be directed toward creating systems and structures to support researchers in utilizing this method. Findings are of value to researchers aiming to implement CBPR in Indian communities and to practitioners, policy makers, and administrators who make decisions about CBPR funding and support structures.

Healing fractured families: parents' and elders' perspectives on the impact of colonization and youth suicide prevention in a pacific northwest American Indian tribe.

Suicide rates among American Indian youth in the United States are two to three times the national average. Risk factors for American Indian youth include depression, alcohol use, hopelessness and stress, and family conflict, abuse, poverty, and instability. In this descriptive study, the authors aimed to obtain parents' and elders' perspectives on community needs and to identify strengths on which the community might build to reduce youth suicide risk. Data were collected from focus groups with 40 American Indian parents and from individual interviews with 9 American Indian elders. The major task participants addressed was holding the family together and healing intergenerational pains. Topics parents discussed were holding onto cultural values, holding the family together, getting through school, and getting a job. These findings substantiate previous research and provide useful information for the design of culturally appropriate family or community-based interventions to prevent American Indian youth suicide.

Respecting tribal traditions in research and publications: voices of five Native American nurse scholars.

A dialogue with five Native American scholars provides insight into conducting research and publishing resulting manuscripts on Native American topics, specifically healing beliefs and practices. This information provides a means to develop sensitivity and create understanding about concerns held by Native Americans regarding sharing certain defined cultural information with those outside the culture. The article identifies salient tribal issues related to research, discusses perspectives important to tribal nations and Native individuals surrounding research, and supplies a base on which to formulate further discussions.

Clinical course correlates poorly with muscle pathology in nemaline myopathy.

OBJECTIVE: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy. METHODS: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline myopathy due to alpha-actin (ACTA1) mutations and three with mutations in alpha-tropomyosin(SLOW) (TPM3). For each biopsy rod number per fiber, percentage of fibers with rods, fiber-type distribution of rods, and presence or absence of intranuclear rods were documented. RESULTS: Rods were present in all skeletal muscles and diagnosis was possible at all ages. Most biopsies contained nemaline bodies in more than 50% of fibers, although rods were seen only on electron microscopy in 10 patients. Rod numbers and localization correlated poorly with clinical severity. Frequent findings included internal nuclei and increased fiber size variation, type 1 fiber predominance and atrophy, and altered expression of fiber type specific proteins. Marked sarcomeric disruption, increased glycogen deposition, and intranuclear rods were associated with more severe clinical phenotypes. Serial biopsies showed progressive fiber size variation and increasing numbers of rods with time. Pathologic findings varied widely in families with multiple affected members. CONCLUSIONS: Very numerous nemaline bodies, glycogen accumulation, and marked sarcomeric disruption were common in nemaline myopathy associated with mutations in skeletal alpha-actin. Nemaline myopathy due to mutations in alpha-tropomyosin(SLOW) was characterized by preferential rod formation in, and atrophy of, type 1 fibers. Light microscopic features of nemaline myopathy correlate poorly with disease course. Electron microscopy may correlate better with disease severity and genotype.

Nemaline myopathy: a clinical study of 143 cases.

We report 143 Australian and North American cases of primary nemaline myopathy. As classified by the European Neuromuscular Centre guidelines, 23 patients had severe congenital, 29 intermediate congenital, 66 typical congenital, 19 childhood-onset, and 6 adult-onset nemaline myopathy. Inheritance was autosomal recessive in 29 patients, autosomal dominant in 41, sporadic in 72, and indeterminate in 1. Twenty-two patients had skeletal muscle actin mutations and 4 had mutations in the alpha-tropomyosin(slow) gene. Obstetric complications occurred in 49 cases. Seventy-five patients had significant respiratory disease during the first year of life, and 79 had feeding difficulties. Atypical features in a minority of cases included arthrogryposis, central nervous system involvement, and congenital fractures. Progressive distal weakness developed in a minority of patients. Thirty patients died, the majority during the first 12 months of life. All deaths were due to respiratory insufficiency, which was frequently underrecognized in older patients. Arthrogryposis, neonatal respiratory failure, and failure to achieve early motor milestones were associated with early mortality. Morbidity from respiratory tract infections and feeding difficulties frequently diminished with increasing age. Aggressive early management is warranted in most cases of congenital nemaline myopathy.

Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases.

Protein prenylation is a posttranslational lipid modification in which C(15) and C(20) isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Ras protein is farnesylated coupled with the observation that mutant forms of Ras are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Ras-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with (32)P-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta-subunit of this enzyme. These results clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.