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Speckle tracking echo is a useful clinical tool to distinguish differential RV contractility between PAH subtypeshttp://ow.ly/6Wyr30fVTeu

The factors that impact the clinical effectiveness of bare nitinol stents in claudicants with symptomatic femoropopliteal atherosclerosis are incompletely known. The authors analyzed variables that may influence stent durability and provide a benchmark for their effectiveness. Data analyzed from six studies (999 patients) included baseline noninvasive hemodynamic tests, angiographic characteristics, ultrasound defined stent patency and target lesion revascularization through 12-months. Baseline ankle-brachial index and lesion length predicted stent patency and target lesion revascularization and when combined interacted significantly to better predict outcomes. This meta-analysis provides an important comparator against which emerging therapies that treat claudicants with femoropopliteal atherosclerosis can be assessed.Peripheral Artery Disease BACKGROUND: The performance of bare metal nitinol stents in patients with symptomatic femoropopliteal peripheral artery disease (PAD) is not well defined.Patient-level data from six large prospective trials sponsored by medical device manufacturers was abstracted and analyzed to identify a cohort of patients with claudication and femoropopliteal artery occlusive disease. Twelve-month binary patency and target lesion revascularization (TLR) rates were primary outcomes. Stent patency was assessed by duplex ultrasonography (DUS) and TLR was a clinically driven intervention. To characterize the effects of patient characteristics on the outcomes, meta-regression was performed via mixed effects logistic regression models with patient-level covariates.About 999 patients were analyzed; the mean ABI was 0.68 ± 0.18, the mean lesion length was 84 ± 53 mm, the mean lesion stenosis was 78%, and nearly two thirds of patients had mild to severe calcification. The mean Rutherford clinical category was 2.7 ± 0.6 and ranged from 2.6 to 2.8 in all studies. The 12-month patency across all studies was 69.8% and TLR rates ranged from 9.2% to 19.7%. Multivariable analysis demonstrated that baseline ABI and baseline target lesion length predicted both primary patency and TLR. Further, these two variables interacted significantly to better predict TLR outcomes when used in combination.The 12-month clinical effectiveness of bare nitinol stents to treat patients with symptomatic femoropopliteal PAD is acceptable and is impacted by clinical and lesion-specific characteristics. These data provide an important and useful benchmark to compare the clinical benefit of emerging endovascular PAD therapies. © 2017 Wiley Periodicals, Inc.

Pulmonary arterial hypertension (PAH) commonly complicates systemic sclerosis (SSc) and is a leading cause of death in this patient population. While advances in our understanding of the pathobiology of PAH have led to novel therapies directed at PAH, response to these agents in patients with PAH related to SSc (SSc-PAH) has in general been less robust than in patients with other forms of PAH. The reasons for these differences in response to therapy between SSc-PAH and other PAH patients are complex, but likely include the outcome measure selected to assess response (e.g., the 6-min walk test and hospitalizations) and concomitant diseases that influence response (e.g., gastrointestinal dysmotility and renal dysfunction), among others. In this chapter, we present a patient vignette to highlight the challenges in management of SSc-PAH and to offer our practice pattern to address these challenges.

This study measured part of the in-hive pesticide exposome by analyzing residues from live in-hive bees, stored pollen, and wax in migratory colonies over time and compared exposure to colony health. We summarized the pesticide burden using three different additive methods: (1) the hazard quotient (HQ), an estimate of pesticide exposure risk, (2) the total number of pesticide residues, and (3) the number of relevant residues. Despite being simplistic, these models attempt to summarize potential risk from multiple contaminations in real-world contexts. Colonies performing pollination services were subject to increased pesticide exposure compared to honey-production and holding yards. We found clear links between an increase in the total number of products in wax and colony mortality. In particular, we found that fungicides with particular modes of action increased disproportionally in wax within colonies that died. The occurrence of queen events, a significant risk factor for colony health and productivity, was positively associated with all three proxies of pesticide exposure. While our exposome summation models do not fully capture the complexities of pesticide exposure, they nonetheless help elucidate their risks to colony health. Implementing and improving such models can help identify potential pesticide risks, permitting preventative actions to improve pollinator health.

Agrochemical risk assessment that takes into account only pesticide active ingredients without the spray adjuvants commonly used in their application will miss important toxicity outcomes detrimental to non-target species, including humans. Lack of disclosure of adjuvant and formulation ingredients coupled with a lack of adequate analytical methods constrains the assessment of total chemical load on beneficial organisms and the environment. Adjuvants generally enhance the pesticidal efficacy and inadvertently the non-target effects of the active ingredient. Spray adjuvants are largely assumed to be biologically inert and are not registered by the USA EPA, leaving their regulation and monitoring to individual states. Organosilicone surfactants are the most potent adjuvants and super-penetrants available to growers. Based on the data for agrochemical applications to almonds from California Department of Pesticide Regulation, there has been increasing use of adjuvants, particularly organosilicone surfactants, during bloom when two-thirds of USA honey bee colonies are present. Increased tank mixing of these with ergosterol biosynthesis inhibitors and other fungicides and with insect growth regulator insecticides may be associated with recent USA honey bee declines. This database archives every application of a spray tank adjuvant with detail that is unprecedented globally. Organosilicone surfactants are good stand alone pesticides, toxic to bees, and are also present in drug and personal care products, particularly shampoos, and thus represent an important component of the chemical landscape to which pollinators and humans are exposed. This mini review is the first to possibly link spray adjuvant use with declining health of honey bee populations.

This article examines measures of student success, with a focus on how they apply to community colleges. A conceptual framework is presented as a way of facilitating thinking about and accurately grounding discussions of student success. The article closes with an examination of emerging concepts related to the measurement of student success in higher education generally and at community colleges particularly.

In patients with heart disease, diabetes and age predict adverse outcomes. It remains unclear whether persons with diabetes who have implantable cardioverter defibrillators (ICDs) have fewer appropriate and inappropriate ICD shocks. The objective of this study is to determine if persons with diabetes who have ICDs receive a similar amount of appropriate and inappropriate shocks compared to persons without diabetes. In a post hoc analysis of 1,528 patients enrolled in the INTRINSIC RV trial, all-cause mortality and ICD shocks between persons with and without diabetes, stratified by age, was compared. The relationship between shock and mortality was also assessed. Mortality 1 year after ICD implant was lower for persons without diabetes vs. persons with diabetes (3.5% vs. 7.9%, p < 0.001). Young and old persons with diabetes received a similar number of total and appropriate ICD shocks. However, older persons with diabetes were less likely to receive inappropriate ICD shocks vs. older persons without diabetes (1.9% vs. 6.9%, p < 0.01). ICD shocks were not temporally related to mortality regardless of diabetes status. In the INTRINSIC RV trial, persons with diabetes and older persons without diabetes undergoing ICD implant were at a higher risk of death. Older persons with diabetes received less inappropriate shocks and still had a similar amount of appropriate shocks compared to persons without diabetes of similar age.

Colony collapse disorder (CCD), a syndrome whose defining trait is the rapid loss of adult worker honey bees, Apis mellifera L., is thought to be responsible for a minority of the large overwintering losses experienced by U.S. beekeepers since the winter 2006-2007. Using the same data set developed to perform a monofactorial analysis (PloS ONE 4: e6481, 2009), we conducted a classification and regression tree (CART) analysis in an attempt to better understand the relative importance and interrelations among different risk variables in explaining CCD. Fifty-five exploratory variables were used to construct two CART models: one model with and one model without a cost of misclassifying a CCD-diagnosed colony as a non-CCD colony. The resulting model tree that permitted for misclassification had a sensitivity and specificity of 85 and 74%, respectively. Although factors measuring colony stress (e.g., adult bee physiological measures, such as fluctuating asymmetry or mass of head) were important discriminating values, six of the 19 variables having the greatest discriminatory value were pesticide levels in different hive matrices. Notably, coumaphos levels in brood (a miticide commonly used by beekeepers) had the highest discriminatory value and were highest in control (healthy) colonies. Our CART analysis provides evidence that CCD is probably the result of several factors acting in concert, making afflicted colonies more susceptible to disease. This analysis highlights several areas that warrant further attention, including the effect of sublethal pesticide exposure on pathogen prevalence and the role of variability in bee tolerance to pesticides on colony survivorship.

Until 1985 discussions of pesticides and honey bee toxicity in the USA were focused on pesticides applied to crops and the unintentional exposure of foraging bees to them. The recent introduction of arthropod pests of honey bees, Acarapis woodi (1984), Varroa destructor (1987), and Aethina tumida (1997), to the USA have resulted in the intentional introduction of pesticides into beehives to suppress these pests. Both the unintentional and the intentional exposure of honey bees to pesticides have resulted in residues in hive products, especially beeswax. This review examines pesticides applied to crops, pesticides used in apiculture and pesticide residues in hive products. We discuss the role that pesticides and their residues in hive products may play in colony collapse disorder and other colony problems. Although no single pesticide has been shown to cause colony collapse disorder, the additive and synergistic effects of multiple pesticide exposures may contribute to declining honey bee health.

Aims This retrospective analysis sought to develop and validate a model using the measured diagnostic variables in cardiac resynchronization therapy (CRT) devices to predict mortality. Methods and results Data used in this analysis came from two CRT studies: Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices (CRT RENEWAL) ( n = 436) and Heart Failure-Heart Rate Variability (HF-HRV) ( n = 838). Patients from CRT RENEWAL were used to create a model for risk of death using logistic regression and to create a scoring system that could be used to predict mortality. Results of both the logistic regression and the clinical risk score were validated in a cohort of patients from the HF-HRV study. Diagnostics significantly improved over time post-CRT implant (all P < 0.001) and were correlated with a trend of decreased risk of death. The regression model classified CRT RENEWAL patients into low (2.8%), moderate (6.9%), and high (13.8%) risk of death based on tertiles of their model predicted risk. The clinical risk score classified CRT RENEWAL patients into low (2.8%), moderate (10.1%), and high (13.4%) risk of death based on tertiles of their score. When both the regression model and the clinical risk score were applied to the HF-HRV study, each was able to classify patients into appropriate levels of risk. Conclusion Device diagnostics may be used to create models that predict the risk of death.

Introduction: Due to limited enrollment of women in previous trials, there is a paucity of data comparing outcome and arrhythmic events in men versus women with implantable cardioverter defibrillators (ICDs). Methods and Results: We analyzed outcome of patients in the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs) trial based on gender. Women comprised 19% (293/1530) of the INTRINSIC RV population. Compared with men, women were less likely to have coronary disease, ischemic cardiomyopathy, and hyperlipidemia, and were more likely to have congestive heart failure and diabetes. Women were less likely to receive beta blockers and ACE inhibitors, and more likely to receive diuretics. Over 10.8 ± 3.5 months of follow-up, unadjusted mortality was higher in women than men (6.8% vs 4.1%, P = 0.04). Heart failure hospitalizations occurred in 7.9% of women versus 5.7% of men (P = 0.13). After adjustment for baseline differences and drug therapy, there was no significant difference in mortality between men and women. Adverse events were observed more often in women. There were no gender differences in the percentage of patients receiving appropriate or inappropriate ICD shocks. Conclusions: In INTRINSIC RV, women receiving ICDs differed from men regarding baseline characteristics and drug therapy. After adjusting for baseline differences and medical therapy, there were no differences in heart failure hospitalization, survival, or ICD shock therapy during follow-up. Apparent undertreatment of heart failure and greater frequency of adverse advents in women receiving ICDs warrant further investigation.

We present the strong fluorescence effect, a new 392 nm emission peak appearing after binding of a naphtol-urea inhibitor XIIa to the enzyme epoxide hydrolase (EH), along with the quenching of the EH tryptophan fluorescence. We have studied the quenching of the 392-nm peak (attributed to XIIa bound inside the active center of the enzyme) of the mixture EH +XIIa by various strong transparent inhibitors (competing with XIIa for binding to EH), and measured the corresponding values of the Stern-Volmer constants, K(mix)(SV). Strong EH inhibitors demonstrate different replacement behavior which can be used to distinguish them. We further demonstrate a novel fluorescent assay which allows to distinguish highly potent inhibitors and to visualize the strongest among them. We generated our assay calibration curve based on the quenching data, by plotting quenching strength K(mix)(SV) versus inhibiting strength, IC(50) values. We used moderate inhibitors for the assay plot generation. We then applied this curve to determine IC(50) values for several highly potent inhibitors, with IC(50) values at the limit of the IC(50) detection sensitivity by colorimetric enzyme assay. IC(50) values determined from our quenching assay show correlation with IC(50) values determined in the literature by more sensitive radioactive-based assay and allow differentiating the inhibitors potency in this group. To our knowledge, this is the first inhibitor assay of such kind. Chemical inhibition of EH is an important technology in the treatment of various cardiovascular diseases, therefore, this tool may play a crucial role in discovering new inhibitor structures for therapeutic EH inhibition.

Insecticidal Bt crops and seed treatments represent additional pest management tools for growers, prompting ecological studies comparing their impact on farm system inputs and effects to nontarget organisms compared with conventional practices. Using high taxonomic and temporal resolution, we contrast the dominance structure of carabids and dynamics of the most abundant species in maize (both sweet and field corn) agroecosystems using pest management tactics determined by the purchase of seed and application of pyrethroid insecticides. In the seed-based treatments, sweet corn contained Cry1Ab/c proteins, whereas field corn contained the coupled technology of Cry3Bb1 proteins for control of corn rootworm and neonicotinoid seed treatments aimed at secondary soil-borne pests. The insecticide treatments involved foliar pyrethroids in sweet corn and at-planting pyrethroids in field corn. The carabid community, comprised of 49 species, was dominated by four species, Scarites quadriceps Chaudoir, Poecilus chalcites Say, Pterostichus melanarius Illiger, and Harpalus pensylvanicus DeGeer, that each occupied a distinct temporal niche during the growing season. Two species, Pt. melanarius and H. pensylvanicus, exhibited differences between treatments over time. Only H. pensylvanicus had consistent results in both years, in which activity densities in field corn were significantly higher in the control in July and/or August. These results, along with laboratory bioassays, led us to hypothesize that lower adult captures resulted from decrease in prey availability or exposure of H. pensylvanicus larvae to soil-directed insecticides-either the neonicotinoid seed treatment in the transgenic field corn or an at-planting soil insecticide in the conventional field corn.

Collegiate athletic programs have often been referred to as the “front porch”of an institution (Nazarian, 2007). Coaches, athletic teams, student athletes,and athletic department staff serve as a “link between the immediate cam-pus family and the larger community” (p. 4). It is this front-porch principlethat makes managing intercollegiate athletics a unique and challengingendeavor. This chapter gives community college leaders and decision mak-ers a road map for handling situations regarding expansion, elimination, orcontinued maintenance of athletic teams and programs at their institution.Every year, community college athletic programs have an impact onmore than seventy-eight thousand student athletes through sponsorship ofsome two dozen men’s and women’s individual and team sports at morethan 630 institutions in the United States and Canada (Commission on Ath-letics, n.d.; National Junior College Athletic Association, 2008; NorthwestAthletic Association of Community Colleges, n.d.). The presence of an ath-letic program at the community college can generate a sense of belonging,boost student morale and alumni support, increase retention, and positivelyaffect student athletes’ academic success (Ashburn, 2007; Berson, 1996;Rishe, 2003). It is for these reasons that athletics at the community college39

Atrial fibrillation (AF) has been associated with higher rates of all-cause mortality in patients with heart failure (HF). The risk of newly detected AF in patients receiving implantable cardioverter-defibrillator (ICD) therapy is unknown.Newly detected AF was evaluated in all patients enrolled in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) study. The relationships between AF and endpoints (total mortality, ICD shocks, and HF hospitalizations) were analyzed retrospectively with proportional-hazards models.At 108 centers, 1530 patients meeting VITALITY AVT ICD indications were followed for 12 months. Of these, 1356 (89%) had no history of AF at the time of implant. Patients with a history of AF had a higher prevalence of HF (52% vs. 36%; P.01) and had higher rates of HF hospitalization (hazard ratio [HR] 2.14 [1.29-3.54], P.01), death (HR 2.22 [1.26-3.92], P.01), and any ICD shock (HR 1.75 [1.19-2.58], P.01) compared with those with no history. AF incidence during the first 3 months of implant was available in 1317 (86%; 1170 no AF, 147 history of AF) patients. New-onset AF during the first 3 months of implant (45 of 1170, 4%) was associated with a significant increased risk of death (HR 2.86 [1.02-8.05], P = .05) but not with inappropriate ICD shock (HR 2.43 [0.87-6.75], P = .09) or HF hospitalization (HR 1.17 [0.28-4.82], P = .83).History of AF at the time of ICD implant identifies additional risk of HF and death. Newly detected AF is associated with significantly higher rates of death. The relationship between newly detected AF and inappropriate ICD shock or HF hospitalization is uncertain and requires further study.

The purpose of this study was to replicate the analysis made by D. Verstegen and L. Driscoll in The Illinois Dilemma (2008) utilizing the actual allocations to districts resulting from the funding formula in Illinois for the 2004-2005 school year to understand the influence of adjusted values on determinants of fiscal equity. The results of a study by the Illinois Education Research Council (IERC) showed that actual, unadjusted values revealed a more fiscally inequitable system than reported by Verstegen and Driscoll as determined by the calculations traditional to school finance. For example, where Verstegen and Driscoll reported a range per pupil of $16,620 for all districts, IERC found a range of $28,578 per pupil. Illinois' multiple district configurations influenced the analysis. Illinois has three basic types of school districts-elementary, high school, and unit (K-12) districts. Elementary districts, which represent 26.5% of the state's pupil count, contributed the greatest influence on the inequitable findings. Furthermore, IERC's study found ten elementary districts-representing just 0.29% of all pupils in Illinois-had considerable influence on fiscal equity, as evidenced by the range per pupil for all district types dropping to $9,468 from $28,579 when they were excluded from the analysis. The study concludes that researchers must acknowledge the efforts that states employ to address additional funding for populations of interest, that policymakers must insist on both adjusted and unadjusted figures, and that an Illinois-specific and comprehensive report is needed which includes analyses of both General State Aid (the funding formula) and categorical aid which is outside the formula.

This study identified governing state entities charged with the development of a funding formula for community colleges. Analysis of the data revealed that 40 states utilized a funding formula. Twenty-one states had a “Higher Education” entity with governing control of the formula, 5 states had a “Community College” entity with distinct funding formulas for community colleges, funding formulas in 2 states fell under a “Comprehensive (K-20) Education” entity, and in 12 states control of a state funding formula was the responsibility of a state statute. Findings and implications of funding formula governance patterns are discussed.

The increased difference in tuition and fees between public community colleges and undergraduate institutions has increased significantly since 1950, with changes being most distinct in the past decade. The purpose of the study was to determine the relationship of tuition differential between public institution types (TUDI) to governing entities statutorily responsible for the development of tuition and fee policy. In discussing descriptive differences, it was observed that, on average, states' systems were promoting affordable entry points to postsecondary education. This was done via both the lowest prices and the smallest difference in price when compared to other governing entities. Findings and implications were discussed.

Background The effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time and right ventricular (RV) load is unknown. Methods To determine the association of HR and BSA with the pulmonary RC time and measures of RV load, we studied three large patient cohorts including subjects with 1) known or suspected pulmonary arterial hypertension (PAH) (n = 1008), 2) pulmonary hypertension due to left heart disease (n = 468), and 3) end-stage heart failure with reduced ejection fraction (n = 150). To corroborate these associations on an individual patient level, we performed an additional analysis using high-fidelity catheters in 22 patients with PAH undergoing right atrial pacing. Results A faster HR inversely correlated with RC time (p

Community college funding formulas are tools utilized to substantiate the acquisition of funds and delineate the cost of education. This study develops a typology of community college funding formulas placing 48 states in three categories and five subcategories.

At the Community College Futures Assembly, 3 critical discussion groups, each organized by an area of focus, conceptualized “New Rules” guiding the operation of community colleges. Utilizing 55 “New Rules for Business” provided by the keynote speaker Mark N. Vamos, each group identified 2–3 New Rules relevant to community college leadership in the future, suggested how they may be resolved, and then suggested areas for future research. Assembly participants were provided the opportunity to electronically vote as to which New Rules they felt were relevant to community college leaders in the coming years. Results were simultaneously displayed, allowing conference attendees to receive real-time feedback of the participant perceptions.

Background Heart failure (HF) ambulatory disease management programs appear to offer the greatest benefit to HF patients at highest risk, defined as having New York Heart Association (NYHA) functional Class III or IV symptoms. The Latitude Patient Management System is the first HF management tool to use wireless telemetry present in a cardiac resynchronization therapy defibrillator (CRT-D) device that is linked to remotely collect blood pressure and weight measures, permitting a single transmission reporting device data. Potential advantages of this system include ease of data transmissions, correlation among measures of HF status, arrhythmic events, and device performance. However, the use and ultimate utility of these combined features for patient management are untested. Methods and Results The Remote Active Monitoring in Patients with Heart Failure (RAPID-RF) study is a multicenter registry that will enroll up to 1000 patients on the Latitude Patient Management System from approximately 100 centers. The primary objective is to examine physician responses to Latitude Active Monitoring data alerts by assessing alert-related medical interventions. Minimum follow-up will be 3 months after implant with a maximum follow-up time of 24 months after implant. Conclusions The RAPID-RF study will provide important preliminary data on how remotely collected HF and arrhythmic surveillance data alter the management of HF patients with CRT-D devices.

Most transgenic corn seed is now treated with systemic neonicotinoid insecticides. To address potential direct nontarget effects of these combined technologies, 16 Carabidae species from 10 genera (Agonum, Amara, Anisodactylus, Bembidion, Chlaenius, Harpalus, Patrobus, Poecilus, Pterostichus, and Scarites) field-collected from corn were directly exposed to Bacillus thuringiensis (Bt) Cry toxin-laden pollens and seed treatments in feeding and defined-dose bioassays. All adults readily fed on field or sweet corn pollens that expressed coleopteran-specific Cry3Bb1 or lepidopteran-targeting Cry1Ab/c, and no significant toxicity was observed. Adult survivorship ranged from 47 d for the predator Pterostichus melanarius (Illiger) to a year for the more omnivorous Scarites quadriceps Chaudoir, feeding solely on pollen containing 30–90 μg Cry3Bb1/g and water. In contrast, commercial doses of neonicotinoid seed treatments (imidacloprid, thiamethoxam, or clothianidin) elicited nearly complete mortality for ...

The relationship between 12-month CD4(+) cell count response and clinical outcome (AIDS-defining event or death) in a subset of 228 patients with a human immunodeficiency virus load >400 copies/mL despite receiving combination antiretroviral therapy as part of a larger randomized trial was defined by use of Cox models. The 12-month CD4(+) cell count responses were divided into 5 categories, ranging from decrease or no change (29% of patients) to a > or =100-cell/mm(3) increase (27% of patients). There was a lower risk of clinical progression for each incremental increase in CD4(+) cell count response. A 25-cell/mm(3) increase in CD4(+) cell count was associated with a 21% reduction in the risk of an AIDS-defining event or death (P

I would first like to thank Eboni [Zamani-Gallaher] and the CSCC [Council for the Study of Community Colleges] leadership for affording me this opportunity to be with you today, and at this time. I...

Cysteine proteinases predominate in the midgut fluid (MF) and oral secretion (OS) of adult western corn rootworm (WCR) based on their mild acidic pH optima (pH 6.0), enhanced activities after treatment with thiol reducing agents, and inhibition by selective cysteine proteinase inhibitors (PIs). Four cysteine PIs including E-64, calpeptin, calpain inhibitor II, and leupeptin (also a serine PI) strongly inhibited azocaseinolytic activity in a dose-dependent manner in both the MF and OS. The most significant effect on adult female WCR of cysteine PI consumption with corn pollen was the reduction in fecundity, but female survival was not apparently affected. Mean fresh weights for all PI-fed females were also lower than control groups. All PI-fed groups [E-64, calpain inhibitor I (Cal I) and leupeptin] had a significantly lower daily egg production than respective corn pollen-fed controls. E-64 was more potent than leupeptin and Cal I on inhibiting fecundity, which correlates with their relative anti-proteinase potency in vitro. E-64, Cal I, and leupeptin at 1.5-2 nmol/beetle/day reduced fecundity down to 25-45% of control values. Reduced egg production by PI-fed beetles results from a combination of the direct inhibition of protein digestion and a post-ingestive negative feedback mechanism, which reduces food intake. The supplement of ten essential amino acids into the E-64-treated pollen enhanced up to 3.7-fold the number of eggs laid compared to the E-64-fed group without these amino acids, suggesting that egg production is dependent on the supply of essential amino acids from corn pollen proteolysis.

Low-molecular-weight peptidyl proteinase inhibitors (PIs) including leupeptin, calpain inhibitor I, and calpeptin were found to be potent antifeedants for adult western corn rootworm (WCR) against the phagostimulation of cucurbitacin B (Cuc B) or a corn pollen extract (CPE). Leupeptin was the strongest (ED50 = 0.36 and 0.55 nmol/disk for Cuc B and CPE, respectively) among PIs tested with an antifeedant potency much stronger than the steroid progesterone (ED50 = 2.29 and 5.05 nmol/disk for Cuc B and CPE, respectively), but slightly less than the reference alkaloid, strychnine (ED50 = 0.17 and 0.37 nmol/disk for Cuc B and CPE, respectively). All active PIs contain a di- or tripeptidyl aldehyde moiety, indicating that PIs exert their antifeedant effects by covalent interaction with putative sulfhydryl (SH) groups on taste receptors as do these PIs with cysteine proteinases. However, opposite inhibition potency against Cuc B versus CPE by two thiol-group reducing agents, DTT and L-cysteine, and the results with other cysteine-modifying reagents obscure the net functional role of SH groups at WCR taste chemoreceptors. Surprisingly, the model phagostimulant for diabroticites, Cuc B, was more easily counteracted by these feeding deterrents than the stimulants present in CPE. Three-dimensional structure–antifeedant relationships for the PIs suggest that a novel taste chemoreception mechanism exists for these peptidyl aldehydes or that they fit partially into a strychnine binding pocket on protein chemoreceptors. Favorable economic benefit may be achieved if PIs are discovered to be useful in adult WCR control, since both pre- and postingestive sites would be targeted.

Honey bees are sensitive to widespread co-formulants used in agrochemicals, and evaluation of the role of these 'inerts or inactives' in pollinator decline is only in its formative stages. Lack of disclosure of formulation ingredients in major products and lack of adequate methods for their analysis constrain the assessment of total chemical load and agrochemical exposures on bees. Most studies to document pesticide effects on honey bees are performed without the formulation or other relevant spray adjuvant components used to environmentally apply the toxicant. Formulations are generally more toxic than active ingredients, particularly fungicides, by up to 26,000-fold based on published literature. Some 'inactive' candidates for future risk assessment for pollinators include the organosilicone surfactants and the co-solvent N-methyl-2-pyrrolidone.

Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental impacts of agrochemicals on non-target species such as bees. Why most formulations are more toxic to bees than respective active ingredients and how pesticides interact to cause pollinator decline cannot be answered without understanding the prevailing environmental chemical background to which bees are exposed. Modern pesticide formulations and seed treatments, particularly when multiple active ingredients are blended, require proprietary adjuvants and inert ingredients to achieve high efficacy for targeted pests. Although we have found over 130 different pesticides and metabolites in beehive samples, no individual pesticide or amount correlates with recent bee declines. Recently we have shown that honey bees are sensitive to organosilicone surfactants, nonylphenol polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co-formulants used in agrochemicals and frequent pollutants within the beehive. Effects include learning impairment for adult bees and chronic toxicity in larval feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are used and released into US environments. These synthetic organic chemicals are generally recognized as safe, have no mandated tolerances, and residues remain largely unmonitored. In contrast to finding about 70% of the pesticide active ingredients searched for in our pesticide analysis of beehive samples, we have found 100% of the other formulation ingredients targeted for analysis. These ‘inerts’ overwhelm the chemical burden from active pesticide, drug and personal care ingredients with which they are formulated. Honey bees serve as an optimal terrestrial bioindicator to determine if ‘the formulation and not just the dose makes the poison’.

To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF).The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis.A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820).We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection.

Consumption of pollens from several host plants was quantified for adult western corn rootworm, Diabrotica virgifera virgifera, with significantly more sweet corn and winter squash pollen consumed than that of common sunflower and Canada goldenrod. Sequential solvent extraction and chromatographic fractionation of host pollens, guided by a feeding bioassay of respective fractions, isolated dominant phagostimulatory activity in pools of free amino acids. Amino acid profiles were determined by TLC and HPLC analysis. For sweet corn pollen, proline was predominant, accounting for 70% of a total 95.3 μmol free amino acid/g pollen; serine, alanine, γ-aminobutyric acid (GABA), and asparagine occurred in decreasing order of concentration. In squash pollen, β-alanine predominated (30% of 111 μmol amino acid/g pollen), followed by asparagine, alanine, proline, and GABA. Histidine (42% of 83.8 μmol amino acid/g pollen), proline, aspartic acid, asparagine, and alanine were dominant for sunflower pollen; and for goldenrod, proline (51% of 50.6 μmol amino acid/g pollen), trans-hydroxyproline, serine, histidine, and alanine predominated. The five dominant amino acids from each pollen accounted for 80–90% of total amino acid content. Simple mixtures of some dominant amino acids, approximating levels found in sweet corn and squash pollen, gave phagostimulation similar to that of the crude extracts.

The phagostimulatory response of some diabroticite cucumber beetles toward triterpene cucurbitacins is used as a model in support of an alternative hypothesis explaining the evolution of pharmacophagous feeding behavior in insects. Whereas the use of noxious compounds from nonhost sources for purposes other than nutrition or host-plant recognition (pharmacophagy) has historically been explained in terms of the ancestral host hypothesis, we suggest that the less than perfect specificity of the binding properties of some peripheral receptors provides an opportunity for novel compounds sharing the configuration and polarity of target molecules to elicit a feeding response by coincidence rather than adaptive design.

The fourth edition of Fifty state systems of community colleges is the latest in a series of books coauthored by state directors. The book provides a collection of essays relating to the community ...

Sensitivities to β-hydrastine, strychnine and picrotoxinin were compared between two populations of western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), differing in their susceptibility to cyclodiene insecticides. The antifeedants are antagonists of γ-aminobutyric acid (GABA) neuroreceptors that may mediate gustation and, in the case of picrotoxinin, interact directly with the target site for cyclodiene insecticides. In combination with cucurbitacin B, a specific Diabroticite phagostimulant, cyclodiene-resistant beetles were two- to four-fold less sensitive to hydrastine and strychnine. The discrimination threshold for picrotoxinin was higher for resistant beetles; however, overall dose–response profiles were similar. Beetles were more sensitive to hydrastine and strychnine in combination with L-alanine, a general phagostimulant of less potency than cucurbitacin B. Dose–response slopes for the alkaloid-alanine combinations were double those of respective cucurbitacin B slopes, which indicates that phagostimulatory input from l-alanine was more negatively affected by the alkaloidal antifeedants than the respective cucurbitacin B treatments. Picrotoxinin sensitivity was similar in mixtures with either phagostimulant. Comparison of chemosensillum responses to strychnine was inconclusive. Results are discussed in context of GABA receptor pharmacology.

A strong correlation is shown between taste cell inputs and phagostimulatory outputs with predominant dietary pollen amino acids for western corn rootworm, Diabrotica virgifera virgifera. Behavioral and electrophysiological dose-response profiles in adult beetles are presented for five major free amino acids in host pollens. Differential responses were found with strongest phagostimulation and sensory response elicited by L-alanine and L-serine, followed in order by L-proline and beta-alanine. gamma-Aminobutyric acid gave the weakest and most sporadic response. ED(50) values for phagostimulation and chemosensory input were 28.3nmol/disk and 13mM, respectively, for L-alanine and 17nmol/disk and 11mM, respectively, for serine. Threshold values for the responses were approximately 1-2mM. These behavioral and chemosensory dose-response ranges correspond closely to levels of free amino acids present in host plant pollens. Use of these response values in development of a pollen chemosensory code for western corn rootworm feeding is discussed.

The effects of 52 amino acids and derivatives on feeding responses of adult western corn rootworm Diabrotica virgifera virgifera (WCR) were investigated. L-Alanine was the most phagostimulatory amino acid, followed by L-serine, and β-alanine. All three amino acids showed a dose–response pattern but at the highest dose (500 nmol/disk) feeding by WCR decreased. In structure–activity relationship studies, four structural features for stimulating WCR feeding were found. First, terminal carboxyl and amino acid groups must be intact since all structural modifications in these groups led to a considerable decrease in feeding. Second, a hydrophobic region sterically limited to a two-saturated-carbon insert between the amino and carboxyl groups is associated with stimulatory effects at the L-alanine taste receptor. Third, L-alanine and L-serine are much more potent stimulants than the D enantiomers of these amino acids. Fourth, the hydrogen domain on the α-carbon of L-alanine is sterically constrained. A β-hydroxyl group on the amino acid side chain, such as in L-serine, does not reduce stimulatory taste, which indicates the presence of another binding domain. Therefore, L-alanine and L-serine either have separate binding sites on the taste cells of WCR or an un-ionized, polar grouping extending from the hydrophobic domain of the L-alanine binding site is permitted. The three most phagostimulatory amino acids (L-alanine, L-serine, and β-alanine) are nonessential amino acids, suggesting that amino acid sensitivity in WCR may be tuned to quantitatively relevant signals rather than just nutritionally important amino acids in a food.

Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L.) health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax - fluvalinate, coumaphos, chlorothalonil, and chloropyrifos - tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common ‘inert’ ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

Structure–dose–feeding deterrency relationships were compared between the Colorado potato beetle, Leptinotarsa decemlineata (Say), and the western corn rootworm, Diabrotica virgifera virgifera LeConte, using 15 alkaloids, terpenoids, and phenolic derivatives. The former species, a specialist herbivore on selected alkaloid-rich Solanaceae species, was on average 100-times less sensitive to the antifeedant effects of alkaloids, but more similarly sensitive to the terpenoids and phenolics than the latter species, a generalist flower herbivore predominantly on Graminae, Cucurbitaceae, and Compositae species. Antifeedant ED50 values for the potato beetle and corn rootworm, each from closely related subfamilies of Chrysomelidae, ranged over four orders of dose magnitude among the 15 compounds with major species differences in stereosensitivity to β-hydrastines and analog sensitivity with the silphinenes. Extremes in sensitivity ranged from silphinene, a rare tricyclic sesquiterpene that is 53 times more active on the potato beetle to aconitine, which is 430 times more antifeedant to the corn rootworm. Among silphinene and its two hydrolysis derivatives, there was not a strong correlation between antifeedant potency and injected toxicity for the two beetle species, but there was correlation between behavioral activity and galeal taste cell electrophysiological threshold and frequency responses. That all of the established GABA- and glycinergic compounds tested were antifeedant for both species suggests a shared molecular mechanism for antifeedant taste chemoreception in these divergent Chrysomelidae species. Moreover, the wide differences in antifeedant sensitivities among these and other chrysomelids to a suite of ligand-gated ion channel antagonists implicate a common protein neuroreceptor type with extraordinary heterogeneity in beetle taste.

The phagostimulatory sensitivity of diabroticite (Coleoptera, Chrysomelidae, Galerucinae) species to cucurbitacins is not correlated with Cucurbitaceae specialization, indicating that other factors, including the absence of feeding deterrents, may influence host–plant affinities among these beetles. Quinoline, indole, and isoquinoline alkaloids and sesquiterpene lactones believed to antagonize γ-aminobutyric acid/glycine Cl− ionophores mediating chemoreception were tested on squash blossom disks for antifeedant activity to four diabroticite species with different host plant specializations. Most alkaloids were antifeedant below 30 nmol/disk. Antifeedant concentrations of sesquiterpene lactones were higher than alkaloids for all species. Oligophagous Diabrotica virgifera virgifera was more sensitive to quinoline alkaloids than polyphagous D. undecimpuntata howardi. Diabrotica virgifera virgifera was also more sensitive to the indole alkaloids strychnine, brucine, eburnamonine, and vincamine than D. u. howardi. The closely related D. barberi had sensitivities similar to those of D. v. virgifera but the more distantly related Acalymma vittatum was less sensitive to the antifeedants than D. v. virgifera The isoquinoline alkaloid hydrastine was uniformly antifeedant to all diabroticites. All the GABA/glycine neurotoxicams tested against diabroticites were feeding deterrents and suggest that beetles share a common antifeedant mechanism.

Ablation of maxillary appendages on western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera : Chrysomelidae), were used to determine which mouthparts were involved in discrimination between the phagostimulant, cucurbitacin B, and the phagodeterrent, strychnine. Strychnine deterred feeding in unablated beetles when its concentration on disks was equal to or higher than cucurbitacin B. Unilateral or bilateral lacinea ablation did not affect discrimination between cucurbitacin B and strychnine. Galeal ablations abolished strychnine deterrence at equimolar concentrations of both compounds but not at higher strychnine concentrations, whereas maxillary palp ablation had no effect. However, bilateral ablation of both galea and maxillary palps resulted in a loss of deterrence at all strychnine concentrations. These results indicated strychnine sensitive chemoreceptors were primarily located on the galeae and maxillary palps. However, beetles without galeae and palps still feed on disks suggesting that cucurbitacin B sensitive chemoreceptors were located on other mouthparts and contributed to cucurbitacin B phagostimulation.

Patients (Pts) with chronic kidney disease (CKD) and atrial fibrillation have a greater risk of stroke and death than those with normal renal function and are at higher risk for bleeding with oral anticoagulants (OAC). We analyzed the efficacy of left atrial appendage closure (LAAC) with WATCHMAN

Nonylphenol and octylphenol ethoxylates (NP(EO)n and OP(EO)n) are major toxicants in agrochemicals used around beehives. Here we developed a LC-MS method for analysis of NP(EO)3-13 and OP(EO)3-13 oligomers in bee hive matrices. Less than 2 g of honey, pollen or wax were extracted using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach. Recoveries for each oligomer in all matrices are between 75% and 111% at three spiked concentrations. The method proved to be rapid, precise and sensitive. Five honey, 10 pollen and 12 wax samples were collected and analysed. NP(EO)n was detected in every sample with concentrations ranging from 26 ppb to 10,239 ppb. Much higher NP(EO)n residues levels were found in wax followed by pollen than in honey. OP(EO)n concentrations on average were more than 10 times lower in pollen and wax. This method demonstrates a probable wide occurrence of alkylphenol ethoxylates in USA beehives.

Taste chemoreception is essential for animals to select suitable foods. Gustatory sensilla concentrated on mouthparts, other external appendages, or the food canal are responsible for transduction of chemical stimuli into nerve signals that trigger behavioral acceptance or rejection of a potential nutrient source. Insects have primary taste neurons containing both a dendrite and a direct axonal connection to the central nervous system, whereas receptor cells and afferent neurons are separated by a synapse in vertebrates. Taste receptor proteins have not been successfully purified or cloned from any animal to date. Our recent work with western corn rootworm beetles, Diabrotica virgifera virgifera LeConte, implicates a γ-aminobutyric acid (GABA)/glycine receptor in the perception of phago-stimulants and -deterrents. GABA stimulates feeding in herbivorous members of four orders of insects. The merits of this ligand-gated receptor model for chemoreception of ‘sweet’, ‘bitter’ and other taste classes will be contrasted with those proposed from vertebrate studies. Possibly one receptor gene family allows for insect perception of both food cues and potentially toxic non-host or environmental chemicals prior to their action at critical internal sites. Studies of taste receptors offer advantages over other insect neuroreceptors by their external location which simplifies ligand pharmacodynamics and allows coupled use of behavioral and electrophysiological methods to directly link receptor pharmacology with function.

Following in vivo injection of [1-14C]-sodium acetate, triacylglycerols of the potato aphid, Macrosiphum euphorbiae (Thomas), were extracted and derivatized to p-bromophenacyl fatty acid esters for two-dimensional TLC and GLC-MSD (mass selective detector) analysis. Radiolabeled sorbic (E, E-2,4-hexadienoic) acid ester was detected, demonstrating that this short chain fatty acid unique to aphids is biosynthesized via an acetogenic pathway. Crotonic (E-2-butenoic) or hexenoic acids were not detected in labeled or unlabeled potato aphid samples or unlabeled samples from the oleander aphid, Aphis nerii Fonscolombe. Crotonic or hexenoic acids might have been expected if an incomplete cycling by fatty acid synthetase or a novel desaturase acting on the prevalent hexanoate, respectively, were responsible for sorbic acid synthesis in aphids. A peroxisomal β-oxidation route to sorbic acid from longer chain fatty acids was not indicated since injections of clofibrate, a peroxisomal proliferator, with or without C18 polyunsaturated lipids gave no substantial increase in C6 lipids. Also, some characteristic enzyme activities of peroxisomal β-oxidation were not found in an ultracentrifugal “peroxisomal” fraction from the potato aphid. Although the individual biochemical steps from acetate to sorbate in aphids remain unclear, an unusual acetate-malonate pathway is indicated. Clarification of the biosynthetic steps to sorbic acid should identify at least one novel enzyme for animals. © 1994 Wiley-Liss, Inc.

Studies were undertaken to determine the role of symbionts and UV exposure in biosynthesis of the aphid-specific polyketides, sorbic acid and quinone pigments. Injection of adult potato aphids, Macrosiphum euphorbiae (Thomas), with the antibiotic rifampicin did not alter the level of sorbic or myristic acid in triglycerides of resultant progeny; pigmentation was also unaffected. However, antibiotic injection did produce marked physiological effects; progeny from injected aphids were smaller, slower to mature, and not fecund. Light microscopy confirmed that only 8% of rifampicin-treated aphids contained mycetocytes; thus, symbiont involvement in the production of this unusual UV-quenching short chain fatty acid is not supported. Following multigenerational exposure to long wavelength UV light, no substantial changes in sorbic acid content were detected in the potato aphid or the oleander aphid, Aphis nerii Fonscolombe. Pigments from UV-exposed oleander aphids had a peak absorbance at 390 nm, 70 nm lower than unexposed aphids. This suggests a photo-protective role for the pigments of the sunlight-inhabiting A. nerii; by contrast, no changes were observed in pigments of M. euphorbiae which usually feeds in the shade. Injection of adult potato aphids with sodium [1-14C]-acetate rapidly labeled both sorbic acid and pigments, particularly among the latter a yellow pigment which co-chromatographed with the dominant C15 yellow pigment of the oleander aphid. These data support the hypothesis that aphid C30 pigments are built up by coupling of “monomeric type” C15 pigments. Although aphid and not symbiont enzymes appear to synthesize these acetogenins, a possible biosynthetic link between sorbic acid and aphid pigments requires further clarification. © 1994 Wiley-Liss, Inc.

POWER KNEE is the world’s first intelligent motor powered prosthetic knee. The knee replaces lost muscle functions and is designed to increase gait symmetry and to reduce unwanted load in level ground walking, stair and ramp descent/ascent, sitting down and standing up. During the first part of swing phase, in general, the knee joint flexes, lifting the foot off the ground. This is an important part of the swing phase as insufficient ground clearance at initial swing has a rippling effect throughout the whole phase and can cause toe stubbing, insecurity of the user, and as a result some types of gait deviations. User of a passive prosthesis knee joint uses his hip to force the foot off the ground whereas a powered knee joint can actively flex the knee at the right moment, ensuring enough ground clearance throughout the swing phase. Every prosthetic knee joint has some internal resistance, which needs to be overcome in order to transfer from knee flexion to extension in swing. In order to overcome this internal resistance, users of passive knee joints use excessive hip power to force the joint into extension. This can cause gait deviations and insecurity for the user as the center of mass is shifted back. An intelligent motor powered knee joint has the ability to remove this unwanted action by actively extending the knee at the right moment. Another benefit of a motor powered prosthesis is that the motor can be actively locked in any flexed position without the risk of the joint buckling. This means that the joint does not have to be fully extended at heel strike and the extension at terminal swing can be fine tuned to leave the joint in approximately 5 deg flexion, imitating the position of a healthy knee. While the motor is blocked at heel strike, avoiding buckling, a mechanical spring controls a stance flexion angle. The stance flexion works as a shock absorption and ensures more symmetry during walking. In addition to controlling the speed and amount of flexion and extension of the knee joint in every gait cycle, a powered knee prosthesis provides the user with enough lifting power to ascend stairs step over step and stand up from a chair with equal weight on the sound side and the prosthesis side. This important feature reduces the unsymmetrical load put on the sound side, arms, and shoulders in those activities.

The economic state of affairs facing states of the twenty-first century posed substantial threat to the future availability of public funds for postsecondary education. The American Recovery and Reinvestment Act (Public Law 111–5 2009) provided temporary relief to state budgets through the State Fiscal Stabilization Fund to ensure that appropriate funding continues for education and government services.