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Supplementary Figure 1 from Short-term Prophylactic Tamoxifen Reduces the Incidence of Antiestrogen-Resistant/Estrogen Receptor–Positive/Progesterone Receptor–Negative Mammary Tumors

Preeclampsia is a pregnancy-specific complication with long-term negative outcomes for offspring including increased susceptibility to type 2 diabetes (T2D) in adulthood. In rat Reduced Uteroplacental Perfusion Pressure (RUPP) model of chronic placental ischemia, maternal hypertension in conjunction with intrauterine growth restriction mimics aspects of preeclampsia and resulted in female embryonic day (e)19 offspring with reduced β-cell area and increased β-cell apoptosis compared to offspring of Sham pregnancies. Decreased pancreatic β-cell area persists to Postnatal Day (PD)13 in females and could influence whether T2D develops in adulthood. Macrophage changes also occur in islets in T2D. Therefore, we hypothesized that macrophages are crucial to reduction in pancreatic β-cell area in female offspring following chronic placental ischemia. The macrophage marker CD68 mRNA expression was significantly elevated in e19 and PD13 islets isolated from female RUPP offspring compared to Sham. Postnatal injections of clodronate liposomes into female RUPP and Sham offspring on PD2 and PD9 significantly depleted macrophages compared to animals injected with control liposomes. Depletion of macrophages rescued reduced β-cell area and increased β-cell proliferation and size in RUPP offspring. Our studies suggest that the presence of macrophages is important for reduced β-cell area in female RUPP offspring and changes in macrophages could contribute to development of T2D in adulthood.

Preeclampsia is a pregnancy-specific complication with long-term negative outcomes for offspring, including increased susceptibility to type 2 diabetes (T2D) in adulthood. In a rat reduced uteroplacental perfusion pressure (RUPP) model of chronic placental ischemia, maternal hypertension in conjunction with intrauterine growth restriction mimicked aspects of preeclampsia and resulted in female embryonic day 19 (e19) offspring with reduced β-cell area and increased β-cell apoptosis compared with offspring of sham pregnancies. Decreased pancreatic β-cell area persisted to postnatal day 13 (PD13) in females and could influence whether T2D developed in adulthood. Macrophage changes also occurred in islets in T2D. Therefore, we hypothesized that macrophages are crucial to reduction in pancreatic β-cell area in female offspring after chronic placental ischemia. Macrophage marker CD68 mRNA expression was significantly elevated in e19 and PD13 islets isolated from female RUPP offspring compared with sham. Postnatal injections of clodronate liposomes into female RUPP and sham offspring on PD2 and PD9 significantly depleted macrophages compared with injections of control liposomes. Depletion of macrophages rescued reduced β-cell area and increased β-cell proliferation and size in RUPP offspring. Our studies suggest that the presence of macrophages is important for reduced β-cell area in female RUPP offspring and changes in macrophages could contribute to development of T2D in adulthood.

Despite calls from many composition and rhetoric scholars for instructors of writing to stop teaching prescriptive grammar, a vast number of handbooks intended for college writing classes encourage this tradition. For example, Hacker’s Pocket Style Manual has a section on grammar with instructions for students on how to write appropriately. While Hacker may not intend for her instructions to be taken as dictums, they often are, and much time is spent in many classrooms teaching students these rules of grammar. This article uses the Corpus of Contemporary American English (COCA) to support the calls from composition and rhetoric scholars that prescriptive instruction in grammar is more a hindrance to writing instruction than a benefit. Focusing on a few specifics from frequently used grammar handbooks and illustrating how big data shows the “rules” are incorrect at best, this article argues that, just as scholars of English have begun using big data to better understand literary history, scholars of rhetoric and composition might better understand how to help students to write by understanding patterns within big data. Certainly, this argument recognizes that “common usage” may not necessarily be the most eloquent usage. In making this argument, this article focuses on the [neither or either of X] + Verb construction, where the Verb may have either a plural or a singular form. Our findings illustrate that the “real world” writing is different from what textbooks dictate, and we suggest the data-driven observations need to be appropriately incorporated in writing classes. (University of Minnesota Duluth)

We determined the influence of habitat, landscape, geographic, and climate variables on Sedge Wren (Cistothorus platensis) and Marsh Wren (C. palustris) occurrence in 840 coastal wetland survey points throughout the Great Lakes. Variables included surrounding land use and configuration out to 2000 m; latitude; longitude; temperature; precipitation; and vegetation characteristics within 100 m. Classification trees predicted Sedge Wren occurrence at points in the western Great Lakes with

This investigation examines the spatial and temporal variability of marble gravestone decay throughout West Midlands County and adjacent portions of Warwickshire, Staffordshire, and Worcestershire. Gravestone decay has been used effectively as a quantitative measure of acid deposition. Numerous techniques have been used to assess gravestone decay and each is subject to different sources of error. To minimize error we focus only on marble gravestones that use the flush lead lettering technique. Decay of the marble leaves the lead lettering raised above the surface, and the distance can be measured with the use of a digital micrometer. Gravestone decay can be used to quantify the spatial and temporal distribution of acid deposition. Our gravestone decay database consists of 1417 individual measurements on 591 tombstones in 33 cemeteries and covers the period from 1860 to 2010. Sites range from industrial and residential areas to rural settings. These data allow us to establish the natural background rates of decay, the effects of urban/residential expansion, and the efficacy of environmental regulations. Decay rates vary from a minimum of 0.2 mm/century in remote rural areas to nearly 3.0 mm/century in the Birmingham City Center. The data are corrected for environmental variables, converted to acid deposition rates, and plotted at 10-year intervals from 1890 to 2010.

This study assesses the effects of race, age, sex, and time spent in foster care on rates of psychotropic medication use for children in foster care in 2012.Using existing electronic records through county Social Service and Minnesota Medical Assistance databases, 626 children were identified using the inclusion criteria of having been in foster care for at least 30 days during 2012 in St. Louis County, Minnesota. All prescriptions for dispensed psychotropic medications were identified into the following classes: antidepressants, attention-deficit/hyperactivity disorder (ADHD) medications, antipsychotics, alpha-agonists, and other (including anticonvulsants/mood stabilizers, lithium, benzodiazepines, and sedative hypnotics).Overall, 26% of children were dispensed at least one psychotropic medication during the year with the percentage of children on medication for each race as follows: American Indian (AI) 23.3%, European American (EA) 29.2%, and African American (AA) 18.3%. AI children were significantly less likely to be dispensed any psychotropic medication and ADHD medication. EA children, males, and older children received psychotropic medications from significantly more classes than AI or AA children, females, and younger children. Males were significantly more likely to be dispensed alpha-agonists, antipsychotics, and ADHD medications. Increased time since placement into foster care was also significantly associated with increased dispensing rates of antidepressants, ADHD medication, and multiple medication classes.The results of this study show that non-EA children, in particular AI children, were dispensed psychotropics both overall and across different medication classes less often compared to other racial groups. While the reasons for this difference are not known, future studies are needed to address whether mental health needs of all children in foster care are being appropriately addressed, accounting for need and patient preference.

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach.

Overbank flooding is thought to be a critical process controlling nitrogen retention and cycling. Yet, studies aimed at quantifying these effects, specifically nitrification, are relatively few. In this study, we investigated the effects of season and flood frequency on soil nitrification rates in forested floodplains of Upper Mississippi River, Pool 8. Samples were collected from three plots within each site in April, August and November 2006. Plots were equally divided among three flood frequency categories as follows: rare, moderate and frequent based on elevation and flood probability model. We found a significant difference in nitrification rates among flood frequency categories as follows: rare moderate>frequent (F=4.49,p summer>autumn (F=8.88,p

Background Worksite obesity prevention interventions using an ecological approach may hold promise for reducing typical weight gain. The purpose of this study was to examine the effectiveness of Go!, an innovative 12-month multi-component worksite obesity prevention intervention. Methods A quasi-experimental non-equivalent control group design was utilized; 407 eligible hospital employees (intervention arm) and 93 eligible clinic employees (comparison arm) participated. The intervention involved pedometer distribution, labeling of all foods in the worksite cafeteria and vending machines (with calories, step equivalent, and a traffic light based on energy density signaling recommended portion), persuasive messaging throughout the hospital, and the integration of influential employees to reinforce healthy social norms. Changes in weight, BMI, waist circumference, physical activity, and dietary behavior after 6 months and 1 year were primary outcomes. Secondary outcomes included knowledge, perceptions of employer commitment to employee health, availability of information about diet, exercise, and weight loss, perceptions of coworker support and frequency of health discussions with coworkers. A process evaluation was conducted as part of the study. Results Repeated measures ANCOVA indicated that neither group showed significant increases in weight, BMI, or waist circumference over 12 months. The intervention group showed a modest increase in physical activity in the form of walking, but decreases in fruit and vegetable servings and fiber intake. They also reported significant increases in knowledge, information, perceptions of employer commitment, and health discussions with peers. Employees expressed positive attitudes towards all components of the Go! intervention. Conclusions This low-intensity intervention was well-received by employees but had little effect on their weight over the course of 12 months. Such results are consistent with other worksite obesity prevention studies using ecological approaches. Implementing low-impact physical activity (e.g., walking, stair use) may be more readily incorporated into the worksite setting than more challenging behaviors of altering dietary habits and increasing more vigorous forms of physical activity. Trial Registration This study was registered with clinicaltrials.gov (NCT01585480) on April 24, 2012. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-2828-0) contains supplementary material, which is available to authorized users.

Each autumn, tens of thousands of raptors pass over Hawk Ridge in Duluth, Minnesota, on their southbound migration, but migratory pathways leading to Hawk Ridge are unknown. To address this issue, we counted migrating raptors between mid-August and mid-November 2008 from 24 observation points along eight transects perpendicular to the shoreline between Duluth and the Minnesota-Canadian border. Our goals were to determine migratory pathways over a large area (>2000 km2) and identify how these movements were affected by weather, time of day, season, and characteristics of the landscape. A total of 4303 raptors of 14 different species were counted during the 2008 migration season. Exploratory analyses suggested that migratory raptors concentrated near the northern shoreline of Lake Superior, particularly during midday when winds are westerly. Average migration height differed between soaring raptors (buteos and eagles) and accipiters, with >40% of soaring raptors observed higher than 100 m above the...

Large sand bed loads in trout stream headwaters can limit salmonid spawning habitat and reproductive success. This phenomenon has been observed in many northern Wisconsin watersheds, where historic logging practices are the likely source of the sediment loading. Presently, sediment transport is limited by abundant woody debris, causing channels to aggrade and bury gravels. We evaluated the impacts of a wood debris and beaver dam removal remediation strategy on fine sediment transport and exposure of the underlying gravel and cobble substrates in a second-order Lake Superior tributary. A 300-m treatment reach received selective wood removals and was compared with both an upstream 300-m reference reach receiving no alteration and a downstream reach to monitor the effects of transferred fine sediment. Physical channel measurements were taken before the wood removal process, with repeat sampling at 10 and 12 months posttreatment. The wood removal treatment resulted in a significant 25% narrowing of m...

Objective To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a randomized, double-blind, placebo-controlled trial. Methods Adult primary care patients in Duluth, Minnesota, were screened for vitamin D deficiency in February 2007. Participants completed questionnaires pertaining to a variety of symptoms, vitamin D intake, and selected medical conditions. Patients with mild to moderate vitamin D deficiency (25-hydroxyvitamin D [25(OH)D], 10-25 ng/mL) participated in a randomized controlled trial (RCT) of vitamin D replacement and its effect on symptoms. Participants were randomly assigned to receive 50000 units of cholecalciferol (vitamin D3) weekly or placebo for 8 weeks. Patients with severe vitamin D deficiency (25[OH]D Results A total of 610 patients underwent initial screening, and 100 patients with mild to moderate vitamin D deficiency participated in the RCT. Thirty-eight severely deficient patients were treated in an unblinded fashion. On initial screening, 46.2% of participants were deficient in vitamin D. Self-reported vitamin D supplementation, milk intake, celiac disease, gastric bypass, and chronic pancreatitis were predictive of vitamin D status. Severely deficient participants reported increased musculoskeletal symptoms, depression (including seasonal), and higher (worse) scores on a fibromyalgia assessment questionnaire. In the RCT, the treated group showed significant improvement in fibromyalgia assessment scores (P = 0.03), whereas the placebo-treated participants did not. Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later. Conclusions Compared with participants in the placebo group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living. (Endocr Pract. 2009;15:203-212)

Upland breeding bird communities were sampled from 225 points in 15 survey routes in the coastal region of western Lake Superior to examine relationships to human land use. Eighty-four species were detected and 50 were abundant enough to be included in data analysis. Monotonic quadratic regression models were constructed for these 50 species by using species counts as the dependent variable and the proportion of human conversion of the landscape (residential, agriculture, and commercial/industrial land uses) within each study area as the independent variable. Twenty-seven bird species had significant regressions (P < 0.05), 18 of which generally avoided areas developed by humans and 9 of which were attracted to development. Detrended correspondence analysis using counts of these 27 bird species was used to investigate multivariate, community responses to development. The first DCA axis was interpreted as a gradient from urban avoiding to urban exploiting bird species and was strongly correlated with land cover variables related to human development. Our results advance the idea that breeding bird communities can be used as indicators of ecological condition and can diagnose potential causes for changes in these conditions. Further, our study points out the usefulness of bird monitoring data in regional planning efforts that incorporate goals for maintaining native biological diversity.

One goal in indicator development is to implement long-term monitoring that will track the relative condition of the indicator over time. Among the first steps in establishing a monitoring program is to develop a sampling design that adequately characterizes the indicator to be monitored as well as the cost-effectiveness of the program. We used breeding bird data collected in Lake Superior and Lake Michigan coastal wetlands (riverine, lacustrine, barrier-protected) to determine: 1) how to select individual wetlands for sampling, 2) optimum number of sample points per wetland, 3) optimal daily sampling period, 4) how many times to sample, and 5) the costs associated with implementing a monitoring program for breeding bird communities of wetlands across the Great Lakes. We found that wetlands selected for sampling should represent the range of wetlands sizes available for monitoring and that the most cost-effective strategy would be to sample a maximum of three points, even in the largest wetlands....

Developing indicators of ecosystem condition is a priority in the Great Lakes, but little is known about appropriate spatial scales to characterize disturbance or response for most indicators. We surveyed birds, fish, amphibians, aquatic macroinvertebrates, wetland vegetation, and diatoms at 276 coastal wetland locations throughout the U.S. Great Lakes coastal region during 2002-2004. We assessed the responsiveness of 66 candidate indicators to human disturbance (agriculture, urban devel- opment, and point source contaminants) characterized at multiple spatial scales (100, 500, 1,000, and 5,000 m buffers and whole watersheds) using classification and regression tree analysis (CART). Non- stressor covariables (lake, ecosection, watershed, and wetland area) accounted for a greater proportion of variance than disturbance variables. Row-crop agriculture and urban development, especially at

Frogs and toads (anurans) are sensitive to a variety of anthropogenic stressors and are widely suggested as indicators of ecological condition. We surveyed 220 coastal wetlands along the U.S. shores of the Laurentian Great Lakes and quantified relationships between presence of anuran species and degree of anthropogenic disturbance. Results were used to derive explicit, functional relationships between environmental condition and anuran occurrences. These functions were subsequently used to calculate a multi-species indicator of ecological condition at other (novel) wetlands. Of 14 anuran species observed, spring peeper (Pseudacris crucifer) exhibited the strongest and most consistent relationship with environmental condition across the entire study area. Other species exhibited significant relationships with the environmental gradient, but the direction of association varied geographically or the overall species abundance was very low (e.g., mink frog, Rana septentrionalis). Even if applied to separate ecological provinces (Laurentian Mixed Forest or Eastern Deciduous Forest), multi-species estimates of wetland condition based on anurans are not much better indicators of environmental condition based on human disturbance than are indices based solely on occurrence of spring peeper. Nevertheless, indicators grounded in explicit relationships with environmental stress are superior to traditional measures (e.g., species richness) that combine species with different responses to the stress gradient. At least one anuran species (spring peeper) can contribute meaningfully to the assessment of ecological condition in Great Lakes coastal wetlands; its value as an indicator will be improved if it can be combined with information from other wetland species such as birds, fishes, and vascular plants.

We use bird distributions in non-forested coastal wetlands of the Great Lakes to illustrate a new, conceptually explicit method for developing biotic indicators. The procedure applies a probabilistic framework to derive an index that best “fits” an observed assemblage of species, based on preliminary information about species’ responses to human environmental disturbance. Among 215 coastal wetland complexes across the U.S. portion of the Great Lakes, 23 bird species were particularly sensitive (positively or negatively) to a multivariate environmental disturbance gradient ranging from 0 (maximally disturbed) to 10 (minimally disturbed). Species like Sandhill Crane (Grus canadensis) and Sedge Wren (Cistothorus platensis) showed strong negative relationships with human disturbance, while others like Common Grackle (Quiscalus quiscula), American Robin (Turdus migratorius), and European Starling (Sturnus vulgaris), showed strong positive relationships with disturbance. The functional shapes of these biotic responses were used to determine indices of ecological condition (IEC) for new sites. Values of IEC were highly correlated with the environmental gradient, but deviations from a 1:1 relationship reveal novel insights about local ecological conditions. For example, sites dominated by invasive plant species like Phragmites australis tended to yield IEC values that were lower than expected based on the environmental gradient. This framework for calculating ecological indicators holds significant potential for other applications because it is flexible, explicitly linked to a disturbance gradient, and easy to calculate once standardized biotic response functions are documented and made available for a region of interest.

We introduce a new method for quantifying the ecological condition (C) of sites based on documented species’ responses to environmental stress. Preliminary research is needed to establish species-specific logistic functions, representing probabilities of finding individual species across an explicit reference gradient, ranging from maximally stressed (C = 0) to minimally stressed (C = 10) localities. Each function takes into account the species’ tolerance to stress, the species’ overall ubiquity, and the probability of detecting the species when it is present. Given a set of standardized species-specific functions, the ecological condition of any site can be derived by iteration, converging on the value of C that best ‘‘predicts’’ the species that are actually present. Species from multiple taxonomic groups can be included in the calculations, and results are not directly affected by species richness or sampling area. We demonstrate a successful application of this method for bird species assemblages in the U.S. portion of the Great Lakes coastal zone. Approximately, 28% of the bird species observed in the Eastern Deciduous Forest Ecological Province and 35% of the species in the Laurentian Mixed Forest Ecological Province showed strong relationships with a reference gradient of land cover variables. Functional stress–response relationships of these species can be used effectively to estimate ecological condition at new sites. The estimated condition based on bird species generally mirrors the reference condition, but deviations from the expected 1:1 relationship provide meaningful insights about ecological condition of the target areas. Sensitivity analysis using different numbers of species shows that our method is robust and can be applied consistently with 25–30 species exhibiting strong stress–response functions. # 2006 Elsevier Ltd. All rights reserved.

Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data usingAspergillus as allergen to identify putative asthma 'signature genes', i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.

We examined how geographic distribution of birds and their affinities to three geomorphic wetland types would affect the scale at which we developed indicators based on breeding bird communities for Great Lakes coastal wetlands. We completed 385 breeding bird surveys on 222 wetlands in the US portion of the basin in 2002 and 2003. Analyses showed that wetlands within two ecoprovinces (Laurentian Mixed Forest and Eastern Broadleaf Forest) had different bird communities. Bird communities were also significantly different among five lakes (Superior, Michigan, Huron, Erie, and Ontario) and among three wetland types (lacustrine, riverine, barrier-protected). Indicator values illustrated bird species with high affinities for each group (ecoprovince, lake, wetland type). Species with restricted geographic ranges, such as Alder and Willow Flycatchers (Empidonax alnorum and E. traillii), had significant affinities for ecoprovince. Ten bird species had significant affinities for lacustrine wetlands. Analyses on avian guild metrics showed that Lake Ontario wetlands had fewer long-distant migrants and warblers than other lakes. Numbers of short-distant migrants and total individuals in wetlands were higher in the Eastern Broadleaf Forest ecoprovince. Number of flycatchers and wetland obligate birds were not different among provinces, lakes, or wetland type. One potential indicator for wetland condition in Great Lakes wetlands, proportion of obligate wetland birds, responded negatively to proportion of developed land within 1 km of the wetland. We conclude that, although a guild approach to indicator development ameliorates species-specific geographic differences in distribution, individual species responses to disturbance scale will need to be considered in future indicator development with this approach.

The Floristic Quality Index (FQI) has been proposed as a tool that can be used to identify areas of high conservation value, monitor sites over time, assess the anthropogenic impacts affecting an area, and measure the ecological condition of an area. FQI is based on the Coefficient of Conservatism (C), which is a numerical score assigned to each plant species in a local flora, primarily from best professional judgment, that reflects the likelihood that a species is found in natural habitats. FQI is computed by multiplying the mean Coefficient of Conservatism (C) by the square root of species richness for an observational unit. Great Lakes coastal wetlands were used to assess the properties and performance of various species richness, Coefficient of Conservatism, and Floristic Quality indices, as well as compare C-value assignments from two U.S. states (Wisconsin and Michigan). FQI and species richness increased with sampling area according to a power function, but C more or less remained constant. Sampling schemes should therefore focus on controlling sampling area and minimally sampling each community type at a site. In some cases, Wisconsin and Michigan assigned different values of C to the same species, highlighting possible effects due to the somewhat subjective nature of C-value assignment. Coefficient of Conservatism and Floristic Quality indices were better at discriminating differences between sites, independent of a condition gradient, than species richness alone, but neither index type outperformed the other. Both types of indices were also found to be acceptable ecological indicators of condition, although Floristic Quality indices consistently outperformed Coefficient of Conservatism indices in this capacity. Regardless of the subjectivity involved with the assignment of C-values and that ‘floristic quality’ is a human concept and not a true ecosystem property, both Coefficient of Conservatism and Floristic Quality indices seem to be effective indicators of condition in Great Lakes coastal wetland

Understanding the relationship between human disturbance and ecological response is essential to the process of indicator development. For large-scale observational studies, sites should be selected across gradients of anthropogenic stress, but such gradients are often unknown for a population of sites prior to site selection. Stress data available from public sources can be used in a geographic information system (GIS) to partially characterize environmental conditions for large geographic areas without visiting the sites. We divided the U.S. Great Lakes coastal region into 762 units consisting of a shoreline reach and drainage-shed and then summarized over 200 environmental variables in seven categories for the units using a GIS. Redundancy within the categories of environmental variables was reduced using principal components analysis. Environmental strata were generated from cluster analysis using principal component scores as input. To protect against site selection bias, sites were selected in random order from clusters. The site selection process allowed us to exclude sites that were inaccessible and was shown to successfully distribute sites across the range of environmental variation in our GIS data. This design has broad applicability when the goal is to develop ecological indicators using observational data from large-scale surveys.

Dietary samples from nestling Tree Swallows (Tachycineta bicolor) in northwestern Minnesota were compared to invertebrate availability as measured by aerial tow nets. The majority of the biomass in the nestlings' diet was adult insects with larval stages of aquatic origin, while absolute numbers of insects of both aquatic and terrestrial origin were similar. Orders of invertebrates in the diet and available were similar in number but not in biomass. Diet showed little variation by time of day, date of sampling or the age of the nestling. The mean number of odonates in the nestling Tree Swallows' diet increased exponentially as the percentage of open water and open water + cattail marsh increased within a 400-m foraging radius.Dieta de los Pichones de Tachycineta bicolorResumen. Se compararon muestras dietarias de pichones de la golondrina Tachycineta bicolor tomadas en el noroeste de Minnesota con la disponibilidad de invertebrados medida con redes aéreas. La mayor parte de la biomasa en la dieta de los pichones correspondió a insectos adultos con estadíos larvales de origen acuá tico, mientras que los números absolutos de insectos de origen acuático y no acuático fueron similares. Los órdenes de invertebrados presentes en la dieta y disponibles en el ambiente fueron similares en números pero no en biomasa. La dieta mostró poca variación entre horas del día, fechas de muestreo o edad de los pichones. El número promedio de odonatos en la dieta de los pichones de T. bicolor aumentó exponencialmente a medida que se incrementó el porcentaje de agua abierta y de agua abierta + pantanos de espadañas dentro de un radio de forrajeo de 400 m.

Information on the habitat associations of larval fishes in Great Lakes coastal wetlands (GLCW) is necessary to assist fisheries managers in the protection and management of critical habitats. Coastal wetlands serve as spawning grounds, nurseries, and forage areas for many important Great Lakes fish species. To determine the distribution of larval fish in coastal wetlands with regard to location and vegetation characteristics, we used a larval tow-sled to sample four macrohabitat types (sand-spit, inner and outer marsh, and river) across sparse, moderate, and dense vegetation densities (microhabitat) in Allouez Bay wetland near Lake Superior's western end. We captured 4,806 larval fish representing 16 species between May and August 1996. Allouez Bay is typical of other GLCW in species number and composition. The three most abundant species were spottail shiner (59% of the total catch), yellow perch (20% of total catch), and white sucker (10% of total catch). Significantly more fish and fish species (repeated-measures ANOVA) (p < 0.05) were caught at the sand-spit relative to the outer or inner marsh macrohabitats. Nearly all of the cyprinids and centrarchids were caught at the sand-spit habitat primarily in dense vegetation, while the majority of white suckers and trout-perch were caught in the river in sparse or moderate vegetation. Our study provides evidence for species-specific macrohabitat and microhabitat associations of larval fish in coastal wetlands. We suggest these associations are largely determined by adult spawning requirements and life-history strategies.

Context Significant barriers exist in the delivery of state-of-the-art cancer care to rural populations. Rural providers' knowledge and practices, their rural health care delivery systems, and linkages to cancer specialists are not optimal; therefore, rural cancer patient outcomes are less than achievable. Purpose To test the effects of a strategy targeting rural providers and their practice environment on patient travel for care, satisfaction, economic barriers, and health-related quality of life. Methods A group-randomized trial was conducted with 18 rural communities in the north-central United States. Twelve of these communities were included and defined as the unit of analysis for the patient outcomes portion of the study. The intervention targeted rural providers and their practice environment. The subjects were patients with breast, colorectal, lung, and prostate cancers from the rural communities. The main outcomes were patients' travel to obtain health care, satisfaction with care, perceptions of economic barriers to care, and health-related quality of life. In total, 881 patients were included. Results Group randomization was balanced. Travel for health care was significantly reduced in the community group exposed to the intervention during months 13 to 24 following cancer diagnosis. The mean miles traveled per patient were 1,326 (SE = 306) for the experimental group and 2,186 (SE = 347) for the control group (P = 0.03). No significant differences in satisfaction with care, economic barriers to care, or health-related quality of life were found. Conclusions The intervention significantly reduced cancer patient travel for health care, which suggests that access to care improved in the experimental group. The results of this study do not allow conclusion that there was no effect on other patient outcomes. The results supported the study's conceptual framework and many of its hypotheses.

One of the tasks faced by undergraduate mathematics departments is placing incoming students into the appropriate mathematics classes for their abilities. This is often accomplished through giving a placement test at the time of student orientation. Dissatisfaction with the results of the placement test used at our university prompted us to write a new one. In this paper, we describe the writing of the new placement test and provide detailed results of a validity study on the test. Our results led us to conclude that placement testing does not work very well, and to suggest that undergraduate mathematics departments consider using existing data rather than give a separate placement test. In spite of this conclusion, we do decide to continue with our placement test, and we offer reasons for doing so. *The authors are indebted to David Frisbie, a testing and measurement professor at the University of Iowa, who read early versions of this paper, and gave expert advice. We also thank our colleague, D...

Summary. An exact conditional test for an M-way log-linear interaction in a fully observed 2M contingency table is formulated. Prom this is derived a procedure for interval estimation of the total count N in a 2 M contingency table, one of whose entries is unobserved. This procedure has an immediate application to interval estimation of the size of a closed population from incomplete, overlapping lists of records, as in capture-recapture analysis of epidemiological data. Data on the prevalence of spina bifida in live births in upstate New York in 1969–1974 illustrate this application.

Public health nurses (PHNs) can play an important role in the detection of domestic violence. This study examines whether the introduction of a domestic violence assessment protocol by public health nurses in a maternal and child health visiting program increases the identification and referral rates of women experiencing domestic violence. Data collected from case files during the baseline year prior to the initiation of the protocol were compared to case file information after the protocol had been implemented. When the protocol was used, there was a higher rate of identification, although the difference was not statistically significant. Significantly more women, however, were provided with information about domestic violence resources after the protocol was in place, and significantly more women were referred to services in the second year after the protocol had been implemented. This study provides support for the use of a domestic violence protocol to improve the public health nursing response to domestic violence.

Some individuals of the mixed group of “lean” littermates (+/ ob and +/+) of (C57BL/6J ob/ob) often suggest phenotypic characteristics of ob/ob animals. Therefore, it was of interest to determine whether expression of the ob gene had physiological significance in +/ ob animals. Body weight (BW), fasting blood glucose (FBG), and body core temperature (Tr) were monitored between 62 and 364 days of age in +/+ and +/ obmice. Among females but not males, +/ ob mice were heavier ( P = 0.003) and FBG levels were greater ( P = 0.04) than in +/+ animals. Comparison of Trindicated differences suggesting falling Tr in +/ ob but rising Tr in +/+ mice with age in males but not females. Multivariate analysis of variance yielded genotype effects for both males ( P = 0.002) and females ( P = 0.02). BW, FBG, and Tr alone were sufficient at the 75% level for genotypic characterization and separation of +/? animals as +/ ob or +/+; clearly, expression of the ob gene in heterozygotes of the +/ ob animal may make the mixed +/? group inappropriate as lean controls.

We completed an integrated, 6–year study on the potential ecological effects of two mosquito control agents, methoprene (applied as AltosidTM sand granules) and Bacillus thuringiensis var. israelensis (Bti, applied as Vectobac-GTM granules), on zooplankton, insects, and breeding birds in wetlands of central Minnesota, USA, from 1988 to 1993. The study was a before-and-after design with pretreatment (1988-1990) and posttreatment (1991–1993) of 27 wetlands. Study sites were randomly selected and placed within one of three groups of sites, nine control, nine Bti-treated, and nine methoprene-treated. Selected populations of zooplankton, insects, and breeding birds were sampled within each of these wetlands. Insect densities were reduced by 57 to 83% and biomass was reduced by 50 to 83% in the second (1992) and third (1993) years of treatment. No negative effects on zooplankton or breeding birds could be attributed to treatment or changes to insect communities. Many factors may explain the lack of effects on breeding birds including, reductions in insects occurred after the nesting season was over, nest loss rates due to predation were very high (70%) and may have been a greater limiting factor to birds than mosquito control, and the density of breeding birds may be below carrying capacities, especially because not all wetlands in the landscape were treated and sufficient food may have been available. It is unclear what the long-term consequences of insect reductions mean to wetland health. The lack of close coupling between zooplankton, insects, and breeding birds probably reflects the ecological complexity of these wetlands such as the presence of other limiting factors on population distribution and abundance. Although the study period was relatively long (3 years of treatment) compared with most ecological studies of pesticides, it may not have been long enough to fully predict the effects of decades of continued mosquito control.

We studied the effects of the mosquito larvicides methoprene and Bacillus thuringiensis israelensis (Bti) on the benthic macroinvertebrate communities of 27 wetland ecosystems in Wright County, Minnesota. These larvicides are generally considered safe for nontarget species. After 3 yr of preliminary investigations, including 2 yr of intensive sampling, larvicide treatments were applied during 1991–1993. Nine of the wetlands were experimentally treated with methoprene, which disrupts insect development; an additional set of nine wetlands were treated with Bti, a microbial larvicide; and nine wetlands were left untreated to serve as a control treatment. In general, insecticide treatment had minimal effects on nontarget groups during the first treatment year. However, during 1992, highly significant reductions due to both methoprene and Bti were observed in several insect groups. Predatory insects were reduced on methoprene-treated sites but not Bti-treated sites in 1992. In 1993, treatment with both larvicides resulted in wetland communities that were depauperate in most insects. Although effects were observed broadly across insect taxa, Diptera, which comprised 79% of the insects, were affected most strongly, especially the dipteran suborder Nematocera, which included 71% of total insects and was dominated by Chironomidae. Minimal effects on noninsect macroinvertebrates were observed. Bti- and methoprene-treated sites also showed a reduction in richness of insect genera and an increased tendency to be dominated by one or a few genera. Pretreatment data, collected under drought conditions from the same wetlands, showed that the benthic macroinvertebrate fauna was dominated by mollusks during the drought but became increasingly dominated by insects during the wetter years. On the treated sites, insects remained at low density, very similar to the drought conditions, but the noninsect macroinvertebrates declined on treated sites in the same pattern as on control sites. Both indirect effects and direct toxicity likely contributed to the observed differences. Bti is likely to be directly toxic only to nematoceran Diptera; thus effects of Bti on other insect groups may have resulted from disruption of the invertebrate food web. Methoprene is more broadly toxic; thus observed methoprene effects on nonnematoceran groups may have been due to either direct toxicity or food web effects, or both. The 2–3 yr lag time in response of nontarget insects to larvicide treatment demonstrates the need for long-term studies in wetland ecosystems, and the need to reconsider the conclusions based on previous short-term studies that these larvicides are environmentally safe.

Log-linear models for capture-recapture type data are widely used for estimating sizes of populations. Log-linear methods model conditional interactions between the sources. Often, however, the marginal associations are more appropriate and easier for the practitioner to conceptualize. Analyses here of previously published data on cases of spina bifida in upstate New York are used to show how the assumption that sources are conditionally independent can give biased estimates if in fact the sources are marginally independent. A plausible model for the structural sources of interactions between the sources of information about spina bifida cases is developed which implies marginal independence of two of the sources rather than conditional independence. Estimates of the population total based on marginal independence are derived and give larger estimates of the population total than those derived based upon conditional dependence. When investigators can in fact model the likely underlying relationships of the sources in the population, we suggest considering modelling the potential interdependencies of the sources, which we term 'structural source modeling'.

We examined the possible effects of mosquito control treatments of wetlands withBacillus thuringiensis israelensis (Bti, applied as Vectobac-G granules) and methoprene (applied as Altosid sand granules) on wetland breeding bird communities. Data collected two years before (1988 and 1990) were compared to data collected three years after (1991–1993) treatments were applied. Total numbers of species and individuals observed remained relatively constant throughout the study period, but several individual species varied annually, most likely due to changes in water levels and habitat available. We found no effect of Bti or methoprene treatments on the bird community or on 19 individual bird species. The few differences that were observed between control and treatment were inconsistent over time and were likely due to chance because of the large number of comparisons that were completed. Despite relatively large reductions of aquatic insects (including mosquitoes) in mid- to late-summer following both treatments types, it is unlikely that food available to bird species in these wetlands was depressed during the breeding season. Effects of weather and predation were probably more important influences on species and community parameters than was mosquito control treatment during the study period. Because of lower aquatic insect densities in midto late-summer, other parts of the avian life cycle such as late summer survival, dispersal of young birds, or migrating birds may be more affected by mosquito control treatments.

The authors propose a method for adjusting results of log-linear multi-source capture-recapture estimates of total population. The method compares the totals in some subpopulations of known size with estimates derived from various capture-recapture approaches to these subpopulations. The authors term such an approach an "internal validity analysis". Trends in the ratios of the estimates to the known true values of these subpopulations provide a plausible indicator of the bias of some types of estimates of the total population especially when underlying assumptions of the methods used have not been met in analysis of the total population. The authors apply this method to published data on an open population of injection drug users that had been previously analyzed with a standard capture-recapture analysis as if it were a closed population. Internal validity analysis suggests that the size of this population is about 15% greater than that previously estimated.

The physiological effects of episodic pH fluctuations on Atlantic salmon Salmo salar smolts in eastern Maine, U.S.A., were investigated. During this study, S. salar smolts were exposed to ambient stream-water chemistry conditions at nine sites in four catchments for 3 and 6 day intervals during the spring S. salar smolt migration period. Plasma chloride, plasma glucose, gill aluminium and gill Na(+)- and K(+)-ATPase levels in S. salar smolts were assessed in relation to ambient stream-water chemistry during this migration period. Changes in both plasma chloride and plasma glucose levels of S. salar smolts were strongly correlated with stream pH, and S. salar smolt mortality occurred in one study site with ambient stream pH between 5·6 and 5·8 during the study period. The findings from this study suggest that physiological effects on S. salar smolts are strongly correlated with stream pH and that in rivers and streams with low dissolved organic carbon (DOC) concentrations the threshold for physiological effects and mortality probably occurs at a higher pH and shorter exposure period than in rivers with higher DOC. Additionally, whenever an acidification event in which pH drops below 5·9 coincides with S. salar smolt migration in eastern Maine rivers, there is potential for a significant reduction in plasma ions of S. salar smolts.

If tau d is the relative risk of a disorder in the entire population, and tau d,i is the relative risk of the disorder in i = 1, ... m strata, then one may show readily that tau d = sigma ci tau d,i, where ci is the product of two terms tau i, the risk ratio of being in the ith stratum, and pi,unexp d, the proportion of those with the disorder and unexposed who are in the ith stratum. This formulation is of primary interest in epidemiology when relative risks are available on one or only some strata of a variable that itself may be affected by exposure (what one may define as a "susceptible" covariate) such as mortality or hospitalization. Although relative risks within strata of such a variable may be of some intrinsic clinical interest, only the risk ratio unstratified on such a variate may be pertinent to a causal effect (unlike the case for nonsusceptible variables such as sex, age, etc). In some instances, as for birth defects, one may have data from a few strata or only one (for example, livebirths) of a susceptible covariate (for example, conceptus viability). But one may still be able to draw useful inferences about tau d, the risk ratio in the entire population, because if tau d,i > or = 1/ci (or k/ci), one may conclude that tau d is, at least, greater than 1.0 (or k). Similarly, a study of a disorder limited to hospitalized cases and controls may enable investigators to infer, using the same criterion, a positive association in the entire population despite the presence of hospitalization bias of the type described by Berkson.

One may express the relative risk of defect in all conceptuses, r(def), as a function of the relative risk of defect in livebirths, r(def,lb), and in embryonic and fetal deaths, r(def,efd), as r(def) = C(lb)r(def,lb) + C(efd)r(def,efd), where C(lb) and C(efd) are coefficients defined in terms of conceptus and defect viability and lethality. If the relative risk of birth defect in livebirths, r(def,lb), is greater than unity, but the relative risk of defect in all conceptuses, r(def), is equal to or less than unity (or the reverse pattern holds), then the relative risk of defects in livebirths may be said to be "distorting" or "misrepresentative" because it does not reflect the nature of the association in all conceptuses. The authors define and present an explicit expression for a boundary upon the relative risk of defect in livebirths. If the relative risk of defect in livebirths is (validly) greater than this boundary value, then the relative risk in all conceptuses must be greater than unity and the observed relative risk of defect in births is "representative" and not distorting. The authors show that the boundary value is equal to 1/C(lb), where C(lb) is a simple function of the lethality of all unexposed conceptuses, the lethality of unexposed conceptuses with defect, and the relative risk of any embryonic and fetal death. Tables of the boundary relative risk for various values of these variables are presented. Over a very wide range of reference variables, a (valid) relative risk of defect in livebirths of 3.5 or greater implies a positive association with defect in all (recognized) conceptuses in the population studied.

See related article, p 346–352 Preeclampsia is a devastating pregnancy-specific condition that can result in adverse maternal or fetal outcomes, including preterm delivery, very low birth weight, or maternal–fetal demise. In addition, preeclampsia is a heterogeneous multisystem disorder, with simple defining symptoms that do not adequately represent the complex nature of the syndrome. The clinical presentation of preeclampsia is often secondary to one or more maternal risk factors, such as obesity, advanced maternal age, or history of hypertension at the onset of pregnancy. Given the increasing prevalence of these risk factors in the general population, the rates of preeclampsia are likely to continue rising in the coming years. Preeclampsia is often considered in 2 discrete phases: (1) a silent stage of abnormal placental development and function with no overt symptoms and (2) a symptomatic stage of endothelial dysfunction, hypertension, and abnormal cardiorenal function likely because of excess production of circulating inflammatory and vasoactive factors, largely of placental origin. To this end, there has been a significant interest in identifying factor(s) that presage clinical onset of the disease and prove useful as biomarkers or therapeutic targets. Molecules that have captured the attention of basic and clinical researchers in recent years are the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and the proangiogenic placental growth factor (PlGF) and vascular endothelial growth factor. The hypothesis that an imbalance in pro- and antiangiogenic factors plays an important role in the pathophysiology of preeclampsia was initially championed by …

Synthetic and natural steroidal androgens and estrogens and many other non-steroidal endocrine-active compounds commonly occur as complex mixtures in aquatic environments. It is important to understand the potential interactive effects of these mixtures to properly assess their risk. Estrogen receptor agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little is known, however, concerning possible mixture interactions of androgen receptor agonists. In these studies we used the MDA-kb2 cell line, a human breast cancer cell line with endogenous androgen receptors and a stably transfected luciferase reporter gene construct to quantify the androgenic activity of seven natural and synthetic androgens: 17β-trenbolone, dihydrotestosterone, methyltestosterone, testosterone, trendione, 17α-trenbolone, and androstenedione. We tested combinations of these androgens and compared the observed activity to expected androgenic activity based on a concentration addition model. Our analyses support the hypothesis that androgen receptor agonists cause additive responses in a mixture. Binary mixtures of 17β-trenbolone with 17β-estradiol or triclocarban (an anti-microbial found in the environment) were also tested. 17β-Estradiol induced androgenic activity, but only at concentrations 600-fold greater than those found in the environment. Triclocarban enhanced the activity of 17β-trenbolone. Additionally, three anti-androgens were each paired with three androgens of varying potencies. The relative potencies of the antagonists were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the androgen used. The results of our studies demonstrate the potential utility of the androgen-responsive MDA-kb2 cell line for quantifying the activity of mixtures of endocrine-active chemicals in complex wastes such as municipal effluents and feedlot discharges. Environ. Toxicol. Chem. 2010;29:1367–1376. © 2010 SETAC

NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

Almost all reported prevalence studies of which we are aware make exhaustive attempts to find diagnosed individuals and report all affected individuals, but make no attempt to estimate or adjust for missing cases. Yet very simple methods introduced in the planning stage of a prevalence study may enable investigators, or at least those subsequently reading their reports, to derive such adjusted estimates. If investigators keep track of the nature of the ascertainment of cases by source and collect and report data that allow calculation of the number of cases by source intersection, then they, or at least others, may derive estimates of missing cases and of the total population affected, by using readily available analogues of capture-recapture methods developed for wildlife populations censuses. Unfortunately, such methods are often inappropriately disparaged or ignored by epidemiologists. The derived estimates are sensitive to assumptions about dependence or independence ("interaction") of various sources, assumptions that sometimes are unprovable, and these estimates have some uncertainty because of statistical fluctuation. Moreover, most investigators who attempt exhaustive prevalence studies apparently believe that they have ascertained all cases and that there is no need to attempt to adjust for, let alone provide data pertinent to, the number of missing cases or to use a statistical method that will at best imply a certain imprecision to their result. Yet a survey that reports prevalence data without adjustment for, or data on, source intersection in essence makes an estimate of missing cases--zero--while providing no quantitative grounds for that claim. The results of all such surveys should be regarded with skepticism because, at best (if the case reports are accurate), they provide only a lower boundary of prevalence. We illustrate the grounds for these views by analyzing data from an apparently exhaustive prevalence study that used at least 14 distinct sources for ascertainment, including advertising, to find cases. Available limited data on source intersection provided in the report enable the plausible inference that the study missed about 25-40% of cases. We urge that no attempted complete prevalence studies be presented without data on ascertainment by source intersection.

Although many estrogen receptor–positive (ER+) breast cancers are effectively treated with selective estrogen receptor modulators and down-regulators (SERM/SERD), some are highly resistant. Resistance is more likely if primary cancers are devoid of progesterone receptors (PR−) or have high levels of growth factor activity. In this study, a transgenic mouse line that expresses transforming growth factor-α (NRL-TGFα mice) and that develops ER+/PR− mammary tumors was used to assess the possible effects of (a) therapeutic delivery of the SERM, tamoxifen, or SERD, ICI I82,780 (ICI), on the growth of established tumors and (b) short-term prophylactic tamoxifen administration on the initial development of new mammary tumors. To determine the therapeutic effects of tamoxifen and ICI on the growth of established tumors, mice were exposed to 3 weeks of drug treatment. Neither drug influenced tumor growth or glandular pathology. To determine if early prophylactic tamoxifen could alter tumorigenesis, a 60-day tamoxifen treatment was initiated in 8-week-old mice. Compared with placebo-treated mice, tamoxifen reduced tumor incidence by 50% and significantly decreased the degree of mammary hyperplasia. Prophylactic tamoxifen also significantly extended the life span of tumor-free mice. These data show that in this mouse model, established ER+/PR− mammary tumors are resistant to SERM/SERD treatment but the development of new mammary tumors can be prevented by an early course of tamoxifen. This study validates the utility of NRL-TGFα mice for (a) identifying candidate biomarkers of efficacious tamoxifen chemoprevention and (b) modeling the evolution of tamoxifen resistance.

The objective of this study was to develop and use HPLC based analytical methodology to characterize nucleosides in blood plasma and serum from fish with and without tumors, with a goal of determining if fish blood nucleoside concentrations could similarly be used as a bioindicator of tumor development in fish. The approach was to develop analytical methodology and quality assurance criteria for the analysis of nucleosides in fish blood, and to characterize nucleoside concentrations in blood of fish for which both healthy and tumor-bearing samples were available. Data would then be used to establish parameters with which tumor-bearing fish could be distinguished from healthy fish. Blood samples used to establish the diagnostic parameters were from control rainbow trout (Oncorhynchus mykiss) and those with tumors developed after exposure to aflatoxins. A second set of blood samples was from field collected black bullheads (Ictalurus melas).

One encounters in the literature estimates of some rates of genetic and congenital disorders based on log-linear methods to model possible interactions among sources. Often the analyst chooses the simplest model consistent with the data for estimation of the size of a closed population and calculates confidence intervals on the assumption that this simple model is correct. However, despite an apparent excellent fit of the data to such a model, we note here that the resulting confidence intervals may well be misleading in that they can fail to provide an adequate coverage probability. We illustrate this with a simulation for a hypothetical population based on data reported in the literature from three sources. The simulated nominal 95 per cent confidence intervals contained the modelled population size only 30 per cent of the time. Only if external considerations justify the assumption of plausible interactions of sources would use of the simpler model's interval be justified.

Previous studies in a guinea pig model of asthma have suggested that age and sex contribute both to the profile of asthma symptoms, i.e., asthma heterogeneity, as well as to the success of primary prevention strategies. The present study investigated the contributions of age and sex to the severity of central vs. peripheral airway hyperresponsiveness as well as to the effectiveness of secondary preventions strategies for asthma as modeled in the guinea pig. Experimental groups: Young/Young, sensitized and challenged before sexual maturity; Young/Adult, sensitized young and challenged after sexual maturity; Adult/Adult, sensitized and challenged after sexual maturity. Males and females were sensitized IP with 0.5 mg/kg ovalbumin (OVA) and challenged intratracheally with varying doses of OVA. Cellular infiltration into lung and lavage fluid, OVA specific IgG(1) as well as airway hyperresponsiveness to intravenous methacholine were determined 24 hr later. Airway hyperresponsiveness in central airways and peripheral lung was assessed by measurement of airway resistance, tissue damping and tissue elastance. Airway hyperresponsiveness with allergen sensitization and challenge was evident in male and female Adult/Adult animals and male Young/Young animals. Airway hyperresponsiveness in female Young/Young animals was not significant, despite marked airway eosinophilia. Changes in tissue elastance were more evident in OVA treated Adult/Adult compared to Young/Young animals. As allergen exposure decreased, a reduction in inflammation was seen in young females before other age sex groups. OVA induced increases in eosinophils were more pronounced in Young/Adult compared to Adult/Adult animals. Our results suggest that in asthmatic children, females may clinically benefit most from secondary prevention strategies to limit allergen exposure. In adult asthmatics, changes in tissue elastance may be significant, and secondary prevention strategies may be more effective in those sensitized as children compared to those sensitized as adults.

A better understanding of relationships between human activities and water chemistry is needed to identify and manage sources of anthropogenic stress in Great Lakes coastal wetlands. The objective of the study described in this article was to characterize relationships between water chemistry and multiple classes of human activity (agriculture, population and development, point source pollution, and atmospheric deposition). We also evaluated the influence of geomorphology and biogeo- graphic factors on stressor-water quality relationships. We collected water chemistry data from 98 coastal wetlands distributed along the United States shoreline of the Lau- rentian Great Lakes and GIS-based stressor data from the associated drainage basin to examine stressor-water quality relationships. The sampling captured broad ranges (1.5-2 orders of magnitude) in total phosphorus (TP), total nitro- gen (TN), dissolved inorganic nitrogen (DIN), total suspended solids (TSS), chlorophyll a (Chl a), and chlo- ride; concentrations were strongly correlated with stressor metrics. Hierarchical partitioning and all-subsets regression analyses were used to evaluate the independent influence of different stressor classes on water quality and to identify best predictive models. Results showed that all categories of stress influenced water quality and that the relative influence of different classes of disturbance varied among water quality parameters. Chloride exhibited the strongest relationships with stressors followed in order by TN, Chl a, TP, TSS, and DIN. In general, coarse scale classification of wetlands by morphology (three wetland classes: riverine, protected, open coastal) and biogeography (two ecopro- vinces: Eastern Broadleaf Forest (EBF) and Laurentian Mixed Forest (LMF)) did not improve predictive models. This study provides strong evidence of the link between water chemistry and human stress in Great Lakes coastal wetlands and can be used to inform management efforts to improve water quality in Great Lakes coastal ecosystems.