Sample records for intermeal interval imi

  1. CCK-58 Elicits Both Satiety and Satiation in Rats while CCK-8 Elicits Only Satiation

    PubMed Central

    Overduin, Joost; Gibbs, James; Cummings, David E.; Reeve, Joseph R.

    2014-01-01

    Reduction of food intake by exogenous cholecystokinin (CCK) has been demonstrated primarily for its short molecular form, CCK-8. Mounting evidence, however, implicates CCK-58 as a major physiologically active CCK form, with different neural and exocrine response profiles than CCK-8. In three studies, we compared meal-pattern effects of intraperitoneal injections CCK-8 vs. CCK-58 in undeprived male Sprague-Dawley rats consuming sweetened condensed milk. In study one, rats (N=10) received CCK-8, CCK-58 (0.45, 0.9, 1.8 and 3.6 nmole/kg) or vehicle before a 4-hour test-food presentation. At most doses, both CCK-8 and CCK-58 reduced meal size relative to vehicle. Meal-size reduction prompted a compensatory shortening of the intermeal interval (IMI) after CCK-8, but not after CCK-58, which uniquely increased the satiety ratio (IMI/size of the preceding meal). In the second study, lick patterns were monitored after administration of 0.9nmole/kg CCK-58, CCK-8 or vehicle. Lick cluster size, lick efficiency and interlick-interval distribution remained unaltered compared to vehicle, implying natural satiation, rather than illness, following both CCK forms. In study 3, threshold satiating doses of the two CCK forms were given at 5 and 30 minutes after meal termination, respectively. CCK 58, but not CCK-8 increased the intermeal interval and satiety ratio compared to vehicle. In conclusion, while CCK 58 and CCK-8 both stimulate satiation, thereby reducing meal size, CCK-58 consistently exerts a satiety effect, prolonging IMI. Given the physiological prominence of CCK-58, these results suggest that CCK’s role in food intake regulation may require reexamination. PMID:24468546

  2. "What time is my next meal?" delay-discounting individuals choose smaller portions under conditions of uncertainty.

    PubMed

    Zimmerman, Annie R; Ferriday, Danielle; Davies, Sarah R; Martin, Ashley A; Rogers, Peter J; Mason, Alice; Brunstrom, Jeffrey M

    2017-09-01

    'Dietary' delay discounting is typically framed as a trade-off between immediate rewards and long-term health concerns. Our contention is that prospective thinking also occurs over shorter periods, and is engaged to select portion sizes based on the interval between meals (inter-meal interval; IMI). We sought to assess the extent to which the length of an IMI influences portion-size selection. We predicted that delay discounters would show 'IMI insensitivity' (relative lack of concern about hunger or fullness between meals). In particular, we were interested in participants' sensitivity to an uncertain IMI. We hypothesized that when meal times were uncertain, delay discounters would be less responsive and select smaller portion sizes. Participants (N = 90) selected portion sizes for lunch. In different trials, they were told to expect dinner at 5pm, 9pm, and either 5pm or 9pm (uncertain IMI). Individual differences in future-orientation were measured using a monetary delay-discounting task. Participants chose larger portions when the IMI was longer (p < 0.001). When the IMI was uncertain, delay-discounting participants chose smaller portions than the average portion chosen in the certain IMIs (p < 0.05). Furthermore, monetary discounting mediated a relationship between BMI and smaller portion selection in uncertainty (p < 0.05). This is the first study to report an association between delay discounting and IMI insensitivity. We reason that delay discounters selected smaller portions because they were less sensitive to the uncertain IMI, and overlooked concerns about potential future hunger. These findings are important because they illustrate that differences in discounting are expressed in short-term portion-size decisions and suggest that IMI insensitivity increases when meal timings are uncertain. Further research is needed to confirm whether these findings generalise to other populations. Copyright © 2017. Published by Elsevier Ltd.

  3. Obese and overweight individuals are less sensitive to information about meal times in portion size judgements.

    PubMed

    Zimmerman, A R; Mason, A; Rogers, P J; Brunstrom, J M

    2017-11-16

    Obesity is related to a tendency to discount the future. Information regarding inter-meal interval (IMI) allows meal planning. We sought to assess how obese, overweight, and lean people select portion sizes based on the length of an IMI. We hypothesised that individuals with a high BMI would discount information about the IMI. In addition, we investigated how reduced sensitivity to IMIs relates to monetary temporal discounting. Participants (lean, n=35; overweight, n=31; obese, n=22), selected lunchtime portion sizes in response to information about the timings of their next meal. In seven trials, the time of the IMI was systematically manipulated, ranging from 'right now' to '8 h'. Participants then completed a monetary temporal discounting task. BMI was included as a continuous measure. For each participant, we conducted a linear regression of portion size on IMI to yield a gradient that reflected reduced sensitivity to future meal timings. As expected, participants selected larger portion sizes in response to a long IMI. Consistent with our hypothesis, individuals with a high BMI discounted information about the IMI (β=-3.49, P=0.015; confidence interval (CI) 6.29 to -0.70). Monetary discounting also negatively predicted BMI (β=-8.1, P=0.003; CI=-13.43 to -2.77), but did not correlate with IMI sensitivity (P>0.05). These results are the first to demonstrate that temporal discounting operates in planning from one meal to the next, and is more prevalent in obese and overweight, relative to lean individuals. Participants with a high BMI discounted concerns about potential future fullness and hunger in the IMI. Our observations might begin to explain associations between obesity and irregular meal timings or help to form the basis for a targeted intervention that promotes future thinking in meal planning.International Journal of Obesity accepted article preview online, 16 November 2017. doi:10.1038/ijo.2017.275.

  4. Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin releasing peptides

    PubMed Central

    Washington, Martha C.; Mhalhal, Thaer R.; Berger, Tanisha Johnson-Rouse Jose; Heath, John; Seeley, Randy; Sayegh, Ayman I.

    2016-01-01

    Background Roux-en-Y gastric bypass (RYGB) is the most effective method for the treatment of obesity and metabolic disease Roux-en-Y gastric bypass (RYGB) may reduce body weight by altering the feeding responses evoked by the short term satiety peptides. Materials and Methods Here, we measured meal size (MS, chow), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS; food consumed per a unit of time) by the small and the large forms of gastrin releasing peptide (GRP) in rats, GRP-10 and GRP-29 (0, 0.1, 0.5 nmol/kg) infused in the celiac artery (CA, supplies stomach and upper duodenum) and the cranial mesenteric artery (CMA, supplies small and large intestine) in a RYGB rat model. Results GRP-10 reduced MS, prolonged the IMI and increased the SR only in the RYGB group, whereas GRP-29 evoked these responses by both routes and in both groups. Conclusion The RYGB procedure augments the feeding responses evoked by exogenous GRP, possibly by decreasing total food intake, increasing latency to the first meal, decreasing number of meals or altering the sites of action regulating MS and IMI length by the two peptides. PMID:27884350

  5. Exogenous glucagon-like peptide-1 reduces body weight and cholecystokinin-8 enhances this reduction in diet-induced obese male rats.

    PubMed

    Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

    2017-10-01

    The sites of action regulating meal size (MS) and intermeal interval (IMI) length by glucagon like peptide-1 (7-36) (GLP-1 (7-36)) and cholecystokinin-8 (CCK-8) reside in the areas supplied by the two major branches of the abdominal aorta, celiac and cranial mesenteric arteries. We hypothesized that infusing GLP-1 near those sites reduces body weight (BW) and adding CCK-8 to this infusion enhances the reduction. Here, we measured BW in diet-induced obese (DIO) male rats maintained and tested on normal rat chow and infused with saline, GLP-1 (0.5nmol/kg) and GLP-1+CCK-8 (0.5nmol/kg each) in the aorta once daily for 21days. We found that GLP-1 and GLP-1+CCK-8 decrease BW relative to saline vehicle and GLP-1+CCK-8 reduced it more than GLP-1 alone. Reduction of BW by GLP-1 alone was accompanied by decreased 24-h food intake, first MS, duration of first meal and number of meals, and an increase in latency to first meal. Reduction of BW by the combination of the peptides was accompanied by decrease 24-h food intake, first MS, duration of first meal and number of meals, and increase in the IMI length, satiety ratio and latency to first meal. In conclusion, GLP-1 reduces BW and CCK-8 enhances this reduction if the peptides are given near their sites of action. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Comparison of transmission dynamics between Streptococcus uberis and Streptococcus agalactiae intramammary infections.

    PubMed

    Leelahapongsathon, Kansuda; Schukken, Ynte Hein; Pinyopummintr, Tanu; Suriyasathaporn, Witaya

    2016-02-01

    The objectives of study were to determine the transmission parameters (β), durations of infection, and basic reproductive numbers (R0) of both Streptococcus agalactiae and Streptococcus uberis as pathogens causing mastitis outbreaks in dairy herds. A 10-mo longitudinal study was performed using 2 smallholder dairy herds with mastitis outbreaks caused by Strep. agalactiae and Strep. uberis, respectively. Both herds had poor mastitis control management and did not change their milking management during the entire study period. Quarter milk samples were collected at monthly intervals from all lactating animals in each herd for bacteriological identification. The durations of infection for Strep. uberis intramammary infection (IMI) and Strep. agalactiae IMI were examined using Kaplan-Meier survival curves, and the Kaplan-Meier survival functions for Strep. uberis IMI and Strep. agalactiae IMI were compared using log rank survival-test. The spread of Strep. uberis and Strep. agalactiae through the population was determined by transmission parameter, β, the probability per unit of time that one infectious quarter will infect another quarter, assuming that all other quarters are susceptible. For the Strep. uberis outbreak herd (31 cows), 56 new infections and 28 quarters with spontaneous cure were observed. For the Strep. agalactiae outbreak herd (19 cows), 26 new infections and 9 quarters with spontaneous cure were observed. The duration of infection for Strep. agalactiae (mean=270.84 d) was significantly longer than the duration of infection for Strep. uberis (mean=187.88 d). The transmission parameters (β) estimated (including 95% confidence interval) for Strep. uberis IMI and Strep. agalactiae IMI were 0.0155 (0.0035-0.0693) and 0.0068 (0.0008-0.0606), respectively. The R0 (including 95% confidence interval) during the study were 2.91 (0.63-13.47) and 1.86 (0.21-16.61) for Strep. uberis IMI and Strep. agalactiae IMI, respectively. In conclusion, the transmission parameter and R0 values were not different between both pathogens; however, the duration of infection for Strep. agalactiae was longer than Strep. uberis. These suggest that Strep. uberis may have a different transmission dynamic compared with Strep. agalactiae. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Perineal swelling, intermenstrual cycle, and female sexual behavior in bonobos (Pan paniscus).

    PubMed

    Paoli, T; Palagi, E; Tacconi, G; Tarli, S Borgognini

    2006-04-01

    Many reports have claimed that the duration of the swelling cycle in female bonobos (Pan paniscus) is longer than that of chimpanzees, and that the bonobo maximum swelling phase is markedly prolonged. Field data on intermenstrual intervals (IMIs) in female bonobos are limited and restricted to interswelling intervals (ISIs), which are assumed to reflect the IMI, though a direct comparison between the duration of ISIs and IMIs is still lacking. Reports on bonobo sexual activity as a function of the swelling phase are often contradictory. Moreover, the function of female homosexual interactions (genito-genital (GG) rubbing) is still debated. This study examines the reliability of the ISI as an approximation of the IMI, and the attractivity of female sexual swellings for other individuals. An analysis of 51 ISI-IMI pairs showed that ISIs are a fair representation of the reproductive cycle. The cycle length was 35.6+/-1.1 SE days relying on the ISI, whereas it was 35.0+/-1.1 SE days considering the IMI. This result is similar to the cycle length reported for chimpanzees. Female homosexual interactions and copulatory rates were higher during maximum tumescence, suggesting that the sexual swelling may be attractive for both males and other females. Furthermore, the GG-rubbing was performed free of a hierarchical postural imposition, and was not correlated with affinitive interactions. We suggest that GG-rubbing, which is generally the most frequent female sexual interaction, is a tool for social assessments among females. Copyright (c) 2006 Wiley-Liss, Inc.

  8. Epidemiology of coagulase-negative staphylococci intramammary infection in dairy cattle and the effect of bacteriological culture misclassification.

    PubMed

    Dufour, S; Dohoo, I R; Barkema, H W; Descôteaux, L; Devries, T J; Reyher, K K; Roy, J-P; Scholl, D T

    2012-06-01

    Objectives of this study were to identify the manageable risk factors associated with the lactational incidence, elimination, and prevalence of coagulase-negative staphylococci (CNS) intramammary infections (IMI) while taking into account the difficulties inherent to their diagnosis. A second objective was to evaluate the effect of CNS IMI misclassification in mastitis research. A cohort of 90 Canadian dairy herds was followed throughout 2007 to 2008. In each herd, series of quarter milk samples were collected from a subsample of cows and bacteriological culture was performed to identify prevalent, incident, and eliminated CNS IMI. Practices used on farms were captured using direct observations and a validated questionnaire. The relationships between herd CNS IMI prevalence and herd incidence and elimination rates were explored using linear regression. Manageable risk factors associated with the prevalence, incidence, or elimination of CNS IMI were identified via Bayesian analyses using a latent class model approach, allowing adjustment of the estimates for the imperfect sensitivity and specificity of bacteriological culture. After adjustment for the diagnostic test limitations, a mean CNS IMI quarter prevalence of 42.7% [95% confidence interval (CI): 34.7, 50.1] and incidence and elimination rates of 0.29 new IMI/quarter-month (95% CI: 0.21, 0.37) and 0.79 eliminated IMI/quarter-month (95% CI: 0.66, 0.91), respectively, were observed. Considerable biases of the estimates were observed when CNS IMI misclassification was ignored. These biases were important for measures of association with risk factors, were almost always toward the null value, and led to both type I and type II errors. Coagulase-negative staphylococci IMI incidence appeared to be a stronger determinant of herd IMI prevalence than IMI elimination rate. The majority of herds followed were already using blanket dry cow treatment and postmilking teat disinfection. A holistic approach considering associations with all 3 outcomes was used to interpret associations between manageable risk factors and CNS IMI. Sand and wood-based product bedding showed desirable associations with CNS IMI compared with straw bedding. Quarters of cows that had access to pasture during the sampling period had lower odds of acquiring a new CNS IMI and of having a prevalent CNS IMI. Many practices showed an association with only one of the CNS outcomes and should, therefore, be considered with caution. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Abdominal adiposity is not a mediator of the protective effect of Mediterranean diet on colorectal cancer.

    PubMed

    Fasanelli, Francesca; Zugna, Daniela; Giraudo, Maria Teresa; Krogh, Vittorio; Grioni, Sara; Panico, Salvatore; Mattiello, Amalia; Masala, Giovanna; Caini, Saverio; Tumino, Rosario; Frasca, Graziella; Sciannameo, Veronica; Ricceri, Fulvio; Sacerdote, Carlotta

    2017-05-15

    Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e., waist-to-hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk. We then estimated the natural indirect effect (NIE, mediated by WHR) and the pure direct effect (PDE, unmediated) of IMI on CRC risk using mediation analyses, considering age, sex, education, physical activity, smoking and EPIC centre as confounders. Increased IMI was associated with significantly decreased odds of high WHR (odds ratio [OR] for an IMI of 6-11 vs. 0-1: 0.88, 95% confidence interval [CI]: 0.81-0.97). There was a positive relationship between WHR and CRC (hazard ratio [HR] for high vs. low WHR: 1.34, 95%CI: 1.09-1.66). The total effect of IMI was protective on CRC risk and was mainly explained by the PDE (HR for an IMI of 6-11 vs. 0-1: 0.51, 95%CI: 0.31-0.83), whereas the NIE was 1.00 (95%CI: 0.94-1.10). In this Mediterranean cohort, the protective effect of the MD on the development of CRC was not mediated by abdominal adiposity. Since this is the first study to investigate the mediating effect of abdominal obesity, other studies are needed to replicate this result. © 2017 UICC.

  10. The relationship between the INTERMED patient complexity instrument and Level of Care Utilisation System (LOCUS).

    PubMed

    Thurber, Steven; Wilson, Ann; Realmuto, George; Specker, Sheila

    2018-03-01

    To investigate the concurrent and criterion validity of two independently developed measurement instruments, INTERMED and LOCUS, designed to improve the treatment and clinical management of patients with complex symptom manifestations. Participants (N = 66) were selected from hospital records based on the complexity of presenting symptoms, with tripartite diagnoses across biological, psychiatric and addiction domains. Biopsychosocial information from hospital records were submitted to INTERMED and LOCUS grids. In addition, Global Assessment of Functioning (GAF) ratings were gathered for statistical analyses. The product moment correlation between INTERMED and LOCUS was 0.609 (p = .01). Inverse zero-order correlations for INTERMED and LOCUS total score and GAF were obtained. However, only the beta weight for LOCUS and GAF was significant. An exploratory principal components analysis further illuminated areas of convergence between the instruments. INTERMED and LOCUS demonstrated shared variance. INTERMED appeared more sensitive to complex medical conditions and severe physiological reactions, whereas LOCUS findings are more strongly related to psychiatric symptoms. Implications are discussed.

  11. Electron-induced chemistry in imidazole clusters embedded in helium nanodroplets

    NASA Astrophysics Data System (ADS)

    Kuhn, Martin; Raggl, Stefan; Martini, Paul; Gitzl, Norbert; Darian, Masoomeh Mahmoodi; Goulart, Marcelo; Postler, Johannes; Feketeová, Linda; Scheier, Paul

    2018-02-01

    Electron-induced chemistry in imidazole (IMI) clusters embedded in helium nanodroplets (with an average size of 2 × 105 He atoms) has been investigated with high-resolution time-of-flight mass spectrometry. The formation of both, negative and positive, ions was monitored as a function of the cluster size n. In both ion spectra a clear series of peaks with IMI cluster sizes up to at least 25 are observed. While the anions are formed by collisions of IMI n with He*-, the cations are formed through ionization of IMI n by He+ as the measured onset for the cation formation is observed at 24.6 eV (ionization energy of He). The most abundant series of anions are dehydrogenated anions IMI n-1(IMI-H)-, while other anion series are IMI clusters involving CN and C2H4 moieties. The formation of cations is dominated by the protonated cluster ions IMI n H+, while the intensity of parent cluster cations IMI n + is also observed preferentially for the small cluster size n. The observation of series of cluster cations [IMI n CH3]+ suggests either CH3+ cation to be solvated by n neutral IMI molecules, or the electron-induced chemistry has led to the formation of protonated methyl-imidazole solvated by ( n - 1) neutral IMI molecules.

  12. International Map Year: Results and Implications

    NASA Astrophysics Data System (ADS)

    Rystedt, Bengt; Ormeling, Ferjan; Buckley, Aileen; Coetzee, Serena; Voženilek, Vit; Fairbairn, David; Kagawa, Ayako

    2018-05-01

    IMY was a worldwide celebration of maps and their unique role in our world. Supported by the United Nations, IMY provides opportunities to demonstrate, follow, and get involved in the art, science, and technology of making and using maps and geographic information. International Map Year (IMY) started in Paris 2011 when the General Assembly of the International Cartographic Association (ICA) asked the ICA Executive Committee (EC) to follow up on the proposal given in a motion from the Swedish Cartographic Society. An IMY Working Group (WG) was constituted - it defined the IMY goals and the activities required to reach them, and it proposed a suitable time period for the IMY to the ICA EC. IMY commenced in August 2015 and ended in December 2016. The success of IMY was dependent on all member nations of the ICA participating in an effort to broaden the knowledge of cartography and geographic information in society in general, especially among citizens and school children. Member nations of the ICA were responsible for organizing IMY activities, such as a national Map Day, through national IMY committees tasked to engage national organizations and spearheading collaboration. The IMY WG set up an IMY web site with general information on IMY, guidelines for how to organize Map Days, suggestions relating to activities aimed at general map awareness, and more. The web site also provides access to the electronic book The World of Maps, which has been translated from English into five other languages.

  13. Association of standing and lying behavior patterns and incidence of intramammary infection in dairy cows milked with an automatic milking system.

    PubMed

    Devries, T J; Deming, J A; Rodenburg, J; Seguin, G; Leslie, K E; Barkema, H W

    2011-08-01

    The standing and lying behavior patterns of dairy cows, particularly the length of time cows spend standing after milking, have the potential to influence the incidence of intramammary infection (IMI). The objectives were to describe the standing and lying behavior patterns of cows milked with an automatic milking system (AMS) and to determine how these patterns relate to the incidence of IMI. One hundred and eleven lactating Holstein dairy cows were monitored over a 4-mo period. These cows were kept in a sand-bedded freestall barn with 2 pens, each with a free cow traffic AMS. Feed was delivered once daily, and pushed up 2 to 3 times daily. Quarter milk samples were collected for bacteriological culture from each cow once every 4 wk. A new IMI was defined as a positive culture sample following a negative culture. For 7 d before each of the last 3 milk samplings, standing and lying behavior, and times of milking and feed manipulation (feed delivery and push up) were recorded. Daily lying time and lying bout length were negatively related with milk yield (r=-0.23 and -0.20, respectively) and milking frequency (r=-0.32 and -0.20, respectively); milk yield was positively related to milking frequency (r=0.58). Feed manipulation near the time cows were milked (1h before 2h after) resulted in the longest post-milking standing times (mean=86 min; 95% confidence interval=78, 94 min), whereas feed manipulation occurring outside that time frame resulted in shorter post-milking standing times. Over the study period, 171 new IMI were detected. Of these new IMI detected, those caused by coagulase-negative staphylococci were the only ones associated with post-milking standing time; as post-milking standing time increased past 2.5h after milking, the odds of acquiring a new IMI tended to also increase. In summary, standing and lying behavior patterns of cows milked with an AMS were affected by both feed manipulation and their milking activity. Further, the post-milking standing time of cows milked with an AMS can be managed by providing fresh feed, as well as by pushing up feed, frequently throughout the day. Finally, cows that spend long periods of time (>2.5h) standing following milking may be at higher risk of acquiring a new CNS IMI. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. System-wide Benefits of Intermeal Fasting by Autophagy.

    PubMed

    Martinez-Lopez, Nuria; Tarabra, Elena; Toledo, Miriam; Garcia-Macia, Marina; Sahu, Srabani; Coletto, Luisa; Batista-Gonzalez, Ana; Barzilai, Nir; Pessin, Jeffrey E; Schwartz, Gary J; Kersten, Sander; Singh, Rajat

    2017-12-05

    Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin. ITAD feeding decreases adiposity and, unlike CR, enhances muscle mass. ITAD feeding drives energy expenditure, lowers lipid levels, suppresses gluconeogenesis, and prevents age/obesity-associated metabolic defects. Using liver-, adipose-, myogenic-, and proopiomelanocortin neuron-specific autophagy-null mice, we mapped the contribution of tissue-specific autophagy to system-wide benefits of ITAD feeding. Our studies suggest that consuming two meals a day without CR could prevent the metabolic syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. In vitro evaluation of five rapid antigen detection tests for group A beta-haemolytic streptococcal sore throat infections.

    PubMed

    Lasseter, Gemma M; McNulty, Cliodna A M; Richard Hobbs, F D; Mant, David; Little, Paul

    2009-12-01

    Using accurate and easy to use rapid antigen detection tests (RADTs) to identify group A beta-haemolytic Streptococci (GABHS) sore throat infections could reduce unnecessary antibiotic prescribing and antimicrobial resistance. Although there is no international consensus on the use of RADTs, these kits have been widely adopted in Finland, France and the USA. Yet in the UK, the Clinical Knowledge Summaries, that provide the main online guidance for GPs, discourage RADTs use, citing their poor sensitivity and inability to impact on prescribing decisions in acute sore throat infections. The purpose of this study was to evaluate the ease of use and in vitro accuracy (sensitivity and specificity) of the five most commonly used RADTs in Europe (OSOM Ultra, Quickvue Dipstick, Streptatest, Clearview Exact Strep A and IMI Test Pack). To ensure the RADTs were evaluated objectively, a standardized in vitro method using known concentrations of GABHS was used to remove the inherent biases associated with clinical studies. The IMI Test Pack was the easiest RADT to use overall. The ability to detect all positive GABHS (sensitivity) varied considerably between kits from 95% [95% confidence interval (CI): 88-98%], for the IMI Test Pack and OSOM, to 62% (95% CI: 51-72%) for Clearview, at the highest GABHS concentration. None of the RADTs gave any false-positive results with commensal flora-they were 100% specific. The IMI Test Pack is most suitable for use in primary care, as it had high sensitivity, high specificity and was easy to use.

  16. Voltage Dependence of a Neuromodulator-Activated Ionic Current.

    PubMed

    Gray, Michael; Golowasch, Jorge

    2016-01-01

    The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca(2+), but that, in conditions of low Ca(2+), calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca(2+)/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR.

  17. Voltage Dependence of a Neuromodulator-Activated Ionic Current123

    PubMed Central

    2016-01-01

    Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619

  18. Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease.

    PubMed

    Berent, S; Giordani, B; Foster, N; Minoshima, S; Lajiness-O'Neill, R; Koeppe, R; Kuhl, D E

    1999-01-01

    We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.

  19. Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

    PubMed Central

    Michaud, Laurent; Ludwig, Gundula; Berney, Sylvie; Rodrigues, Stéphanie; Niquille, Anne; Santschi, Valérie; Favre, Anne-Sophie; Lange, Anne-Catherine; Michels, Annemieke A.; Vrijens, Bernard; Bugnon, Olivier; Pilon, Nathalie; Pascual, Manuel; Venetz, Jean-Pierre; Stiefel, Friedrich; Schneider, Marie-Paule

    2016-01-01

    Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20). Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20). Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid patients who have complex social and psychological characteristics. PMID:28042353

  20. IMI's teaching design, feedback system and its localization

    NASA Astrophysics Data System (ADS)

    Wen, Tingting; Zhang, Xuexin

    2017-08-01

    In Britain, the Institute of the Motor Industry (IMI) sets the National Occupational Standards for all sectors of the automotive industry. The IMI certificate and associated training programs are well recognized for its high quality both in the United Kingdom (UK) and internationally. Using China's first groups studying IMI Level 3 certificate for teachers and Level 2 certificate for students as a sample, we analyzed the seven central aspects in IMI teaching, namely, assessment standard, environment, method, content, procedure, quality control and feedback. We then proposed strategies and guidelines for its localization in China, which would be particularly important for the establishment and expansion of IMI centers.

  1. Workplace measurements by the US Occupational Safety and Health Administration since 1979: descriptive analysis and potential uses for exposure assessment.

    PubMed

    Lavoue, J; Friesen, M C; Burstyn, I

    2013-01-01

    Inspectors from the US Occupational Safety and Health Administration (OSHA) have been collecting industrial hygiene samples since 1972 to verify compliance with Permissible Exposure Limits. Starting in 1979, these measurements were computerized into the Integrated Management Information System (IMIS). In 2010, a dataset of over 1 million personal sample results analysed at OSHA's central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only partially overlapping the IMIS database, was placed into public domain via the internet. We undertook this study to inform potential users about the relationship between this newly available OSHA data and IMIS and to offer insight about the opportunities and challenges associated with the use of OSHA measurement data for occupational exposure assessment. We conducted a literature review of previous uses of IMIS in occupational health research and performed a descriptive analysis of the data recently made available and compared them to the IMIS database for lead, the most frequently sampled agent. The literature review yielded 29 studies reporting use of IMIS data, but none using the CEHD data. Most studies focused on a single contaminant, with silica and lead being most frequently analysed. Sixteen studies addressed potential bias in IMIS, mostly by examining the association between exposure levels and ancillary information. Although no biases of appreciable magnitude were consistently reported across studies and agents, these assessments may have been obscured by selective under-reporting of non-detectable measurements. The CEHD data comprised 1 450 836 records from 1984 to 2009, not counting analytical blanks and erroneous records. Seventy eight agents with >1000 personal samples yielded 1 037 367 records. Unlike IMIS, which contain administrative information (company size, job description), ancillary information in the CEHD data is mostly analytical. When the IMIS and CEHD measurements of lead were merged, 23 033 (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%) records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD database. While IMIS-only records represent data analysed in other laboratories, CEHD-only records suggest partial reporting of sampling results by OSHA inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only datasets, respectively, suggesting differential under-reporting of non-detects in IMIS. IMIS and the CEHD datasets represent the biggest source of multi-industry exposure data in the USA and should be considered as a valuable source of information for occupational exposure assessment. The lack of empirical data on biases, adequate interpretation of non-detects in OSHA data, complicated by suspected differential under-reporting, remain the principal challenges to the valid estimation of average exposure conditions. We advocate additional comparisons between IMIS and CEHD data and discuss analytical strategies that may play a key role in meeting these challenges.

  2. [The informatics: a remarkable tool for teaching general internal medicine].

    PubMed

    Ombelli, Julien; Pasche, Olivier; Sohrmann, Marc; Monti, Matteo

    2015-05-13

    INTERMED training implies a three week course, integrated in the "primary care module" for medical students in the first master year at the school of medicine in Lausanne. INTERMED uses an innovative teaching method based on repetitive sequences of e-learning-based individual learning followed by collaborative learning activities in teams, named Team-based learning (TBL). The e-learning takes place in a web-based virtual learning environment using a series of interactive multimedia virtual patients. By using INTERMED students go through a complete medical encounter applying clinical reasoning and choosing the diagnostic and therapeutic approach. INTERMED offers an authentic experience in an engaging and safe environment where errors are allowed and without consequences.

  3. Workplace Measurements by the US Occupational Safety and Health Administration since 1979: Descriptive Analysis and Potential Uses for Exposure Assessment

    PubMed Central

    2013-01-01

    Background : Inspectors from the US Occupational Safety and Health Administration (OSHA) have been collecting industrial hygiene samples since 1972 to verify compliance with Permissible Exposure Limits. Starting in 1979, these measurements were computerized into the Integrated Management Information System (IMIS). In 2010, a dataset of over 1 million personal sample results analysed at OSHA’s central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only partially overlapping the IMIS database, was placed into public domain via the internet. We undertook this study to inform potential users about the relationship between this newly available OSHA data and IMIS and to offer insight about the opportunities and challenges associated with the use of OSHA measurement data for occupational exposure assessment. Methods : We conducted a literature review of previous uses of IMIS in occupational health research and performed a descriptive analysis of the data recently made available and compared them to the IMIS database for lead, the most frequently sampled agent. Results : The literature review yielded 29 studies reporting use of IMIS data, but none using the CEHD data. Most studies focused on a single contaminant, with silica and lead being most frequently analysed. Sixteen studies addressed potential bias in IMIS, mostly by examining the association between exposure levels and ancillary information. Although no biases of appreciable magnitude were consistently reported across studies and agents, these assessments may have been obscured by selective under-reporting of non-detectable measurements. The CEHD data comprised 1 450 836 records from 1984 to 2009, not counting analytical blanks and erroneous records. Seventy eight agents with >1000 personal samples yielded 1 037 367 records. Unlike IMIS, which contain administrative information (company size, job description), ancillary information in the CEHD data is mostly analytical. When the IMIS and CEHD measurements of lead were merged, 23 033 (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%) records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD database. While IMIS-only records represent data analysed in other laboratories, CEHD-only records suggest partial reporting of sampling results by OSHA inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only datasets, respectively, suggesting differential under-reporting of non-detects in IMIS. Conclusions : IMIS and the CEHD datasets represent the biggest source of multi-industry exposure data in the USA and should be considered as a valuable source of information for occupational exposure assessment. The lack of empirical data on biases, adequate interpretation of non-detects in OSHA data, complicated by suspected differential under-reporting, remain the principal challenges to the valid estimation of average exposure conditions. We advocate additional comparisons between IMIS and CEHD data and discuss analytical strategies that may play a key role in meeting these challenges. PMID:22952385

  4. Effect of disinfecting teats post-milking or pre- and post-milking on intramammary infection and somatic cell count.

    PubMed

    Williamson, J H; Lacy-Hulbert, S J

    2013-09-01

    To determine the effects of (a) post-milking teat disinfection compared with no disinfection and (b) pre- and post-milking teat disinfection compared with post-milking disinfection alone, on the incidence of new intramammary infection (IMI), somatic cell count (SCC) and teat skin abnormalities in dairy cows. In Experiment 1, dairy cows in five dairy herds were randomly allocated to a post-milking teat disinfection group (n=230), that was sprayed with an iodine-based disinfectant (TeatguardPlus) for a complete lactation, or to a non-disinfected group (n=239). In Experiment 2, cows were randomly allocated to post-milking teat disinfection (n=239) or both pre- and post-milking teat disinfection (n=235), using a chloramine-T-based disinfectant (Teatsweet) for both treatments, from calving to 118-127 days in milk. The incidence of new IMI was determined by aseptic sampling of all quarters at calving, during lactation, and at trial end or at drying-off, with clinical mastitis cases sampled on detection. SCC and teat skin abnormalities were measured at 2-monthly intervals during lactation. In both experiments, disinfectant was applied by spray application. Cows that received post-milking teat disinfection had a lower incidence of new IMI caused by Staphylococcus aureus, Streptococcus uberis, Corynebacterium spp and coagulase negative staphylococci, had lower bulk milk SCC during lactation, and had fewer teat skin abnormalities compared with the non-disinfected cows (p < 0.05). Pre-milking teat disinfection, in addition to post-milking teat disinfection, did not reduce the incidence of new IMI for any pathogens and did not reduce SCC (p> 0.05). Post-milking teat disinfection applied as a spray is a key component in mastitis control in New Zealand. There was no benefit from the addition of pre-milking disinfection. This study confirms previous findings of the effectiveness of post-milking teat disinfection in reducing the incidence of IMI caused by the common mastitis-causing pathogens in New Zealand, and presents the first results of a controlled study examining pre-milking teat spraying undertaken in New Zealand commercial dairy herds.

  5. Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis: MR Imaging of Airway Mucus Contrasts as a Tool for Diagnosis.

    PubMed

    Dournes, Gaël; Berger, Patrick; Refait, John; Macey, Julie; Bui, Stephanie; Delhaes, Laurence; Montaudon, Michel; Corneloup, Olivier; Chateil, Jean-François; Marthan, Roger; Fayon, Michaël; Laurent, François

    2017-10-01

    Purpose To assess the diagnostic accuracy of mucus contrast characterization by using magnetic resonance (MR) imaging to discriminate allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF). Materials and Methods The study was approved by the local Ethics Committee, and all patients or their parents gave written informed consent. One hundred ten consecutive patients with CF were screened between January 2014 and July 2015. All patients underwent a non-contrast material-enhanced MR protocol that included routine T1-weighted and T2-weighted sequences. The presence of mucus with both high T1 and low T2 signal intensities and the so-called inverted mucoid impaction signal (IMIS) sign was qualitatively and quantitatively assessed by two physicians who were blinded to all other data. The reference standard for a diagnosis of ABPA was the criteria of the Cystic Fibrosis Foundation Consensus Conference. ABPA status was followed up for 1 year. Reproducibility was assessed by using the κ test, correlation was assessed by using the Spearman coefficient, and diagnostic accuracy was assessed by calculating the sensitivity and specificity of IMIS. Results One hundred eight patients with CF were included (mean age, 20 years ± 11 [standard deviation]; range, 6-53 years): 18 patients with ABPA and 90 patients without ABPA. At the lobar level, inter- and intrareader reproducibility were very good (κ > 0.90). IMIS had 94% sensitivity (95% confidence interval [CI]: 73%, 99%) and 100% specificity (95% CI: 96%, 100%) for the diagnosis of ABPA. A complete resolution of IMIS was observed in patients with ABPA after 3 months of specific treatment that was significantly correlated with decrease in total immunoglobulin E level (ρ = 0.47; P = .04). Conclusion The IMIS sign was both specific and sensitive for the diagnosis of ABPA in CF. Allergic fungal inflammation appears to induce characteristic modifications of mucus contrasts that are assessable by using a noninvasive, contrast material-free, and radiation-free method. © RSNA, 2017 Online supplemental material is available for this article.

  6. Membrane permeability, a pivotal function involved in antibiotic resistance and virulence in Enterobacter aerogenes clinical isolates.

    PubMed

    Lavigne, J-P; Sotto, A; Nicolas-Chanoine, M-H; Bouziges, N; Bourg, G; Davin-Regli, A; Pagès, J-M

    2012-06-01

    Imipenem-susceptible E. aerogenes isolates exhibiting extended spectrum β-lactamases, target mutations and a basal efflux expression, were identified in five patients. After imipenem treatment, imipenem-intermediate susceptible (IMI-I) or resistant (IMI-R) isolates emerged in these patients. Alteration in porin synthesis and increase in efflux expression were observed in the IMI-I isolates whereas complete loss of the porins, LPS alteration and efflux overexpression were observed in the IMI-R isolates. Bacterial virulence of the strains was investigated by the Caenorhabditis elegans model. The IMI-R isolates were shown to be significantly less virulent than the IMI-susceptible or IMI-I isolates. The pleiotropic membrane alteration and its associated fitness burden exhibited by E. aerogenes isolates influence their antibiotic resistance and their virulence behaviour. These findings highlight the balance between the low permeability-related resistance and virulence and their relationships with the treatment of resistant pathogens. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  7. Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions.

    PubMed

    Lionakis, Michail S; Lewis, Russell E; Kontoyiannis, Dimitrios P

    2018-05-31

    Although the widespread use of mold-active agents (especially the new-generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including co-morbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.

  8. The effects analysis of two neonicotinoid insecticides on in vitro maturation of porcine oocytes using hanging drop monoculture method.

    PubMed

    Ishikawa, Sadamasa; Hiraga, Kou; Hiradate, Yuuki; Tanemura, Kentaro

    2015-06-01

    Acetamiprid (ACE) and imidacroprid (IMI) are known neonicotinoid insecticides with strong affinities for the insect-selective nicotinic acetylcholine receptor. These provide insect control by hyperstimulating insect nerves and are used for agricultural pest management. However, it has also been reported that ACE and IMI affect mammalian reproductive function. We determined the effects of ACE and IMI on the in vitro maturation of porcine oocytes. Significant decreases in nuclear maturation rates were observed in the ACE or IMI-exposed groups. Also, in matured oocytes from the ACE or IMI-exposed groups, irregular chromosomes were observed. Our results suggest that ACE and IMI exposure was detrimental to porcine oocytes and the extent of the effects depends on the concentration of exposure.

  9. Prevalence and incidence of intramammary infections in lactating dairy goats.

    PubMed

    McDougall, S; Malcolm, D; Prosser, Cg

    2014-05-01

    To determine the prevalence of intramammary infection (IMI) of lactating dairy goats between 0 and 4 days postpartum, the prevalence and incidence rate of new IMI at Weeks 2, 14 and 27 of lactation, and the relationship between herd-level prevalence of IMI and bulk tank somatic cell count (BTSCC). Milk samples were collected from 8% of a herd (total 624 does) from 18 dairy goat herds in the Waikato region of New Zealand, for bacteriology and somatic cell count (SCC) determination, from both glands within 4 days of kidding (Week 0) and again at Weeks 2, 14 and 27. Prevalence of IMI was determined at each time point and incidence rate calculated for Weeks 0-2, 2-14, and 14-27. Greenwood and Reed-Frost models were compared for estimation of the transmission parameter for all pathogens, and for Staphylococcus aureus, coagulase negative staphylococci (CNS) and Corynebacterium spp. separately. Bacteria were isolated from 1,122/4,814 (23.3%) glands, with CNS (13.4%) and Corynebacterium spp. (7.3%) being the most common isolates. Prevalence of any IMI increased with stage of lactation, varied among herds, and increased with age (all p<0.05). Incidence rate was 80, 24 and 7 new IMI/10,000 gland days for Weeks 0-2, 2-14 and 14-27, respectively. Incidence rate for any IMI increased with age and with the presence of an IMI in the contralateral gland, and varied among herds (p<0.001). The transmission of each pathogen was better modelled assuming contagiousness (Reed-Frost models), than not (Greenwood models). At gland level, IMI increased SCC at all stages of lactation (p<0.001). The gland prevalence of IMI within herds was positively associated with ln BTSCC at Week 2 (p=0.02), but not Weeks 14 or 27 (p>0.05). Prevalence of IMI increased with stage of lactation, but the highest incidence rate of new IMI occurred in early lactation. Models accounting for the contagious nature of infection fitted better than those not accounting for contagiousness. BTSCC was only associated with prevalence of IMI in early lactation. Reduction of BTSCC in dairy goats may be best achieved by minimising the prevalence and incidence of new IMI in early lactation. Further studies are required to define management factors associated with the between herd, and stage of lactation, effects on prevalence and incidence rate in order to reduce BTSCC throughout lactation.

  10. Variation in the post-mating fitness landscape in fruit flies.

    PubMed

    Fricke, C; Chapman, T

    2017-07-01

    Sperm competition is pervasive and fundamental to determining a male's overall fitness. Sperm traits and seminal fluid proteins (Sfps) are key factors. However, studies of sperm competition may often exclude females that fail to remate during a defined period. Hence, the resulting data sets contain fewer data from the potentially fittest males that have most success in preventing female remating. It is also important to consider a male's reproductive success before entering sperm competition, which is a major contributor to fitness. The exclusion of these data can both hinder our understanding of the complete fitness landscapes of competing males and lessen our ability to assess the contribution of different determinants of reproductive success to male fitness. We addressed this here, using the Drosophila melanogaster model system, by (i) capturing a comprehensive range of intermating intervals that define the fitness of interacting wild-type males and (ii) analysing outcomes of sperm competition using selection analyses. We conducted additional tests using males lacking the sex peptide (SP) ejaculate component vs. genetically matched (SP + ) controls. This allowed us to assess the comprehensive fitness effects of this important Sfp on sperm competition. The results showed a signature of positive, linear selection in wild-type and SP + control males on the length of the intermating interval and on male sperm competition defence. However, the fitness surface for males lacking SP was distinct, with local fitness peaks depending on contrasting combinations of remating intervals and offspring numbers. The results suggest that there are alternative routes to success in sperm competition and provide an explanation for the maintenance of variation in sperm competition traits. © 2017 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

  11. Induction of P450 genes in Nilaparvata lugens and Sogatella furcifera by two neonicotinoid insecticides.

    PubMed

    Yang, Yuan-Xue; Yu, Na; Zhang, Jian-Hua; Zhang, Yi-Xi; Liu, Ze-Wen

    2018-06-01

    Nilaparvata lugens and Sogatella furcifera are two primary planthoppers on rice throughout Asian countries and areas. Neonicotinoid insecticides, such as imidacloprid (IMI), have been extensively used to control rice planthoppers and IMI resistance consequently occurred with an important mechanism from the over-expression of P450 genes. The induction of P450 genes by IMI may increase the ability to metabolize this insecticide in planthoppers and increase the resistance risk. In this study, the induction of P450 genes was compared in S. furcifera treated with IMI and nitromethyleneimidazole (NMI), in two planthopper species by IMI lethal dose that kills 85% of the population (LD 85 ), and in N. lugens among three IMI doses (LD 15 , LD 50 and LD 85 ). When IMI and NMI at the LD 85 dose were applied to S. furcifera, the expression changes in most P450 genes were similar, including the up-regulation of nine genes and down-regulation of three genes. In terms of the expression changes in 12 homologous P450 genes between N. lugens and S. furcifera treated with IMI at the LD 85 dose, 10 genes had very similar patterns, such as up-regulation in seven genes, down-regulation in one gene and no significant changes in two genes. When three different IMI doses were applied to N. lugens, the changes in P450 gene expression were much different, such as up-regulation in four genes at all doses and dose-dependent regulation of the other nine genes. For example, CYP6AY1 could be induced by all IMI doses, while CYP6ER1 was only up-regulated by the LD 50 dose, although both genes were reported important in IMI resistance. In conclusion, P450 genes in two planthopper species showed similar regulation patterns in responding to IMI, and the two neonicotinoid insecticides had similar effects on P450 gene expression, although the regulation was often dose-dependent. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  12. Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

    PubMed Central

    Chang, Xiubao; Zhu, Yuanxiao; Shi, Changxin; Stewart, A. Keith

    2014-01-01

    Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields. PMID:24374776

  13. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.

    PubMed

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    2016-07-01

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.

  14. A strain-, cow-, and herd-specific bio-economic simulation model of intramammary infections in dairy cattle herds.

    PubMed

    Gussmann, Maya; Kirkeby, Carsten; Græsbøll, Kaare; Farre, Michael; Halasa, Tariq

    2018-07-14

    Intramammary infections (IMI) in dairy cattle lead to economic losses for farmers, both through reduced milk production and disease control measures. We present the first strain-, cow- and herd-specific bio-economic simulation model of intramammary infections in a dairy cattle herd. The model can be used to investigate the cost-effectiveness of different prevention and control strategies against IMI. The objective of this study was to describe a transmission framework, which simulates spread of IMI causing pathogens through different transmission modes. These include the traditional contagious and environmental spread and a new opportunistic transmission mode. In addition, the within-herd transmission dynamics of IMI causing pathogens were studied. Sensitivity analysis was conducted to investigate the influence of input parameters on model predictions. The results show that the model is able to represent various within-herd levels of IMI prevalence, depending on the simulated pathogens and their parameter settings. The parameters can be adjusted to include different combinations of IMI causing pathogens at different prevalence levels, representing herd-specific situations. The model is most sensitive to varying the transmission rate parameters and the strain-specific recovery rates from IMI. It can be used for investigating both short term operational and long term strategic decisions for the prevention and control of IMI in dairy cattle herds. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Fate and effect of imidacloprid on vermicompost-amended soils under dissimilar conditions: Risk for soil functions, structure, and bacterial abundance.

    PubMed

    Castillo Diaz, Jean Manuel; Martin-Laurent, Fabrice; Beguet, Jérèmie; Nogales, Rogelio; Romero, Esperanza

    2017-02-01

    The fate and impact of pesticide on soil depend partly on the agricultural practices, such as prior treatment with pesticide and/or organic amendments. As a means of determining how the previous soil conditions can affect the fate of imidacloprid (IMI) and its effect on soil functions, experiments were made with soil samples, double-amended or not with either vine-shoot (W) or olive cake (O) vermicompost or contaminated or not with IMI. These soil samples, incubated for 3months, were placed in two microcosms (M1 with the pre-amended soils and M2 with the pre-exposed soils), treated with IMI and amended with vermicomposts and then incubated for 3months. The IMI distribution on soil fractions, sorption processes, dissipation kinetics, and biochemical as well as genetic structure and bacterial abundance were determined to assess the fate and impact of IMI on the soil. The addition of W vermicompost to the soil reduced the IMI availability. The dissipation kinetic in soils from M1 and M2 followed, respectively, a single first-order and a double first-order in parallel models. The lowest IMI persistence corresponded to the soil from M2 amended with O-vermicompost with DT50 and DT90 values of 67d and 265d, while in the other soils 90% dissipation required >512d. The vermicomposts-amended contaminated soils increased the dehydrogenase activity by 2- and 4-fold respect the control soils. However, the urease activity decreased due to the IMI influence. The changes in the bacterial community in the contaminated soil amended with O-vermicompost during incubation were correlated with the dissipation rate constant of IMI, suggesting a better tolerance of microorganisms to IMI. Thus, in the soil contaminated with IMI, the amendment with the vermicompost from olive cake can mitigate the impact of this insecticide on soil functions and promote its depuration capability while minimizing environmental risks. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Toxicokinetics of the neonicotinoid insecticide imidacloprid in rainbow trout (Oncorhynchus mykiss)

    EPA Science Inventory

    Imidacloprid (IMI) is the largest selling insecticide internationally. Little is known about the toxicokinetics of IMI in fish, however. In vivo time-course studies were conducted to study the distribution and elimination of IMI in rainbow trout. Animals confined to respiromet...

  17. Randomized trial of intensive motivational interviewing for methamphetamine dependence.

    PubMed

    Polcin, Douglas L; Bond, Jason; Korcha, Rachael; Nayak, Madhabika B; Galloway, Gantt P; Evans, Kristy

    2014-01-01

    An intensive, 9-session motivational interviewing (IMI) intervention was assessed using a randomized clinical trial of 217 methamphetamine (MA) dependent individuals. Intensive motivational interviewing (IMI) was compared with a single standard session of MI (SMI) combined with eight nutrition education sessions. Interventions were delivered weekly over 2 months. All study participants also received standard outpatient group treatment three times per week. Both study groups showed significant decreases in MA use and Addiction Severity Index drug scores, but there were no significant differences between the two groups. However, reductions in Addiction Severity Index psychiatric severity scores and days of psychiatric problems during the past 30 days were found for clients in the IMI group but not the SMI group. SMI may be equally beneficial to IMI in reducing MA use and problem severity, but IMI may help alleviate co-occurring psychiatric problems that are unaffected by shorter MI interventions. Additional studies are needed to assess the problems, populations, and contexts for which IMI is effective.

  18. Biological Control of Alternaria Fruit Rot of Chili by Trichoderma Species under Field Conditions

    PubMed Central

    Rahman, M. A.; Alam, M. Firoz

    2010-01-01

    Trichoderma strains were evaluated under field conditions to assay their efficacy in suppressing Alternaria fruit rot disease and promoting chili plant growth. The experiment was conducted at the Botanical Garden, Rajshahi University, Bangladesh from July 2006 to March 2007. Application of Trichoderma harzianum IMI 392432 significantly (p = 0.05) suppressed the disease compared to Alternaria tenuis (T2) treatment and improved both growth and yield. The treatment T4 (T. harzianum IMI-392432 + A. tenuis) was most effective in reducing disease percentage (72.27%) compared to A. tenuis (T1) treatment. The highest seed germination rate (85.56%) and the highest growth and yield (12.5 g/plant) was also recorded in the same treatment (T4), followed by T5 (T. harzianum IMI-392433 000000 + A. tenuis), T6 (T. harzianum IMI-392434 +A. tenuis), T2 (T. virens IMI-392430 + A. tenuis), and T3 (T. pseudokoningii IMI-392431 +A. tenuis) treatment, while single treatment with A. tenuis significantly decreased these values. PMID:23956637

  19. Effects of co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats.

    PubMed

    Lafi, Bornia; Chaâbane, Mariem; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Ketata Bouaziz, Hanen; Zeghal, Najiba

    2018-05-01

    Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA 3 ) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA 3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA 3 (200 mg/L) via drinking water. IMI associated or no with GA 3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA 3 -induced nephrotoxicity. Co-exposure to IMI and GA 3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

  20. Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids

    PubMed Central

    Boyd, David A.; Mataseje, Laura F.; Davidson, Ross; Delport, Johannes A.; Fuller, Jeff; Hoang, Linda; Lefebvre, Brigitte; Levett, Paul N.; Roscoe, Diane L.; Willey, Barbara M.

    2017-01-01

    ABSTRACT Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A blaNMC-A or blaIMI-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, blaNMC-A was highly associated with Enterobacter ludwigii. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (n = 10), IMI-1 (n = 5), and IMI-9 (n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, blaIMI-5 and blaIMI-6, were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring blaNMC-A/IMI-type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential. PMID:28223374

  1. Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids.

    PubMed

    Boyd, David A; Mataseje, Laura F; Davidson, Ross; Delport, Johannes A; Fuller, Jeff; Hoang, Linda; Lefebvre, Brigitte; Levett, Paul N; Roscoe, Diane L; Willey, Barbara M; Mulvey, Michael R

    2017-05-01

    Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI -type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A ( n = 10), IMI-1 ( n = 5), and IMI-9 ( n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla IMI-5 and bla IMI-6 , were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI -type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential. © Crown copyright 2017.

  2. Effects of Sublethal Doses of Imidacloprid on Young Adult Honeybee Behaviour.

    PubMed

    Mengoni Goñalons, Carolina; Farina, Walter Marcelo

    2015-01-01

    Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance.

  3. Effects of Sublethal Doses of Imidacloprid on Young Adult Honeybee Behaviour

    PubMed Central

    Mengoni Goñalons, Carolina; Farina, Walter Marcelo

    2015-01-01

    Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance. PMID:26488410

  4. Pathogen group specific risk factors for clinical mastitis, intramammary infection and blind quarters at the herd, cow and quarter level in smallholder dairy farms in Jimma, Ethiopia.

    PubMed

    Tolosa, T; Verbeke, J; Ayana, Z; Piepers, S; Supré, K; De Vliegher, S

    2015-07-01

    A cross-sectional study on clinical mastitis, intramammary infection (IMI) and blind quarters was conducted on 50 smallholder dairy farms in Jimma, Ethiopia. A questionnaire was performed, and quarters of 211 cows were sampled and bacteriologically cultured. Risk factors at the herd, cow, and quarter level for clinical mastitis and (pathogen-specific) intramammary infection were studied using multilevel modeling. As well, factors associated with quarters being blind were studied. Eleven percent of the cows and 4% of the quarters had clinical mastitis whereas 85% of the cows and 51% of the quarters were infected. Eighteen percent of the cows had one or more blind quarter(s), whereas 6% of the quarters was blind. Non-aureus staphylococci were the most frequently isolated pathogens in both clinical mastitis cases and IMI. The odds of clinical mastitis was lower in herds where heifers were purchased in the last year [odds ratio (OR) with 95% confidence interval: 0.11 (0.01-0.90)], old cows (>4 years) [OR: 0.45 (0.18-1.14)], and quarters not showing teat injury [OR: 0.23 (0.07-0.77)]. The odds of IMI caused by any pathogen was higher in herds not practicing teat drying before milking (opposed to drying teats with 1 towel per cow) [OR: 1.68 (1.05-2.69)], cows in later lactation (>180 DIM opposed to ≤90 DIM) [OR: 1.81 (1.14-2.88)], cows with a high (>3) body condition score (BCS) [OR: 1.57 (1.06-2.31)], right quarters (opposed to a left quarter position) [OR: 1.47 (1.10-1.98)], and quarters showing teat injury [OR: 2.30 (0.97-5.43)]. Quarters of cows in herds practicing bucket-fed calf feeding (opposed to suckling) had higher odds of IMI caused by Staphylococcus aureus [OR: 6.05 (1.31-27.90)]. Except for BCS, IMI caused by non-aureus staphylococci was associated with the same risk factors as IMI caused by any pathogen. No access to feed and water immediately after milking [OR: 2.41 (1.26-4.60)], higher parity [OR: 3.60 (1.20-10.82)] and tick infestation [OR: 2.42 (1.02-5.71)] were risk factors for quarters being blind. In conclusion, replacement of old cows, prevention of teat injuries/lesions, drying teats with 1 towel per cow before milking, improving fertility in order to shorten the lactation period, allowing (restricted) suckling, access to feed and water immediately after milking, and improving tick control could improve udder health in Jimma. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The innovative medicines initiative: a European response to the innovation challenge.

    PubMed

    Goldman, M

    2012-03-01

    The Innovative Medicines Initiative (IMI) was launched in 2008 as a large-scale public-private partnership between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA). With a total budget of €2 billion, the IMI aims to boost the development of new medicines across Europe by implementing new collaborative endeavors between large pharmaceutical companies and other key actors in the health-care ecosystem, i.e., academic institutions, small and medium enterprises, patients, and regulatory authorities. Projects conducted by IMI consortia have already delivered meaningful results, providing proof-of-concept evidence for the efficiency of this new model of collaboration. In this article we review recent achievements of the IMI consortia and discuss the growing interest in the IMI as a best-practice model to reinvigorate drug development.

  6. Epidemiology, outcomes, and mortality predictors of invasive mold infections among transplant recipients: a 10-year, single-center experience.

    PubMed

    Neofytos, D; Treadway, S; Ostrander, D; Alonso, C D; Dierberg, K L; Nussenblatt, V; Durand, C M; Thompson, C B; Marr, K A

    2013-06-01

    The epidemiology of invasive mold infections (IMI) in transplant recipients differs based on geography, hosts, preventative strategies, and methods of diagnosis. We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients in the era of "classic" culture-based diagnostics (2000-2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005. In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients was 49, 2, 11, and 10 per 1000 person-years, respectively. The observed rate of IMI among human leukocyte antigen-matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P < 0.05). The 12-week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P = 0.007) and SOT (OR: 0.22, P = 0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P = 0.007) and elevated bilirubin (OR: 5.7, P = 0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively. During the era of culture-based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed. © 2013 John Wiley & Sons A/S.

  7. Facile Synthesis of Smart Nanocontainers as Key Components for Construction of Self-Healing Coating with Superhydrophobic Surfaces.

    PubMed

    Liang, Yi; Wang, MingDong; Wang, Cheng; Feng, Jing; Li, JianSheng; Wang, LianJun; Fu, JiaJun

    2016-12-01

    SiO2-imidazoline nanocomposites (SiO2-IMI) owning high loading capacity of corrosion inhibitor, 1-hexadecyl-3-methylimidazolium bromide (HMID), and a special acid/alkali dual-stimuli-accelerated release property have been synthesized via a one-step modified Stöber method. SiO2-IMI were uniformly distributed into the hydrophobic SiO2 sol to construct "host"-"guest" feedback active coating with a superhydrophobic surface (SiO2-IMI@SHSC) on aluminium alloy, AA2024, by dip-coating technique. SiO2-IMI as "guest" components have good compatibility with "host" sol-gel coating, and more importantly, once localized corrosion occurs on the surface of AA2024, SiO2-IMI can simultaneously respond to the increase in environmental pH around corrosive micro-cathodic regions and decrease in pH near micro-anodic regions, promptly releasing HMID to form a compact molecular film on the damaged surface, inhibiting corrosion spread and executing a self-healing function. The scanning vibrating electrode technique (SVET) was applied to illustrate the suppression process of cathodic/anodic corrosion activities. Furthermore, benefiting from the superhydrophobic surface, SiO2-IMI@SHSC remained its protective ability after immersion in 0.5 M NaCl solution for 35 days, which is far superior to the conventional sol-gel coating with the same coating thickness. The facile fabrication method of SiO2-IMI simplifies the construction procedure of SiO2-IMI@SHSC, which have great potential to replace non-environmental chromate conversion coatings for practical use.

  8. Photodegradation of imidacloprid insecticide by Ag-deposited titanate nanotubes: a study of intermediates and their reaction pathways.

    PubMed

    Grover, Inderpreet Singh; Singh, Satnam; Pal, Bonamali

    2014-12-31

    The present work demonstrates the influence of Ag-loading (0.2-1.0 wt %) onto sodium titanate nanotubes (TNT) for complete photomineralization of the neurotoxic imidacloprid (IMI) insecticide under UV light illumination. It has been observed that degradation of IMI follows pseudo-first-order kinetics, where 0.5 wt % Ag-loaded TNT exhibited highest apparent rate constant (2.2 × 10(-2) min(-1)) and corresponding least half-life (t1/2) of 31 min for IMI relative to bare P25-TiO2 (3.4 × 10(-3) min(-1), t1/2 = 230 min). The mineralization of IMI intermediates to CO2 during its photooxidation has been described by time course GC-MS and GC analysis and has been correlated with the kinetic analysis. The investigation for the role and quantitative estimation of the fate of heteroatoms (N, O, and Cl) present in IMI revealed an increase in the amount of nitrate, nitrite, and chloride ions with time during its photooxidation. On the basis of these results a mechanistic pathway for photomineralization of IMI is proposed.

  9. [Effect of imidapril on the effective refractory period and sodium current of ventricular noninfarction zone in healed myocardial infarction].

    PubMed

    Li, Yang; Niu, Hui-Yan; Liu, Nian; Zhang, Cun-Tai; Lu, Zai-Ying; Wang, Shi-Wen

    2005-07-01

    To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models. Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded. The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group. IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

  10. Clonal background, resistance gene profile, and porin gene mutations modulate in vitro susceptibility to imipenem/relebactam in diverse Enterobacteriaceae.

    PubMed

    Gomez-Simmonds, Angela; Stump, Stephania; Giddins, Marla J; Annavajhala, Medini K; Uhlemann, Anne-Catrin

    2018-06-11

    Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae harboring bla KPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem(IMI)/cilastatin. We carried out broth microdilution testing to IMI alone or in the presence of 4 μg/mL REL in 154 clinical isolates collected at a New York City hospital with high prevalence of bla KPC including Enterobacter spp. (n=96), K. pneumoniae (n=44), Escherichia coli (n=1), Serratia marcescens (n=9) and Citrobacter spp. (n=4). Resistance gene profiles and presence of major porin gene disruptions were ascertained by whole genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/mL) in 88% of isolates. However, S. marcescens IMI/REL MICs were 4 to 8-fold higher than those of other organisms. Most bla KPC -positive isolates had IMI/REL MICs ≤1 μg/mL (88%), including E. cloacae ST171 (93%) and K. pneumoniae ST258 (82%). Nineteen isolates had IMI/REL MICs ≥2 μg/mL, of which 84% harbored bla KPC and one was bla NDM-1 -positive. Isolates with IMI/REL MICs ≥2 μg/mL versus ≤1 μg/mL were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%, p =0.04), although most S. marcescens isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates including high-risk clones, chromosomal factors impacted IMI/REL susceptibilities and may contribute to elevated MICs in S. marcescens. Copyright © 2018 American Society for Microbiology.

  11. Subclinical and clinical mastitis in heifers following the use of a teat sealant precalving.

    PubMed

    Parker, K I; Compton, C; Anniss, F M; Weir, A; Heuer, C; McDougall, S

    2007-01-01

    This study investigated the effect in heifers of infusion of a bismuth subnitrate teat-canal sealant and bacterial intramammary infection (IMI) precalving on prevalence of postcalving IMI and incidence of clinical mastitis in the first 2 wk postcalving. Glands (n = 1,020) from heifers (n = 255) in 5 seasonally calving, pasture-fed dairy herds were randomly assigned within heifer to 1 of 4 treatment groups (no treatment; mammary gland secretion collection; infusion of a teat sealant; or sample collection with infusion of teat sealant). Heifers within a herd were enrolled on one calendar day, 31 d on average before the planned start of the seasonal calving period. Duplicate milk samples were collected from each gland within 4 d after calving for bacterial culture. Herd owners collected duplicate milk samples, before treatment, for bacterial culture from glands they defined as having clinical mastitis. The gland prevalence of IMI precalving was 15.5% and did not differ between herds. Bacteria isolated precalving included coagulase-negative staphylococci (76.9% of all bacteriologically positive samples), Streptococcus uberis (14.1%), Staphylococcus aureus (5.1%), Corynebacterium spp. (3.8%), and others (0.1%). The presence of an IMI precalving increased the risk of an IMI postcalving 3.6-fold and the risk of clinical mastitis 4-fold, relative to no IMI precalving. Infusion of the teat sealant reduced the risk of postcalving IMI due to Strep. uberis by 84%, and of clinical mastitis by 68%. Sampling the glands precalving had no effect on postcalving IMI or on clinical mastitis incidence. Use of an internal teat canal sealant in heifers precalving may be a useful tool for reducing the risk of subclinical and clinical mastitis in heifers.

  12. Outbreak of IMI-1 Carbapenemase-producing colistin-resistant Enterobacter cloacae on the French island of Mayotte (Indian Ocean).

    PubMed

    Miltgen, Guillaume; Bonnin, Rémy A; Avril, Catherine; Benoit-Cattin, Thierry; Martak, Daniel; Leclaire, Alexandre; Traversier, Nicolas; Roquebert, Bénédicte; Jaffar-Bandjee, Marie-Christine; Lugagne, Nathalie; Filleul, Laurent; Subiros, Marion; de Montera, Anne-Marie; Cholley, Pascal; Thouverez, Michelle; Dortet, Laurent; Bertrand, Xavier; Naas, Thierry; Hocquet, Didier; Belmonte, Olivier

    2018-05-25

    The spread of carbapenemase-producing Enterobacteriaceae (CPE) in the Southwest Indian Ocean islands is poorly known. We describe here an outbreak of colistin-resistant Enterobacter cloacae harboring bla IMI-1 in the French overseas department of Mayotte. Between October 2015 and January 2017, all isolates of imipenem-non-susceptible E. cloacae at the Mayotte Medical Center and University Hospital of Reunion Island were screened for carbapenemase production. Positive isolates were typed by pulsed-field gel electrophoresis and WGS-based MLST and all β-lactamase genes identified by PCR and sequencing. The resistance profiles were determined by agar diffusion and E-tests. Genetic support of the bla IMI-1 gene was determined by WGS. We detected 18 isolates of E.cloacae harboring the bla IMI-1 gene in 17 patients from Mayotte. PFGE analysis showed 16 of the 18 strains to be clonally-related and belonging to sequence type ST820. Based on clinical data, this outbreak most likely had a community origin. The bla IMI-1 gene in the 18 isolates was carried by a new variant of an integrative mobile element involving the Xer recombinases, called EcloIMEX-8. The mcr-1 to mcr-5 genes were absent from the collection. These isolates belong to E. cloacae cluster XI, known to be colistin heteroresistant. We report here the first outbreak of IMI-1-producing Enterobacteriaceae. IMI-1 producers may be under-detected in microbiology laboratories because of their unusual antibiotic resistance profile (resistant to imipenem, but with intermediate resistance to ertapenem and susceptible to extended-spectrum cephalosporins) and the absence of bla IMI-1 in the panel of genes targeted by molecular diagnostic kits. Copyright © 2018. Published by Elsevier B.V.

  13. Perceptible changes in Indian summer monsoon rainfall in relation to Indian Monsoon Index

    NASA Astrophysics Data System (ADS)

    Naidu, C. V.; Dharma Raju, A.; Vinay Kumar, P.; Satyanarayana, G. Ch.

    2017-10-01

    The changes in the summer monsoon rainfall over 30 meteorological subdivisions of India with respect to changes in circulation and the Indian Monsoon Index (IMI) have been studied for the period 1953-2012. The relationship between the IMIs in different months and whole season and the corresponding summer monsoon rainfall is studied and tested. The positive and negative extremes are evaluated basing on the normalized values of the deviations from the mean of the IMI. Composite rainfall distributions over India and the zonal wind distributions in the lower and upper troposphere of IMI's both positive and negative extremes are evaluated separately and discussed. In the recent three decades of global warming, the negative values of IMI in July and August lead to weakening of the monsoon system over India. It is observed that the rainfall variations in the Northeast India are different from the rest of India except Tamil Nadu in general.

  14. Imidacloprid Causes DNA Damage in Fish: Clastogenesis as a Mechanism of Genotoxicity.

    PubMed

    Iturburu, Fernando G; Simoniello, María F; Medici, Sandra; Panzeri, Ana M; Menone, Mirta L

    2018-06-01

    Neonicotinoids are one of the most widely used insecticides in the world. DNA damage is considered an early biological effect which could lead to reproductive and carcinogenic effects. The present study aimed to evaluate DNA damage and bases oxidation as a mechanism of genotoxicity, on the freshwater fish Australoheros facetus acutely exposed to imidacloprid (IMI). The Comet assay with the nuclease ENDO III enzyme was performed for detecting pyrimidine bases oxidation using blood samples. Micronucleus and other nuclear abnormalities frequencies were also quantified. A significant increase of damage index at 100 and 1000 µg/L IMI was detected; while ENDO III score increased from 1 to 1000 µg/L IMI; varying both in a linear concentration-response manner. MN frequency increased in fish exposed to 1000 µg/L IMI. These results show that short-term exposures to environmentally relevant concentrations of IMI could affect the genetic integrity of fishes through oxidative damage.

  15. Co-treatment with imipramine averted haloperidol-instigated tardive dyskinesia: Association with serotonin in brain regions.

    PubMed

    Samad, Noreen; Yasmin, Farzana; Haleem, Darakhshan Jabeen

    2016-11-01

    Outcome of imipramine (IMI) treatment was scrutinized on progression of haloperidol instigated tardive dyskinesia (TD). 0.2 mg/kg/rat dosage of haloperidol provided orally to rats for 2 weeks enhanced vacuous chewing movements that escalated when the process proceeded for 5 weeks. Following 2 weeks co-injection 5 mg/kg dosage of IMI was diminished haloperidol-instigated VCMs and fully averted following five weeks. The potency of 8-OH-DPAT-instigated locomotor activity exhibited higher in saline+haloperidol treated rats while not observed in IMI+ haloperidol treated rats. 8-OH-DPAT-instigated low 5-hydroxytryptamine (5-HT; serotonin) metabolism was higher in saline+ haloperidol treated rats when compare to IMI+ haloperidol treated rats in both regions of brain (striatum and midbrain). It is recommended that IMI possibly competent in averting TD, in cases receiving treatment to antipsychotics.

  16. [Internet- and Mobile Based Psychotherapy for Depression].

    PubMed

    Sander, Lasse; Ebert, David Daniel; Baumeister, Harald

    2017-01-01

    Guided Internet- and mobile-based interventions (IMIs) are an effective and scientifically sound treatment option for depression. Meta-analyses revealed effect sizes comparable to those found for face-to-face treatment as well as pharmacotherapy. Today, most IMIs are based on cognitive behavioral therapy (CBT). While IMIs are well established in healthcare systems of many countries worldwide, Germany is still lagging behind. However, there are an increasing number of model projects trying to implement IMIs into routine healthcare for depression in Germany. Both, service providers and recipients would benefit from transparent quality assurance and data safety guidelines. © Georg Thieme Verlag KG Stuttgart · New York.

  17. A ratiometric strategy -based electrochemical sensing interface for the sensitive and reliable detection of imidacloprid.

    PubMed

    Li, Xueyan; Kan, Xianwen

    2018-04-30

    In this study, a ratiometric strategy-based electrochemical sensor was developed by electropolymerization of thionine (THI) and β-cyclodextrin (β-CD) composite films on a glassy carbon electrode surface for imidacloprid (IMI) detection. THI played the role of an inner reference element to provide a built-in correction. In addition, the modified β-CD showed good selective enrichment for IMI to improve the sensitivity and anti-interference ability of the sensor. The current ratio between IMI and THI was calculated as the detected signal for IMI sensing. Compared with common single-signal sensing, the proposed ratiometric strategy showed a higher linear range and a lower limit of detection of 4.0 × 10-8-1.0 × 10-5 mol L-1 and 1.7 × 10-8 mol L-1, respectively, for IMI detection. On the other hand, the ratiometric strategy endowed the sensor with good accuracy, reproducibility, and stability. The sensor was also used for IMI determination in real samples with satisfactory results. The simple, effective, and reliable way reported in this study can be further used to prepare ratiometric strategy-based electrochemical sensors for the selective and sensitive detection of other compounds with good accuracy and stability.

  18. Knockdown of Fruit Flies by Imidacloprid Nanoaerosol.

    PubMed

    Morozov, Victor N; Kanev, Igor L

    2015-10-20

    This report describes the effects of nanoaerosol particles (NAPs) from imidacloprid (IMI) on fruit flies. NAPs were produced using a newly developed generator which employs electro-hydrodynamic atomization of IMI solution in ethanol. Exposure of Drosophila melanogaster to the IMI NAPs at a concentration of C = 2.7 ± 0.1 ng/cm(3) caused knockdown in half of the flies in T50 = 88 ± 14 min at 22 °C and in T50 = 36 ± 2 min at 33 °C. A number of special experiments precluded IMI volatilization and contact or oral action of IMI upon exposure to the NAPs. It was shown that only the fraction of NAPs in the size range of 7-300 nm is responsible for the knockdown and that dependence of T50 on the NAPs' fraction mass follows Haber's rule, C × T50 = const. Comparison with the oral doses obtained when flies were fed an IMI-sucrose mixture revealed that the inhaled doses that caused knockdown were 2 orders of magnitude lower than the oral ones. This new technology may be used to quickly eliminate insects with nanoaerosols of nonvolatile insecticides in greenhouses and other closed environments.

  19. The Street Level Built Environment and Physical Activity and Walking: Results of a Predictive Validity Study for the Irvine Minnesota Inventory

    ERIC Educational Resources Information Center

    Boarnet, Marlon G.; Forsyth, Ann; Day, Kristen; Oakes, J. Michael

    2011-01-01

    The Irvine Minnesota Inventory (IMI) was designed to measure environmental features that may be associated with physical activity and particularly walking. This study assesses how well the IMI predicts physical activity and walking behavior and develops shortened, validated audit tools. A version of the IMI was used in the Twin Cities Walking…

  20. A novel extended architecture with 4 6·6 4 topology based on mixed-valence Wells-Dawson arsenotungstate and mixed-ligand Cu(I) units

    NASA Astrophysics Data System (ADS)

    Tong, Ruizhan; Ren, Xiaoyu; Li, Zuoxi; Liu, Bin; Hu, Huaiming; Xue, Ganglin; Fu, Feng; Wang, Jiwu

    2010-09-01

    A novel inorganic-organic hybrid compound based on mixed-valence Wells-Dawson arsenotungstate and mixed-ligand Cu(I) units, Cu 8I(imi) 4(bpy) 6(H 2O)[As 2VW 2VW 16VlO 62]·2H 2O ( 1) (bpy=4,4'-bipydine; imi=imidazole), has been hydrothermally synthesized and characterized by elemental analysis, IR spectroscopy, thermal gravimetric analysis, luminescent spectrum and single crystal X-ray diffraction. Single-crystal X-ray diffraction revealed that four terminal and three bridging oxygen atoms of the Wells-Dawson cluster are coordinated to Cu(I) ions and form an unprecedented hepta-supporting polyoxometalate. The functionalized arsenotungstates are further connected by two kinds of tridentate linkers, Imi-Cu-(bpy)-Cu-(bpy)-Cu-(bpy)-Cu-Imi and Imi-Cu-(bpy)-Cu-(bpy)-Cu-H 2O, to construct a 3D framework with 4 6·6 4 topology. The hybrid material has an intense emission at about 397 nm.

  1. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma

    PubMed Central

    Zhu, Yuan Xiao; Kortuem, K. Martin; Stewart, A. Keith

    2014-01-01

    Although several mechanisms have been proposed to explain the activity of thalidomide, lenalidomide and pomalidomide in multiple myeloma (MM), including demonstrable anti-angiogenic, anti-proliferative and immunomodulatory effects, the precise cellular targets and molecular mechanisms have only recently become clear. A landmark study recently identified cereblon (CRBN) as a primary target of thalidomide teratogenicity. Subsequently it was demonstrated that CRBN is also required for the anti-myeloma activity of thalidomide and related drugs, the so-called immune-modulatory drugs (IMiDs). Low CRBN expression was found to correlate with drug resistance in MM cell lines and primary MM cells. One of the downstream targets of CRBN identified is interferon regulatory factor 4 (IRF4), which is critical for myeloma cell survival and is down-regulated by IMiD treatment. CRBN is also implicated in several effects of IMiDs, such as down-regulation of tumor necrosis factor-α (TNF-α) and T cell immunomodulatory activity, demonstrating that the pleotropic actions of the IMiDs are initiated by binding to CRBN. Future dissection of CRBN downstream signaling will help to delineate the underlying mechanisms for IMiD action and eventually lead to development of new drugs with more specific anti-myeloma activities. It may also provide a biomarker to predict IMiD response and resistance. PMID:22966948

  2. The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

    PubMed

    Pérez-Iglesias, J M; Ruiz de Arcaute, C; Nikoloff, N; Dury, L; Soloneski, S; Natale, G S; Larramendy, M L

    2014-06-01

    The neonicotinoid insecticide imidacloprid (IMI) affects the insect central nervous system and is successfully applied to control pests for a variety of agricultural crops. In the current study, acute toxicity and genotoxicity of the IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI) was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under laboratory conditions. A lethal effect was evaluated as the end point for lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Sublethal end points were assayed within the 12.5-37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage 36 (range, 35-37) according to the classification proposed by Gosner. Lethality studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear abnormalities were induced. Increase of the genetic damage index was observed at 48h of treatment within the 12.5-37.5mg/L concentration range, whereas an increased frequency of DNA damage was observed only in tadpoles treated with 37.5mg/L IMI for 96h. This study represents the first evidence of the acute lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species native to Argentina under laboratory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Concentration of selected sulfonylurea, sulfonamide, and imidazolinone herbicides, other pesticides, and nutrients in 71 streams, 5 reservoir outflows, and 25 wells in the Midwestern United States, 1998

    USGS Publications Warehouse

    Battaglin, William A.; Furlong, Edward T.; Burkhardt, Mark R.

    2001-01-01

    Sulfonylurea (SU), sulfonamide (SA), and imidazolinone (IMI) herbicides are recently developed herbicides that function by inhibiting the action of a key plant enzyme, stopping plant growth, and eventually killing the plant. These compounds generally have low mammalian toxicity, but crop and non-crop plants demonstrate a wide range in sensitivity to SUs, SAs, and IMIs, with over a 10,000-fold difference in observed toxicity levels for some compounds. SUs, SAs, and IMIs are applied either pre- or post-emergence to crops commonly at 1/50th or less of the rate of other herbicides. Little is known about their occurrence, fate, or transport in surface water or ground water in the United States. To obtain information on the occurrence of SU, SA, and IMI herbicides in the Midwestern United States, 214 water samples were collected from 76 surface-water and 25 ground-water sites in 1998. These samples were analyzed for 16 SU, SA, and IMI herbicides by using highperformance liquid chromatography/mass spectrometry. Samples also were analyzed for 46 pesticides and pesticide degradation products and 13 herbicides and 10 herbicide degradates. At least 1 of the 16 SUs, SAs, or IMIs was detected at or above the method reporting limit of 0.010 microgram per liter (ug/L) in 83 percent of 133 stream samples. Imazethapyr was detected most frequently (69 percent of samples), followed by flumetsulam (65 percent of samples) and nicosulfuron (53 percent of samples). At least one SU, SA, or IMI herbicide was detected at or above the method reporting limit in 6 of 8 reservoir samples and 5 of 25 ground-water samples. SU, SA, and IMI herbicides occurred less frequently and at a fraction (often 1/50th or less) of the concentrations of other herbicides such as atrazine. Acetochlor, atrazine, cyanazine, and metolachlor were all detected in 95 percent or more of 136 stream samples.

  4. Occurrence of sulfonylurea, sulfonamide, imidazolinone, and other herbicides in rivers, reservoirs and ground water in the Midwestern United States, 1998

    USGS Publications Warehouse

    Battaglin, W.A.; Furlong, E.T.; Burkhardt, M.R.; Peter, C.J.

    2000-01-01

    Sulfonylurea (SU), sulfonamide (SA), and imidazolinone (IMI) herbicides are relatively new classes of chemical compounds that function by inhibiting the action of a plant enzyme, stopping plant growth, and eventually killing the plant. These compounds generally have low mammalian toxicity, but plants demonstrate a wide range in sensitivity to SUs, SAs, and IMIs with over a 10000-fold difference in observed toxicity levels for some compounds. SUs, SAs, and IMIs are applied either pre- or post-emergence to crops commonly at 1/50th or less of the rate of other herbicides. Little is known about their occurrence, fate, or transport in surface water or ground water in the USA. To obtain information on the occurrence of SU, SA, and IMI herbicides in the Midwestern United States, 212 water samples were collected from 75 surface-water and 25 ground-water sites in 1998. These samples were analyzed for 16 SU, SA and IMI herbicides by USGS Methods Research and Development Program staff using high-performance liquid chromatography/mass spectrometry. Samples were also analyzed for 47 pesticides or pesticide degradation products. At least one of the 16 SUs, SAs or IMIs was detected above the method reporting limit (MRL) of 0.01 ??g/l in 83% of 130 stream samples. Imazethapyr was detected most frequently (71% of samples) followed by flumetsulam (63% of samples) and nicosulfuron (52% of samples). The sum of SU, SA and IMI concentrations exceeded 0.5 ??g/l in less than 10% of stream samples. Acetochlor, alachlor, atrazine, cyanazine and metolachlor were all detected in 90% or more of 129 stream samples. The sum of the concentration of these five herbicides exceeded 50 ??g/l in approximately 10% of stream samples. At least one SU, SA, or IMI herbicide was detected above the MRL in 24% of 25 ground-water samples and 86% of seven reservoir samples. Copyright (C) 2000 Elsevier Science B.V.

  5. Both point mutations and low expression levels of the nicotinic acetylcholine receptor β1 subunit are associated with imidacloprid resistance in an Aphis gossypii (Glover) population from a Bt cotton field in China.

    PubMed

    Chen, Xuewei; Li, Fen; Chen, Anqi; Ma, Kangsheng; Liang, Pingzhuo; Liu, Ying; Song, Dunlun; Gao, Xiwu

    2017-09-01

    Aphis gossypii Glover is a destructive pest of numerous crops throughout the world. Although the expansion of Bt cotton cultivation has helped to control some insect pests, the damage from cotton aphids has not been mitigated. The evolution of aphid resistance to imidacloprid has made its chemical control more difficult since its introduction in 1991. Field populations of A. gossypii that were collected from different transgenic (Bt) cotton planting areas of China in 2014 developed different levels of resistance to imidacloprid. The IMI_R strain has developed high resistance to imidacloprid with the resistance ratio >1200-fold. Compared with the susceptible IMI_S strain, the IMI_R strain also developed a high level cross resistance to sulfoxaflor and acetamiprid. The limited synergism with either PBO or DEF suggests that resistance may be due to the site mutation of molecular target rather than to enhanced detoxification. Three target-site mutations within the nicotinic acetylcholine receptor (nAChR) β1 subunit were detected in the IMI_R strain. The R81T mutation has been reported to be responsible for imidacloprid resistance in A. gossypii and M. persicae. Both V62I and K264E were first detected in A. gossypii. These point mutations are also present in field populations, suggesting that they play a role in the resistance to imidacloprid. Furthermore, the expression level of transcripts encoding β1 subunit was decreased significantly in the IMI_R strain compared with the IMI_S strain, suggesting that both point mutations and the down-regulation of nAChR β1 subunit expression may be involved in the resistance mechanism for imidacloprid in A. gossypii. These results should be useful for the management of imidacloprid-resistant cotton aphids in Bt cotton fields in China. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

    PubMed

    Kowalec, Piotr; Grynberg, Marcin; Pająk, Beata; Socha, Anna; Winiarska, Katarzyna; Fronk, Jan; Kurlandzka, Anna

    2015-09-01

    Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Inner Magnetosphere Imager (IMI) instrument heritage

    NASA Technical Reports Server (NTRS)

    Wilson, G. R.

    1993-01-01

    This report documents the heritage of instrument concepts under consideration for the Inner Magnetosphere Imager (IMI) mission. The proposed IMI will obtain the first simultaneous images of the component regions of the inner magnetosphere and will enable scientists to relate these global images to internal and external influences as well as local observations. To obtain simultaneous images of component regions of the inner magnetosphere, measurements will be made of: (1) the ring current and inner plasma sheet using energetic neutral atoms; (2) the plasmasphere using extreme ultraviolet; (3) the electron and proton auroras using far ultraviolet and x rays; and (4) the geocorona using FUV. Instrument concepts that show heritage and traceability to those that will be required to meet the IMI measurement objectives are described.

  8. Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

    PubMed

    Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

    2018-01-01

    Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure ( p <  0.05), iNOS expression was up-regulated with both low and high doses of IMI and in a time-dependent manner ( p <  0.05, p <  0.01, p <  0.001), CYP1A expression was not significantly changed regardless of the dose of IMI and exposure time ( p >  0.05) except with low and high doses of IMI for 96 h ( p <  0.05), and lastly, MT1 gene expression was up-regulated only in the brain with low doses of IMI for 96 h and high doses of IMI for 48 h, 72 h and 96 h exposure ( p <  0.05, p <  0.01). Our results indicated that acute IMI exposure moderately induce apoptosis in the brain but caused severe histopathological lesions, inflammation, and oxidative stress in the gills, liver, and brain of the common carp.

  9. N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: behavioral and biochemical analyses in rats.

    PubMed

    Smaga, Irena; Pomierny, Bartosz; Krzyżanowska, Weronika; Pomierny-Chamioło, Lucyna; Miszkiel, Joanna; Niedzielska, Ewa; Ogórka, Agata; Filip, Małgorzata

    2012-12-03

    The growing body of evidence implicates the significance of oxidative stress in the pathophysiology of depression. The aim of this paper was to examine N-acetylcysteine (NAC) - a putative precursor of the most important tissue antioxidant glutathione - in an animal model of depression and in ex vivo assays to detect oxidative stress parameters. Imipramine (IMI), a classical and clinically-approved antidepressant drug was also under investigation. Male Wistar rats which underwent either bulbectomy (BULB; removal of the olfactory bulbs) or sham surgery (SHAM; olfactory bulbs were left undestroyed) were treated acutely or repeatedly with NAC (50-100mg/kg, ip) or IMI (10mg/kg, ip). Following 10-daily injections with NAC or IMI or their solvents, or 9-daily injections with a corresponding solvent plus acute NAC or acute IMI forced swimming test on day 10, and locomotor activity were performed; immediately after behavioral tests animals were decapitated. Biochemical tests (the total antioxidant capacity - TAC and the superoxide dismutase activity - SOD) were performed on homogenates in several brain structures. In behavioral studies, chronic (but not acute) administration of NAC resulted in a dose-dependent reduction in the immobility time seen only in BULB rats while chronic IMI produced a significant decrease in this parameter in both SHAM and BULB animals. On the other hand, chronic administration of NAC and IMI resulted in a significant increase in cellular antioxidant mechanisms (SOD activity) that reversed the effects of BULB in the frontal cortex, hippocampus and striatum. Our study further supports the antidepressant-like activity of NAC and links its effect as well as IMI actions with the enhancement of brain SOD activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Organophosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Di Consiglio, Emma; Meneguz, Annarita; Testai, Emanuela

    2005-06-15

    The drug-toxicant interaction between the antidepressant imipramine (IMI) and three organophosphorothionate pesticides (OPTs), to which humans may be chronically and simultaneously exposed, has been investigated in vitro. Concentrations of IMI (2-400 {mu}M) and OPTs ({<=}10 {mu}M) representative of actual human exposure have been tested with recombinant human CYPs and human liver microsomes (HLM). The different CYPs involved in IMI demethylation to the pharmacologically active metabolite desipramine (DES) were CYP2C19 > CYP1A2 > CYP3A4. The OPTs significantly inhibited (up to >80%) IMI bioactivation catalyzed by the recombinant CYPs tested, except CYP2D6, and by HLM; the inhibition was dose-dependent and started atmore » low pesticide concentrations (0.25-2.5 {mu}M). The OPTs, having lower K {sub m} values, efficiently competed with IMI for the enzyme active site, as in the case of CYP2C19. However, with CYP1A2 and CYP3A4, a time- and NADPH-dependent mechanism-based inactivation also occurred, consistently with irreversible inhibition due to the release of the sulfur atom, binding to the active CYP during OPT desulfuration. At low IMI and OPT concentrations, lower IC50 values have been obtained with recombinant CYP1A2 (0.7-1.1 {mu}M) or with HLM rich in 1A2-related activity (2-10.8 {mu}M). The K {sub i} values (2-14 {mu}M), independent on substrate concentrations, were quite low and similar for the three pesticides. Exposure to OPTs during IMI therapeutic treatments may lead to decreased DES formation, resulting in high plasma levels of the parent drug, eventual impairment of its pharmacological action and possible onset of adverse drug reactions (ADRs)« less

  11. The insecticidal activity and action mode of an imidacloprid analogue, 1-(3-pyridylmethyl)-2-nitroimino-imidazolidine.

    PubMed

    Zhuang, An-Xiang; Zhang, Yi-Xi; Zhang, Hui; Liu, Ze-Wen

    2016-10-01

    Neonicotinoids, such as imidacloprid, are key insecticides extensively used for control of Nilaparvata lugens. However, imidacloprid resistance has been reported in many Asian countries in recent years. To understand the roles of the chlorine atom of pyridyl group on insecticidal activity and resistance, the atom was removed to generate an imidacloprid analogue DC-Imi (DesChlorine Imidacloprid). DC-Imi showed significantly higher toxicity than imidacloprid in the susceptible strain of N. lugens, but had medium level cross-resistance in an imidacloprid-resistant strain. In Xenopus oocyte expressed nicotinic acetylcholine receptors (nAChRs) Nlα1/rβ2, the inward currents evoked by DC-Imi were detected and could be blocked by typical nAChRs antagonist dihydro-β-erythroidine (DHβE), which demonstrated that DC-Imi acted as an agonist on insect nAChRs. The efficacy of DC-Imi on Nlα1/rβ2 was 1.8-fold higher than that of imidacloprid. In addition, the influence of an imidacloprid resistance associated mutation (Y151S) on agonist potencies was evaluated. Compared with the wild-type receptor, the mutation reduced maximal inward current of DC-Imi to 55.6% and increased half maximal effective concentration (EC50 ) to 3.53-fold. Compared with imidacloprid (increasing EC50 to 2.38-fold of wild-type receptor), Y151S mutation decreased DC-Imi potency more significantly. The results indicated that the selective and possibly high toxicities could be achieved through the modification of 6-chloro-3-pyridyl group in imidacloprid and other neonicotinoids. © 2015 Institute of Zoology, Chinese Academy of Sciences.

  12. Convergent neuromodulation onto a network neuron can have divergent effects at the network level

    PubMed Central

    Kintos, Nickolas; Nusbaum, Michael P.; Nadim, Farzan

    2016-01-01

    Different neuromodulators often target the same ion channel. When such modulators act on different neuron types, this convergent action can enable a rhythmic network to produce distinct outputs. Less clear are the functional consequences when two neuromodulators influence the same ion channel in the same neuron. We examine the consequences of this seeming redundancy using a mathematical model of the crab gastric mill (chewing) network. This network is activated in vitro by the projection neuron MCN1, which elicits a half-center bursting oscillation between the reciprocally-inhibitory neurons LG and Int1. We focus on two neuropeptides which modulate this network, including a MCN1 neurotransmitter and the hormone crustacean cardioactive peptide (CCAP). Both activate the same voltage-gated current (IMI) in the LG neuron. However, IMI-MCN1, resulting from MCN1 released neuropeptide, has phasic dynamics in its maximal conductance due to LG presynaptic inhibition of MCN1, while IMI-CCAP retains the same maximal conductance in both phases of the gastric mill rhythm. Separation of time scales allows us to produce a 2D model from which phase plane analysis shows that, as in the biological system, IMI-MCN1 and IMI-CCAP primarily influence the durations of opposing phases of this rhythm. Furthermore, IMI-MCN1 influences the rhythmic output in a manner similar to the Int1-to-LG synapse, whereas IMI-CCAP has an influence similar to the LG-to-Int1 synapse. These results show that distinct neuromodulators which target the same voltage-gated ion channel in the same network neuron can nevertheless produce distinct effects at the network level, providing divergent neuromodulator actions on network activity. PMID:26798029

  13. An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas

    PubMed Central

    Predina, Jarrod D.; Newton, Andrew D.; Xia, Leilei; Corbett, Christopher; Connolly, Courtney; Shin, Michael; Sulyok, Lydia Frezel; Litzky, Leslie; Deshpande, Charuhas; Nie, Shuming; Kularatne, Sumith A.; Low, Philip S.; Singhal, Sunil

    2018-01-01

    Background Clinical applicability of folate receptor-targeted intraoperative molecular imaging (FR-IMI) has been established for surgically resectable pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has not been studied. In this study, we evaluate feasibility of FR-IMI in patients undergoing pulmonary resection for squamous cell carcinomas (SCCs). Methods In a human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent FR-IMI with a near-infrared contrast agent that targets the folate receptor-α (FRα), OTL38. Near-infrared signal from tumors and benign lung was quantified to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression was characterized, and histopathologic correlative analyses were performed to evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to determine patient and histopathologic variables that predict tumor fluorescence. Results 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs in a FRα-dependent manner. FR-IMI was reliable in localizing nodules as small as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in three subjects. Upon evaluation of patient and histopathologic variables, in situ fluorescence was associated with distance from the pleural surface, and was independent of alternative variables including tumor size and metabolic activity. Conclusions This work demonstrates that FR-IMI is potentially feasible in 70% of SCC patients, and that molecular imaging can improve localization during minimally invasive pulmonary resection. These findings complement previous data demonstrating that ∼98% of pulmonary adenocarcinomas are localized during FR-IMI and suggest broad applicability for NSCLC patients undergoing resection. PMID:29568374

  14. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection

    PubMed Central

    Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L.; Brown, Michelle L.; Losada, Maria C.; Pedley, Alison; Kartsonis, Nicholas A.

    2016-01-01

    Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas. In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. PMID:27503659

  15. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection.

    PubMed

    Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L; Brown, Michelle L; Losada, Maria C; Pedley, Alison; Kartsonis, Nicholas A; Paschke, Amanda

    2016-10-01

    Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P < 0.001). The treatment groups were also similar with respect to clinical response at early and late follow-up and microbiological response at all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. ‘Imi Hale – The Native Hawaiian Cancer Awareness, Research, and Training Network: Second-Year Status Report

    PubMed Central

    Braun, Kathryn L.; Tsark, JoAnn; Ann Santos, Lorrie; Abrigo, Lehua

    2010-01-01

    Purpose The purpose of this paper is to describe ‘Imi Hale, a program developed and managed by Native Hawaiians to increase cancer awareness and research capacity among Native Hawaiians. This US subgroup of indigenous people of the Hawaiian islands has disproportionately high rates of cancer mortality and low rates of participation in health and research careers. Methods As a community-based research project, ‘Imi Hale spent its first year gathering data from Native Hawaiians about their cancer awareness and research priorities. These findings guide ‘Imi Hale’s community and scientific advisors, a community-based Institutional Review Board, Na Liko Noelo (budding researchers), and staff in developing and carrying out projects that address these priority areas. Emphasis is placed on transferring skills and resources to Native Hawaiians through training, technical assistance, and mentorship. A biennial survey assesses the extent to which community-based participatory research principles are being followed. Principal Findings By the end of the second year, statewide and island-specific awareness plans were produced, and 9 funded awareness projects are supporting the development and dissemination of Hawaiian health education materials. Research accomplishments include the enrollment of 42 Native Hawaiian Na Liko Noelo (budding researchers), 22 of which are involved in 14 funded research projects. The biennial evaluation survey found that 92% of our advisors felt that ‘Imi Hale was promoting scientifically rigorous research that was culturally appropriate and respectful of Native Hawaiian beliefs, and 96% felt that ‘Imi Hale was following its own principles of community-based participatory research. Conclusion ‘Imi Hale’s community-based approach to promoting cancer awareness will result in a sustainable infrastructure for reducing the cancer burden on Native Hawaiians. PMID:15352771

  17. Adding an Intelligent Tutoring System to an Existing Training Simulation

    DTIC Science & Technology

    2006-01-01

    to apply information in a job should be the goal of training. Also, conventional IMI is not able to meaningfully incorporate use of free - play simulators...incorporating desktop free - play simulators into computer-based training since the software can stand in for a human tutor in all the roles. Existing IMI...2. ITS can integrate free - play simulators and IMI BC2010 ITS DESCRIPTION Overview Figure 3 illustrates the interaction between BC2010, ITS

  18. Epidemiology of Invasive Mold Infections in Allogeneic Stem Cell Transplant Recipients: Biological Risk Factors for Infection According to Time after Transplantation

    PubMed Central

    Garcia-Vidal, Carol; Upton, Arlo; Kirby, Katharine A.; Marr, Kieren A.

    2009-01-01

    Background Invasive mold infections (IMIs) are common in individuals who have undergone hematopoietic stem cell transplantation (HSCT). We sought to determine clinical and biological risk factors for different IMIs during each period (early and late) after allogeneic HSCT. Methods Cases of proven and probable IMI diagnosed in HSCT recipients at the Fred Hutchinson Cancer Research Center (Seattle, WA) from 1 January 1998 through 31 December 2002 were included. Survival was estimated with Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results During the study period, 1248 patients underwent allogeneic HSCT; 163 (13.1%) received a diagnosis of probable or proven IMI. The majority of cases were caused by Aspergillus species (88%). The incidence of IMI caused by other molds remained low (<2%) over the 4-year study period. Risk factors for IMI early after HSCT and late after HSCT differed, with host variables (age) and transplant variables (human leukocyte antigen match) predominating as early risk factors and other clinical complications (graft-versus-host disease and cytomegalovirus disease) predominating later. Biological risk factors that were important during all periods included multiple cytopenias (neutropenia, lymphopenia, and monocytopenia) and iron overload. Conclusions Risk factors for invasive aspergillosis after allogeneic HSCT are multifactorial and differ according to timing after HSCT. Increased attention should be placed on understanding the immunopathogenesis of fungal disease after HSCT. PMID:18781877

  19. Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies.

    PubMed

    Chen, Min; Zhao, Yongfeng; Xu, Chuanxin; Wang, Xian; Zhang, Xianping; Mao, Benyu

    2018-06-01

    The effect of immunomodulatory drugs (IMiDs) on serious infection remains uncertain. We therefore conducted a systematic review and meta-analysis to assess the possible impact of IMiDs on serious infection in patients with multiple myeloma (MM). We searched randomized controlled trials (RCTs) and observational studies from databases that addressed the effect of IMiDs on serious infection in patients with MM. We pooled data from RCTs and observational studies separately and used the GRADE approach to rate the quality of evidence. Rates in patients with individual IMiDs at different treatment status ranged from 7.00 to 23.00%. The use of thalidomide- or lenalidomide-based regimen induction therapy for autologous stem cell transplantation (ASCT)-ineligible patients suggests increase in serious infection (RR = 1.59, 95% CI 1.31-1.93, p < 0.01). Compared to conventional therapy, IMiDs' induction in ASCT-eligible patients significantly decreases the risk of serious infection (RR = 0.82, 95% CI 0.72-0.94, p < 0.01). Lenalidomide-based therapy was associated with a significant increase in risk of serious infection in patients treated compared with conventional therapy (RR = 2.45, 95% CI 1.57-3.83, p < 0.01). The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious infection.

  20. Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin

    PubMed Central

    Ihara, Makoto; Okajima, Toshihide; Yamashita, Atsuko; Oda, Takuma; Hirata, Koichi; Nishiwaki, Hisashi; Morimoto, Takako; Akamatsu, Miki; Ashikawa, Yuji; Kuroda, Shun’ichi; Mega, Ryosuke; Kuramitsu, Seiki; Sattelle, David B.

    2008-01-01

    Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR–neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH–π interactions in the Ls-AChBP–CTD complex than in the Ls-AChBP–IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs. PMID:18338186

  1. Imi Ho'ola post-baccalaureate program: recruitment, retention, and graduation of Asian American and Pacific Islander students in medicine.

    PubMed

    Judd, N L; Sing, P M

    2001-09-01

    Imi Ho'ola has been a successful model for training underrepresented minorities and disadvantaged individuals in medicine at the University of Hawai'i. This program has 28 years of experience assisting students to prepare for, qualify for, and complete the M.D. program, thereby producing medical doctors and other health professionals for Hawai'i, Guam, American Samoa, the U.S. Associated Pacific Islands (USAPI), and the continental U.S. Recently, Imi Ho'ola has expanded its outreach efforts to create an educational pathway for local high school and college students encouraging them to pursue higher education and health careers. A description of the Imi Ho'ola is presented with emphasis on its post-baccalaureate curriculum begun in 1995.

  2. Self-assembly behavior of β-cyclodextrin and imipramine. A Free energy perturbation study

    NASA Astrophysics Data System (ADS)

    Sun, Tingting; Shao, Xueguang; Cai, Wensheng

    2010-05-01

    The self-assembly behavior of β-cyclodextrin (β-CD) and imipramine (IMI), an antidepressant drug, was investigated by molecular dynamics simulations in the gas phase and in an aqueous solution. The binding free energies for 10 possible arrangements of β-CD/IMI complexes with stoichiometries of 1:1, 2:1, and 1:2 were determined using free energy perturbation calculations. The calculations suggest that the 2:1 inclusion mode is the most energetically favored in both phases, in good agreement with experiment. The environment and the neutral and charged IMI influence the stability of the aggregates. The electrostatic interactions constitute the main contribution to the stability. The results reported in this contribution shed new light on the mechanism of association of β-CD with IMI.

  3. Epidemiological and partial budget analysis for treatment of subclinical Staphylococcus aureus intramammary infections considering microbiological and cytological scenarios.

    PubMed

    Petzer, Inge-Marié; Etter, Eric M C; Donkin, Edward F; Webb, Edward C; Karzis, Joanne

    2017-12-01

    An innovative method was investigated to aid in the elimination of Staphylococcus aureus (S. aureus) intramammary infections (IMI) from dairy herds. A stochastic model explore the economic benefit of three-day or eight-day treatment of subclinical IMI in all S. aureus infected cows or in only those with a somatic cell count (SCC) exceeding 200,000 cells/ml. An epidemiological model was developed to run parallel to the economic model that would predict the S. aureus IMI likely to persist, develop new infections and clinical mastitis. In the economic model a first algorithm was used to consider the low prevalence (LP) scenario and made use of S. aureus prevalence information provided by retrospective analysis of microbiological and cytological results in South Africa (2008-2012). The data used considered Staphylococcus aureus prevalence from [1.495; 1.595] 95% to [6.72; 6.95] 95% for SCC≤200,000 and SCC>200,000 cells/ml respectively. A second algorithm considered the high prevalence (HP) scenario to evaluate a simulated situation with a 5[U1] [R12] to 25% prevalence. Scenarios of low or high transmission ratio (TR) were included in the model according to the hygiene management on the farm. Probabilities and costs were calculated over 255days. The economic models predicted average cost indices for low S. aureus IMI and low TR to vary from -3179 ZAR (South African Rands) when subclinical cases with SCC higher than 200,000 cell/ml were treated for eight days, to -3663 ZAR when all subclinical S. aureus IMI were treated for three days. With a HP and high TR of S. aureus the average cost indices changed from -18,042 ZAR when none to -5433 ZAR per 255days when all S. aureus IMI were treated for eight days. The epidemiological model in this study predicted substantial benefit of treatment mainly in high TR scenarios. New IMI decreased up to77% in the three-day and up to 91% in the eight-day treatment scenarios. In the HP scenarios, persistent IMI were reduced by 94%. The number of clinical cases predicted with no treatment for subclinical infections was higher than the total number of clinical and subclinical cases in scenarios where cows were treated three or eight days. Initial prudent treatment of subclinical IMI resulted in less overall treatments and less new, persistent and clinical cases. Combined results of economic and epidemiological models indicated that the option that cost the least did not always have the best epidemiological outcome. Models may assist in optimising and balancing decisions relating to financial and IMI. Copyright © 2017. Published by Elsevier B.V.

  4. Effect of application of an external teat sealant and/or oral treatment with a monensin capsule pre-calving on the prevalence and incidence of subclinical and clinical mastitis in dairy heifers.

    PubMed

    McDougall, S; Parker, K I; Weir, A M; Compton, C W R

    2008-06-01

    To assess the effect of applying an external teat sealant or a slow-release intraruminal monensin capsule pre-calving on the prevalence and incidence of subclinical or clinical mastitis in dairy heifers post-calving. The studies were undertaken in 13 herds. In two herds application of an external teat sealant was compared with a negative control; in nine herds treatment with monensin was compared with controls, and in two herds treatments were applied in a 2 x 2 factorial design. Heifers were randomly assigned within herd to be treated with a slow-release intraruminal device containing 32 g monensin (n=383), or left as untreated controls (n=389), approximately 30 days before the start of the spring calving period; or to be treated with a latex external teat sealant (n=206) when calving was impending, or be left as untreated controls (n=205). Milk samples were collected from each gland between 0 and 5 days after calving and from any gland diagnosed with clinical mastitis. The effect of the treatments on the prevalence of intramammary infection (IMI), i.e. subclinical mastitis, and clinical mastitis were initially analysed at the univariate level, with associated variables (p<0.2) being used in construction of multivariable models. The prevalence of IMI was 18.4% at the gland level, and coagulase-negative staphylococci followed by Streptococcus uberis were the most common isolates. Treatment with an external teat sealant reduced the prevalence, compared with controls, of any IMI (12.1 (SE 1.7)% vs 16.5 (SE 2.1)%, respectively; p=0.05) or IMI caused by a major pathogen (3.8 (SE 0.8)% vs 6.0 (SE 1.1)%, respectively; p=0.05). Monensin treatment did not affect the prevalence of any IMI (p=0.68) or IMI due to a major pathogen (p=0.11). The cumulative incidence of clinical mastitis was 14.2%. Neither monensin treatment (p=0.47) nor application of an external teat sealant (p=0.71) altered the risk of clinical mastitis. There was no interaction between the monensin and external teat sealant in the two herds where the treatments were applied in a 2 x 2 factorial design. Application of an external teat sealant resulted in a lower prevalence of any IMI and of an IMI caused by a major pathogen. Despite monensin reducing the mobilisation of body tissue and the risk of subclinical ketosis, it had no effect on the prevalence or incidence of IMI or clinical mastitis. Application of an external teat sealant is an option for reducing the prevalence of IMI in pasture fed dairy heifers.

  5. Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.

    PubMed

    Oberholzer, Inge; Möller, Marisa; Holland, Brendan; Dean, Olivia M; Berk, Michael; Harvey, Brian H

    2018-04-01

    There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.

  6. Infrastructure Management Information System User Manual

    DOT National Transportation Integrated Search

    1998-10-01

    This publication describes and explains the user interface for the Infrastructure Management Information System (IMIS). The IMIS is designed to answer questions regarding public water supply, wastewater treatment, and census information. This publica...

  7. Identification, typing, ecology and epidemiology of coagulase negative staphylococci associated with ruminants.

    PubMed

    Vanderhaeghen, Wannes; Piepers, Sofie; Leroy, Frédéric; Van Coillie, Els; Haesebrouck, Freddy; De Vliegher, Sarne

    2015-01-01

    Since phenotypic methods to identify coagulase negative staphylococci (CNS) from the milk of ruminants often yield unreliable results, methods for molecular identification based on gene sequencing or fingerprinting techniques have been developed. In addition to culture-based detection of isolates, culture-independent methods may be of interest. On the basis of molecular studies, the five CNS species commonly causing intramammary infections (IMI) are Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus simulans and Staphylococcus xylosus. Current knowledge suggests that S. chromogenes is a bovine-adapted species, with most cases of IMI due to this bacterium being opportunistic. S. haemolyticus also appears to be an opportunistic pathogen, but this bacterium occupies a variety of habitats, the importance of which as a source of IMI remains to be elucidated. S. xylosus appears to be a versatile species, but little is known of its epidemiology. S. epidermidis is considered to be a human-adapted species and most cases of IMI appear to arise from human sources, but the organism is capable of residing in other habitats. S. simulans typically causes contagious IMI, but opportunistic cases also occur and the ecology of this bacterium requires further study. Further studies of the ecology and epidemiology of CNS as a cause of IMI in cattle are required, along with careful attention to classification of these bacteria and the diseases they cause. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

    PubMed

    Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

    2015-02-24

    Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  9. Central Neurotoxicity of Immunomodulatory Drugs in Multiple Myeloma

    PubMed Central

    Patel, Urmeel H.; Mir, Muhammad A.; Sivik, Jeffrey K.; Raheja, Divisha; Pandey, Manoj K.; Talamo, Giampaolo

    2015-01-01

    Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy. PMID:25852850

  10. The Innovative Medicines Initiative moves translational immunology forward.

    PubMed

    Goldman, Michel; Wittelsberger, Angela; De Magistris, Maria-Teresa

    2013-02-01

    The Innovative Medicines Initiative (IMI) was established in 2008 as a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations with the mission to promote the development of novel therapies through collaborative efforts based on the concept of pre-competitive research. Several consortia supported by IMI are dedicated to immuno-inflammatory disorders, immune-based biopharmaceuticals and vaccines. Herein, we present the key principles underlying IMI, briefly review the status of projects related to translational immunology, and present future topics of interest to immunologists.

  11. Meta-analysis of dry cow management for dairy cattle. Part 1. Protection against new intramammary infections.

    PubMed

    Halasa, T; Osterås, O; Hogeveen, H; van Werven, T; Nielen, M

    2009-07-01

    The objective of this study was to estimate the preventive effect of various dry cow management measures against quarter new intramammary infections (IMI) during the dry period up to 21 d postcalving. Moreover, the potential publication bias was assessed in the studies selected for this analysis. The intervention measures were blanket dry cow therapy (BDCT), selective dry cow therapy (SDCT), cloxacillin compared with other dry cow therapy products, and teat sealant. A meta-analysis relative risk (RR) was calculated per intervention and pathogen group when enough studies were available from the 33 selected studies. Results of the meta-analyses were examined using publication bias tests. Blanket dry cow therapy showed significant protection against new IMI caused by Streptococcus spp. [the pooled RR was 0.39 (0.30 to 0.51)] but no protection was observed against coliform new IMI [the pooled RR was 0.95 (0.81 to 1.10)]. After correction for publication bias, it became doubtful whether DCT is protective against new Staphylococcus spp. IMI. Cloxacillin showed similar protection against new quarter IMI compared with other DCT products [the pooled RR was 1.09 (0.94 to 1.25)]. Selective dry cow therapy showed higher protection against new IMI compared with no DCT [the pooled RR was 0.51 (0.30 to 0.86)]. However, BDCT showed more protection when compared with SDCT [the pooled RR was 0.55 (0.37 to 0.80)], but the inference about whether BDCT is superior to SDCT was dependent on whether the selection criteria for SDCT was at the cow or quarter level. Internal teat sealants showed significant protection against new IMI during the dry period [the pooled RR was 0.39 (0.18 to 0.82)]. Publication bias should be taken into account when attempts are made to review literature in a meta-analysis.

  12. Efficacy of Imiquimod-Based Transcutaneous Immunization Using a Nano-Dispersed Emulsion Gel Formulation

    PubMed Central

    Tenzer, Stefan; Schild, Hansjörg; Stevanovic, Stefan; Langguth, Peter; Radsak, Markus P.

    2014-01-01

    Background Transcutaneous immunization (TCI) approaches utilize skin associated lymphatic tissues to elicit specific immune responses. In this context, the imidazoquinoline derivative imiquimod formulated in Aldara applied onto intact skin together with a cytotoxic T lymphocyte (CTL) epitope induces potent CTL responses. However, the feasibility and efficacy of the commercial imiquimod formulation Aldara is limited by its physicochemical properties as well as its immunogenicity. Methodology/Principal Findings To overcome these obstacles, we developed an imiquimod-containing emulsion gel (IMI-Gel) and characterized it in comparison to Aldara for rheological properties and in vitro mouse skin permeation in a Franz diffusion cell system. Imiquimod was readily released from Aldara, while IMI-Gel showed markedly decreased drug release. Nevertheless, comparing vaccination potency of Aldara or IMI-Gel-based TCI in C57BL/6 mice against the model cytotoxic T-lymphocyte epitope SIINFEKL, we found that IMI-Gel was equally effective in terms of the frequency of peptide-specific T-cells and in vivo cytolytic activity. Importantly, transcutaneous delivery of IMI-Gel for vaccination was clearly superior to the subcutaneous or oral route of administration. Finally, IMI-Gel based TCI was at least equally effective compared to Aldara-based TCI in rejection of established SIINFEKL-expressing E.G7 tumors in a therapeutic setup indicated by enhanced tumor rejection and survival. Conclusion/Significance In summary, we developed a novel imiquimod formulation with feasible pharmaceutical properties and immunological efficacy that fosters the rational design of a next generation transcutaneous vaccination platform suitable for the treatment of cancer or persistent virus infections. PMID:25025233

  13. A comparative study on the effects of electron beam irradiation on imidacloprid-resistant and -susceptible Aphis gossypii (Hemiptera: Aphididae)

    NASA Astrophysics Data System (ADS)

    Yun, Seung-Hwan; Koo, Hyun-Na; Lee, Seon-Woo; Kim, Hyun Kyung; Kim, Yuri; Han, Bumsoo; Kim, Gil-Hah

    2015-07-01

    The melon and cotton aphid, Aphis gossypii, is a polyphagous insect pest. This study compared the development, reproduction, DNA damage, recovery, and gene expression in imidacloprid-resistant (IMI-R) and -susceptible (S) strains of A. gossypii by electron beam irradiation. When 1st instar nymphs were irradiated with 100 Gy, the fecundity (nymphs of F1 generation) of the resultant adults were completely inhibited. When adults were irradiated with 200 Gy, the number of total 1st instar nymphs produced per adult was 3.0±1.7 and 1.9±1.4 in the S and IMI-R strains, respectively, but adult development was completely suppressed. However, electron beam irradiation did not affect adult longevity in either the S or IMI-R strain. There was no statistically significant difference between the effect of irradiation on the S and IMI-R strains. Therefore, electron beam irradiation at 200 Gy could be used as a phytosanitary irradiation treatment for both S and IMI-R strains of A. gossypii. The DNA damage caused by electron beam irradiation was evaluated by an alkaline comet assay. Exposure to an electron beam (50 Gy) induced DNA damage that was repaired to a similar level as the untreated control group (0 Gy) over time. However, at more than 100 Gy, the DNA damage was not completely repaired. The expression of P450, HSP70, cuticle protein, and elongation factor genes were higher in the IMI-R strain than in the S strain.

  14. The effect of internal teat sealant products (Teatseal and Orbeseal) on intramammary infection, clinical mastitis, and somatic cell counts in lactating dairy cows: a meta-analysis.

    PubMed

    Rabiee, A R; Lean, I J

    2013-01-01

    The objective of this study was to assess the efficacy of internal teat sealant products containing bismuth subnitrate (Teatseal and Orbeseal; Pfizer Animal Health, West Ryde, Australia) when used alone, or in the presence of antibiotic dry cow therapy (ADCT), before or at drying off on the incidence of new intramammary infections (IMI), clinical mastitis, and milk somatic cell count (SCC) during lactation. The literature search identified 18 English-language publications on the use of Teatseal in dairy cattle. A total of 12 studies with 17 subtrials or comparisons including 13 positive control subtrials (internal teat sealant and ADCT vs. ADCT) and 4 negative control subtrials (internal teat sealant vs. untreated) examining IMI were included in the analysis. Internal teat sealants, alone or in the presence of ADCT, reduced the risk of acquiring new IMI after calving by 25% [risk ratio (RR)=0.75; 95% confidence interval (CI): 0.67 to 0.83]. Internal teat sealants reduced the risk of IMI by 73% compared with untreated cows (RR=0.27; 95% CI: 0.13 to 0.55). The results of both meta-analyses of IMI, with positive and negative controls, were heterogeneous [I(2) (a statistic that describes the proportion of total variation in study effect estimates that is due to heterogeneity)=65.4 and 92.1%]. No farm or cow factors studied significantly contributed to the heterogeneity of the results. A total of 16 studies (21 subtrials), including 14 positive control subtrials and 7 negative control subtrials, examining clinical mastitis were included in the analysis. Internal teat sealants alone and in the presence of ADCT reduced the risk of clinical mastitis after calving in lactating cows by 29% (RR=0.71; 95% CI: 0.62 to 0.82), and 48% (RR=0.52; 95% CI: 0.37 to 0.75), respectively. The results of the meta-analysis on clinical mastitis with positive controls were homogeneous (I(2)=33.6%), whereas the results of studies with negative controls were heterogeneous (I(2)=60.4%). No farm or cow factors studied that had sufficient data to evaluate significantly contributed to the heterogeneity of the results. The estimated linear score (LS) of milk SCC after calving in published studies (n=3) and for studies that provided raw data (n=2), was significantly lower for cattle treated with internal teat sealants and ADCT in 3 studies than for cattle treated with internal teat sealants only. The estimated LS of pooled raw data of 3 studies from 32 herds showed that the LS of cows treated with internal teat sealant and ADCT was not significantly different than those treated with ADCT only. This study found that the application of internal teat sealants in the presence of ADCT or the use of internal teat sealants alone at dry off significantly reduced the incidence of IMI and clinical mastitis in lactating dairy cows compared with respective control groups. Further studies are needed to investigate the effect of internal teat sealants on postpartum milk SCC in lactating dairy cows. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. ITO/metal/ITO anode for efficient transparent white organic light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Joo, Chul Woong; Lee, Jonghee; Sung, Woo Jin; Moon, Jaehyun; Cho, Nam Sung; Chu, Hye Yong; Lee, Jeong-Ik

    2015-02-01

    We report on the characteristics of enhanced and balanced white-light emission of transparent organic light emitting diodes (TOLEDs) by introducing anode that has a stack structure of ITO/metal/ITO (IMI). We have investigated an anode that has a stack structure of IMI. IMI anodes are typically composed of a thin Ag layer (˜15 nm) sandwiched between two ITO layers (˜50 nm). By inserting an Ag layer it was possible to achieve sheet resistance lower than 3 Ω/sq. and transmittance of 86% at a wavelength of 550 nm. The Ag insert can act as a reflective component. With its counterpart, a transparent cathode made of a thin Ag layer (˜15 nm), micro-cavities (MC) can be effectively induced in the OLED, leading to improved performance. Using an IMI anode, it was possible to significantly increase the current efficiencies. The current efficiencies of the top and the bottom of the IMI TOLED increased to 23.0 and 15.6 cd/A, respectively, while those of the white TOLED with the ITO anode were 20.7 and 5.1 cd/A, respectively. A 30% enhancement in the overall current efficiency was achieved by taking advantage of the MC effect and the low sheet resistance.

  16. Prevalence of coagulase-positive staphylococci, other than Staphylococcus aureus, in bovine mastitis.

    PubMed

    Roberson, J R; Fox, L K; Hancock, D D; Gay, J M; Besser, T E

    1996-01-01

    To determine prevalence and relevance of coagulase-positive Staphylococcus hyicus and S intermedius intramammary infections (IMI) in dairy cows and determine the ability of the 4-hour tube coagulase (TC) test to differentiate the coagulase-positive staphylococci (CPS). Prevalence of CPS was determined for primiparous cows (point prevalence and prevalence at first parturition) and multiparous cows (point prevalence) of 2 herd groups: < 6% CPS IMI prevalence = low prevalence (LP); > 10% CPS IMI prevalence = high prevalence (HP). For prevalence, cows of 22 dairy herds. For TC, 1,038 CPS strains isolated from cow milk. Speciation of CPS from aseptically collected composite milk samples was performed. Coagulase-positive isolates from 4 cow groups were tested for their ability to coagulate rabbit plasma by 4 hours: LP and HP primiparous cows at parturition, and LP and HP cows any time after first parturition. Of 487 CPS in the prevalence study, 82.1% were S aureus, 17.7% were coagulase-positive S hyicus, and 0.2% were S intermedius. Of all CPS IMI in LP herds, 34% were coagulase-positive S hyicus; of all CPS IMI in HP herds, 9% were coagulase-positive S hyicus. Coagulase-positive S hyicus appeared to persist to the end of lactation in 4 cows (mean linear somatic cell count = 3.7). The TC test was > or = 97% sensitive, < or = 33% specific, and had a predictive value positive range of 60 to 97% for S aureus isolates. Coagulase-positive S hyicus appears capable of inducing chronic, low-grade IMI. Staphylococcus intermedius does not appear to be an important mastitis pathogen. The TC test is not valid to use as the sole method to differentiate CPS species.

  17. Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice.

    PubMed

    Bhaskar, Rakesh; Mohanty, Banalata

    2014-09-01

    Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Short communication: Species group-specific predictors at the cow and quarter level for intramammary infection with coagulase-negative staphylococci in dairy cattle throughout lactation.

    PubMed

    De Visscher, A; Piepers, S; Supré, K; Haesebrouck, F; De Vliegher, S

    2015-08-01

    Coagulase-negative staphylococci (CNS) are frequently isolated from quarters with subclinical mastitis, teat apices, and the cows' environment. Virulence, ecology, epidemiological behavior, and effect on udder health vary between different CNS species. Staphylococcus chromogenes, Staph. simulans, and Staph. xylosus are frequently present in milk and have a more substantial effect on quarter milk somatic cell count than other species. Therefore, these species are considered the "more relevant" CNS. As species-specific factors associated with CNS intramammary infection (IMI) have not yet been identified and susceptibility for IMI differs between cows and quarters, this study aimed to identify predictors for CNS IMI at the cow and quarter level (some of them changing over time) with a specific focus on the aforementioned more relevant CNS. Precise data were available from a longitudinal study (3,052 observations from 344 quarters from 86 dairy cows belonging to 3 commercial dairy herds). All CNS were molecularly identified to the species level, and multivariable, multilevel logistic regression models taking into account the longitudinal nature of the data, were fit to study the likelihood of infection. Staphylococcus chromogenes, Staph. xylosus, and Staph. cohnii were the most frequently isolated species from CNS IMI in older cows, whereas Staph. chromogenes, Staph. xylosus, and Staph. simulans were the main species found in IMI in heifers. Quarters from heifers (as opposed to multiparous cows), from heifers and multiparous cows in third or fourth month in lactation (as opposed to early lactation, <60 d in milk), and with an increasing quarter milk SCC were more likely to be infected with the more relevant CNS species. Quarter milk SCC was identified as the sole statistically significant predictor for IMI with other CNS species, although the size of the effect was lower [odds ratio of 1.6 (1.4-1.9) vs. 2.1 (1.8-2.5)] than the effect for IMI with the more relevant CNS. As a strong herd effect was present, studying herd-level predictors is warranted. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Immune response of Staphylococcus aureus strains in a mouse mastitis model is linked to adaptive capacity and genotypic profiles.

    PubMed

    Pereyra, Elizabet A L; Sacco, Sofía C; Duré, Andrea; Baravalle, Celina; Renna, María S; Andreotti, Carolina S; Monecke, Stefan; Calvinho, Luis F; Dallard, Bibiana E

    2017-05-01

    Staphylococcus aureus is one of the most frequently isolated major pathogens from intramammary infections (IMI) worldwide. The mechanisms by which S. aureus IMI are established and maintained in dairy cows involve both bacterial escape strategies and modulation of the host immune response. Moreover, it was shown that different S. aureus strains have varying effects on the immune response. The aim of this study was to investigate the immune response in a mouse mastitis model of two S. aureus strains isolated from bovine IMI with different clinical manifestation (persistent-P or non-persistent-NP), phenotypic and genotypic profile. Both strains were capable of establishing an IMI after 264h post inoculation (pi). Strain A (NP) showed a more aggressive behaviour than strain B (P) at early stages of IMI, while strain B multiplied initially at a lower rate but increased its replication capacity from 120h pi to the end of the study (264h pi). Strain A triggered a stronger initial inflammatory response compared with strain B inducing higher gene and protein expression of TLR2, NF-κB activation and higher gene expression of IL-1α at initial stage of IMI (6-12h pi) but inducing extensive mammary tissue damage. Immune cells response was different for each S. aureus strain throughout the course of infection, showing mammary glands inoculated with strain A greater initial immune cells stimulation compared with strain B and then a second immune cells stimulation (from 120 to 264h pi) represented by monocytes-macrophages, T and B lymphocytes, mainly stimulated by strain B, consistent with inflammatory process becoming chronic. Strain-specific pathogenicity observed underscores the importance of pathogen factors in the progression of the infectious process. These results contribute to increase the available information on host-pathogen interaction and point out for the need of further research to expand the knowledge about these interactions for developing new strategies to intervene in the IMI progress. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Associations of udder-health indicators with cow factors and with intramammary infection in dairy cows.

    PubMed

    Nyman, A-K; Persson Waller, K; Bennedsgaard, T W; Larsen, T; Emanuelson, U

    2014-09-01

    The objective of this study was to investigate if and how cow factors and intramammary infection (IMI) are associated with 4 different udder-health indicators in dairy cows as a first step in investigating whether the diagnostic performance of these indicators can be improved. The investigated indicators were somatic cell count (SCC), lactate dehydrogenase (LDH), N-acetyl-β-d-glucosaminidase (NAGase), and alkaline phosphatase (AP) measured in milk. In this cross-sectional study, approximately 1,000 cows from 25 dairy herds were sampled for bacteriology (quarter milk samples) during 3 consecutive days: the day before test milking, at the day of test milking, and at the day after test milking. The whole-udder test milking sample was analyzed for milk composition, SCC, LDH, NAGase, and AP. Cow data (parity, breed, milk yield, percentage of milk fat and protein, milk urea concentration, and days in milk from the sampled test milking) were collected from the Swedish milk-recording scheme. Of the sampled cows 485 were considered IMI negative and were used in multivariable mixed-effect linear regression models to investigate associations between cow factors and the udder-health indicators. A second modeling including all cows, both IMI negative and IMI positive (256 cows), was also performed. The results showed that all udder-health indicators were affected by cow factors but that different cow factors were associated with different indicators. Intramammary-infection status was significantly associated with all udder-health indicators except AP. Parity and milk urea concentration were the only cow factors associated with all indicators in all models. The significant cow factors explained 23% of the variation in SCC and >30% of the variation in LDH, NAGase, and AP in IMI-negative cows, showing that LDH, NAGase, and AP are more affected than SCC by cow factors. The IMI status explained 23% of the variation in SCC in the model with all cows but only 7% of the variation in LDH and 2% of the variation in NAGase, indicating that SCC has the best potential as a diagnostic tool in finding cows with IMI. However, further studies are needed to investigate whether the diagnostic properties of these udder-health indicators will improve with adjustment according to their associations with different cow factors when used as a diagnostic tool for finding cows with IMI. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Development of Intensive Motivational Interviewing (IMI) and Modifications for Treating Women with Alcohol Use Disorders.

    PubMed

    Polcin, Douglas L; Korcha, Rachael; Nayak, Madhabika

    2018-06-01

    Women have greater vulnerability to alcohol problems than men. They become intoxicated after drinking half as much as men, develop cirrhosis of the liver more rapidly, and have a greater risk of dying from alcohol-related accidents. Despite more serious consequences related to their drinking, treatment for women with alcohol use disorders has been understudied relative to treatment for men. Intensive motivational interviewing (IMI) is a recent psychotherapeutic intervention for substance abuse problems that draws on the principles of brief motivational interviewing (1-2 session). However, the intervention includes 9 sessions designed to enable therapists to have maximum flexibility to facilitate factors known to be important for women with substance use disorders, such as active facilitation of client-therapist collaboration, empowerment, and affirmation of strengths. This paper reviews the development of IMI, initial favorable findings for women with co-occurring methamphetamine and alcohol problems, and the design of an ongoing longitudinal study assessing the effects of MI for women with alcohol problems over a 12-month time period. Relational Theory is used as a conceptual framework for understanding IMI for women. The theory emphasizes understanding, building, and modifying interpersonal relationships as a central goal. From this perspective, self-efficacy, self-esteem, and reduction in drinking are enhanced through interpersonal connections with others. Plans for additional study of IMI are described along with suggestions for therapists.

  2. Integrating Sequence-based GWAS and RNA-Seq Provides Novel Insights into the Genetic Basis of Mastitis and Milk Production in Dairy Cattle

    PubMed Central

    Fang, Lingzhao; Sahana, Goutam; Su, Guosheng; Yu, Ying; Zhang, Shengli; Lund, Mogens Sandø; Sørensen, Peter

    2017-01-01

    Connecting genome-wide association study (GWAS) to biological mechanisms underlying complex traits is a major challenge. Mastitis resistance and milk production are complex traits of economic importance in the dairy sector and are associated with intra-mammary infection (IMI). Here, we integrated IMI-relevant RNA-Seq data from Holstein cattle and sequence-based GWAS data from three dairy cattle breeds (i.e., Holstein, Nordic red cattle, and Jersey) to explore the genetic basis of mastitis resistance and milk production using post-GWAS analyses and a genomic feature linear mixed model. At 24 h post-IMI, genes responsive to IMI in the mammary gland were preferentially enriched for genetic variants associated with mastitis resistance rather than milk production. Response genes in the liver were mainly enriched for variants associated with mastitis resistance at an early time point (3 h) post-IMI, whereas responsive genes at later stages were enriched for associated variants with milk production. The up- and down-regulated genes were enriched for associated variants with mastitis resistance and milk production, respectively. The patterns were consistent across breeds, indicating that different breeds shared similarities in the genetic basis of these traits. Our approaches provide a framework for integrating multiple layers of data to understand the genetic architecture underlying complex traits. PMID:28358110

  3. Profiling characteristics of internet medical information users.

    PubMed

    Weaver, James B; Mays, Darren; Lindner, Gregg; Eroglu, Dogan; Fridinger, Frederick; Bernhardt, Jay M

    2009-01-01

    The Internet's potential to bolster health promotion and disease prevention efforts has attracted considerable attention. Existing research leaves two things unclear, however: the prevalence of online health and medical information seeking and the distinguishing characteristics of individuals who seek that information. This study seeks to clarify and extend the knowledge base concerning health and medical information use online by profiling adults using Internet medical information (IMI). Secondary analysis of survey data from a large sample (n = 6,119) representative of the Atlanta, GA, area informed this investigation. Five survey questions were used to assess IMI use and general computer and Internet use during the 30 days before the survey was administered. Five questions were also used to assess respondents' health care system use. Several demographic characteristics were measured. RESULTS Contrary to most prior research, this study found relatively low prevalence of IMI-seeking behavior. Specifically, IMI use was reported by 13.2% of all respondents (n = 6,119) and by 21.1% of respondents with Internet access (n = 3,829). Logistic regression models conducted among respondents accessing the Internet in the previous 30 days revealed that, when controlling for several sociodemographic characteristics, home computer ownership, online time per week, and health care system use are all positively linked with IMI-seeking behavior. The data suggest it may be premature to embrace unilaterally the Internet as an effective asset for health promotion and disease prevention efforts that target the public.

  4. Reliability and Validity of a Scale for Rating Memory Impairment in Hospitalized Amnesiacs.

    ERIC Educational Resources Information Center

    Knight, Robert G.; Godfrey, Hamish P. D.

    1984-01-01

    Investigated the reliability and concurrent validity of the Inpatient Memory Impairment Scale (IMIS), using a group of memory-impaired chronic alcoholic and Korsakoff patients (N=20). Analysis revealed that the IMIS had a high degree of internal consistency and that interrater reliability is also high. (LLL)

  5. Severe Speech Sound Disorders: An Integrated Multimodal Intervention

    ERIC Educational Resources Information Center

    King, Amie M.; Hengst, Julie A.; DeThorne, Laura S.

    2013-01-01

    Purpose: This study introduces an integrated multimodal intervention (IMI) and examines its effectiveness for the treatment of persistent and severe speech sound disorders (SSD) in young children. The IMI is an activity-based intervention that focuses simultaneously on increasing the "quantity" of a child's meaningful productions of target words…

  6. IMIS: Integrated Maintenance Information System. A maintenance information delivery concept

    NASA Technical Reports Server (NTRS)

    Vonholle, Joseph C.

    1987-01-01

    The Integrated Maintenance Information System (IMIS) will optimize the use of available manpower, enhance technical performance, improve training, and reduce the support equipment and documentation needed for deployment. It will serve as the technician's single, integrated source of all the technical information required to perform modern aircraft maintenance.

  7. WAIS-III FSIQ and GAI in ability-memory discrepancy analysis.

    PubMed

    Glass, Laura A; Bartels, Jared M; Ryan, Joseph J

    2009-01-01

    The present investigation compares WAIS-III FSIQ-WMS-III with GAI-WMS-III discrepancies in 135 male inpatients with suspected memory impairment. Full Scale IQ and GAI scores were highly correlated, r= .96, with mean values of 92.10 and 93.59, respectively. Additional analyses with the ability composites compared to each WMS-III index (IMI, GMI, and DMI), the GAI consistently produced larger difference scores than did the FSIQ; however, effect sizes were relatively small (ES= .12). Lastly, case-by-case analyses demonstrated concordance rates of 86% for the FSIQ-IMI and GAI-IMI comparisons, 85% for the FSIQ-GMI and GAI-GMI, and 82% for the FSIQ-DMI and GAI-DMI.

  8. Trends in OSHA Compliance Monitoring Data 1979-2011: Statistical Modeling of Ancillary Information across 77 Chemicals.

    PubMed

    Sarazin, Philippe; Burstyn, Igor; Kincl, Laurel; Lavoué, Jérôme

    2016-05-01

    The Integrated Management Information System (IMIS) is the largest multi-industry source of exposure measurements available in North America. However, many have suspected that the criteria through which worksites are selected for inspection are related to exposure levels. We investigated associations between exposure levels and ancillary variables in IMIS in order to understand the predictors of high exposure within an enforcement context. We analyzed the association between nine variables (reason for inspection, establishment size, total amount of penalty, Occupational Safety and Health Administration (OSHA) plan, OSHA region, union status, inspection scope, year, and industry) and exposure levels in IMIS using multimodel inference for 77 agents. For each agent, we used two different types of models: (i) logistic models were used for the odds ratio (OR) of exposure being above the threshold limit value (TLV) and (ii) linear models were used for exposure concentrations restricted to detected results to estimate percent increase in exposure level, i.e. relative index of exposure (RIE). Meta-analytic methods were used to combine results for each variable across agents. A total of 511,047 exposure measurements were modeled for logistic models and 299,791 for linear models. Higher exposures were measured during follow-up inspections than planned inspections [meta-OR = 1.61, 95% confidence interval (CI): 1.44-1.81; meta-RIE = 1.06, 95% CI: 1.03-1.09]. Lower exposures were observed for measurements collected under state OSHA plans compared to measurements collected under federal OSHA (meta-OR = 0.82, 95% CI: 0.73-0.92; meta-RIE = 0.86, 95% CI: 0.81-0.91). A 'high' total historical amount of penalty relative to none was associated with higher exposures (meta-OR = 1.54, 95% CI: 1.40-1.71; meta-RIE = 1.18, 95% CI: 1.13-1.23). The relationships observed between exposure levels and ancillary variables across a vast majority of agents suggest that certain elements of OSHA's process of selecting worksites for inspection influence the exposure levels that OSHA inspectors encounter. Nonetheless, given the paucity of other sources of exposure data and the lack of a more demonstrably representative data source, our study considers the use of IMIS data for the estimation of exposures in the broader universe of worksites in the USA. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  9. 78 FR 39773 - Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... Eligibility To Apply for Worker Adjustment Assistance TA-W-82,678 Cannon Equipment, Carts Department, A Subsidiary of IMI Americas, Inc., Including On-Site Leased Workers From Aerotek And The Work Connection, Rosemount, Minnesota TA-W-82,678A Cannon Equipment, A Subsidiary of IMI Americas, Inc., Including On-Site...

  10. Different components of /sup 3/H-imipramine binding in rat brain membranes: relation to serotonin uptake sites

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gobbi, M.; Taddei, C.; Mennini, T.

    1988-01-01

    In the present paper, the authors confirm and extend previous studies showing heterogeneous /sup 3/H-imipramine (/sup 3/H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM /sup 3/H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three /sup 3/H-IMI binding sites: two of these were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a close relation to serontoninmore » uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific /sup 3/H-IMI, may be of help in understanding its relation with serotonin uptake system. 22 references, 2 figures, 2 tables.« less

  11. Enzymes and Inhibitors in Neonicotinoid Insecticide Metabolism

    PubMed Central

    Shi, Xueyan; Dick, Ryan A.; Ford, Kevin A.; Casida, John E.

    2009-01-01

    Neonicotinoid insecticide metabolism involves considerable substrate specificity and regioselectivity of the relevant CYP450, aldehyde oxidase, and phase II enzymes. Human CYP450 recombinant enzymes carry out the following conversions: CYP3A4, 2C19 and 2B6 for thiamethoxam (TMX) to clothianidin (CLO); 3A4, 2C19 and 2A6 for CLO to desmethyl-CLO; 2C19 for TMX to desmethyl-TMX. Human liver aldehyde oxidase reduces the nitro substituent of CLO to nitroso much more rapidly than that of TMX. Imidacloprid (IMI), CLO and several of their metabolites do not give detectable N-glucuronides but 5-hydroxy-IMI, 4,5-diol-IMI and 4-hydroxy-thiacloprid are converted to O-glucuronides in vitro with mouse liver microsomes and UDP-glucuronic acid or in vivo in mice. Mouse liver cytosol with S-adenosylmethionine converts desmethyl-CLO to CLO but not desmethyl-TMX to TMX. Two organophosphorus CYP450 inhibitors partially block IMI, thiacloprid and CLO metabolism in vivo in mice, elevating the brain and liver levels of the parent compounds while reducing amounts of the hydroxylated metabolites. PMID:19391582

  12. Immunomodulatory drugs in multiple myeloma: mechanisms of action and clinical experience

    PubMed Central

    Holstein, Sarah A.; McCarthy, Philip L.

    2017-01-01

    Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis. PMID:28205024

  13. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide

    PubMed Central

    Fischer, Eric S.; Böhm, Kerstin; Lydeard, John R.; Yang, Haidi; Stadler, Michael B.; Cavadini, Simone; Nagel, Jane; Serluca, Fabrizio; Acker, Vincent; Lingaraju, Gondichatnahalli M.; Tichkule, Ritesh B.; Schebesta, Michael; Forrester, William C.; Schirle, Markus; Hassiepen, Ulrich; Ottl, Johannes; Hild, Marc; Beckwith, Rohan E. J.; Harper, J. Wade; Jenkins, Jeremy L.; Thomä, Nicolas H.

    2015-01-01

    In the 1950s the drug thalidomide administered as a sedative to pregnant women led to the birth of thousands of children with multiple defects. Despite its teratogenicity, thalidomide and its derivatives lenalidomide and pomalidomide (together known as Immunomodulatory Drugs: IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-dysplasia. IMiDs target the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase and promote the ubiquitination of Ikaros/Aiolos transcription factors by CRL4CRBN. Here we present the crystal structure of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide. The structure establishes CRBN as a CRL4CRBN substrate receptor, which enantioselectively binds IMiDs. Through an unbiased screen we identify the homeobox transcription factor MEIS2 as an endogenous substrate of CRL4CRBN. Our studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4CRBN when recruiting Ikaros/Aiolos for degradation. This dual activity implies that small molecules can principally modulate a ligase to up- or down-regulate the ubiquitination of proteins. PMID:25043012

  14. Down-regulation of sup 3 H-imipramine binding sites in rat cerebral cortex prenatal exposure to antidepressants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montero, D.; de Ceballos, M.L.; Del Rio, J.

    1990-01-01

    Several antidepressant drugs were given to pregnant rats in the last 15 days of gestation and {sup 3}H-imipramine binding ({sup 3}H-IMI) was subsequently measured in the cerebral cortex of the offspring. The selective serotonin (5-HT) uptake blockers chlorimipramine and fluoxetine as well as the selective monoamine oxidase (MAO) inhibitors clorgyline and deprenyl induced, after prenatal exposure, a down-regulation of {sup 3}H-IMI binding sites at postnatal day 25. The density of these binding sites was still reduced at postnatal day 90 in rats exposed in utero to the MAO inhibitors. The antidepressants desipramine and nomifensine were ineffective in this respect. Aftermore » chronic treatment of adult animals, only chlorimipramine was able to down-regulate the {sup 3}H-IMI binding sites. Consequently, prenatal exposure of rats to different antidepressant drugs affecting predominantly the 5-HT systems induces more marked and long-lasting effects on cortical {sup 3}H-IMI binding sites. The results suggest that the developing brain is more susceptible to the actions of antidepressants.« less

  15. Use of a staphylococcal vaccine to reduce prevalence of mastitis and lower somatic cell counts in a registered Saanen dairy goat herd.

    PubMed

    Kautz, F M; Nickerson, S C; Ely, L O

    2014-08-01

    This investigation evaluated the efficacy of a bacterin in reducing the prevalence of staphylococcal mastitis and somatic cell counts (SCC) in a dairy goat herd. Does were vaccinated or left as controls, and the levels of mastitis and SCC monitored over 18 months. Staphylococcus caprae (42.5%), S. xylosus (15.1%), and S. simulans (10.0%) were the predominant causes of intramammary infections (IMI). The infection rate was 1.64 IMI/doe among vaccinates, which tended to be lower (P < 0.12) than controls (2.67 IMI/doe). The spontaneous cure rate of IMI after immunization was 1.28 cures/doe in vaccinates, which was higher than controls (0.6 cures/doe; P < 0.043). Average SCC of milk samples from vaccinates tended to be lower than that of controls (1274 × 10(3)/ml vs. 1529 × 10(3)/ml, respectively) (P < 0.10). Results support the continued study of mastitis vaccines for use in managing staphylococcal mastitis and SCC in dairy goats. Published by Elsevier Ltd.

  16. Imidacloprid insecticide exposure induces stress and disrupts glucose homeostasis in male rats.

    PubMed

    Khalil, Samah R; Awad, Ashraf; Mohammed, Hesham H; Nassan, Mohamed Abdo

    2017-10-01

    In the present study, we evaluated the stress response in adult rats who were administered imidacloprid (IMI) orally in two doses (0.5 and 1.0mg/kg bw for 60days). It led to an alteration in the levels of cortisone and catecholamines and induced behavioral deficits, particularly in the animals exposed to the dose of 1.0mg/kg. IMI was further analyzed for the effect on glucose homeostasis in developing and adult rats at a dose of 1.0mg/kg bw where it elicited a hyperglycemic effect. Moreover, we observed an alteration in the mRNA levels of glucose transporters. Histopathological and immunohistochemical data displayed structural perturbations in pancreatic tissue with a decline in the expression of insulin and GLUT4, particularly in the developing rats. Collectively, IMI treatment resulted in stress represented by behavioral and biochemical changes, particularly at a dose of 1.0mg/kg bw. Moreover, IMI perturbed the glucose regulation through hyperglycemic activity in both developing and adult rats, an observation clearly evident in the developing rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Profiling Characteristics of Internet Medical Information Users

    PubMed Central

    Weaver, James B.; Mays, Darren; Lindner, Gregg; Eroğlu, Doğan; Fridinger, Frederick; Bernhardt, Jay M.

    2009-01-01

    Objective The Internet's potential to bolster health promotion and disease prevention efforts has attracted considerable attention. Existing research leaves two things unclear, however: the prevalence of online health and medical information seeking and the distinguishing characteristics of individuals who seek that information. Design This study seeks to clarify and extend the knowledge base concerning health and medical information use online by profiling adults using Internet medical information (IMI). Secondary analysis of survey data from a large sample (n = 6,119) representative of the Atlanta, GA, area informed this investigation. Measurements Five survey questions were used to assess IMI use and general computer and Internet use during the 30 days before the survey was administered. Five questions were also used to assess respondents' health care system use. Several demographic characteristics were measured. Results Contrary to most prior research, this study found relatively low prevalence of IMI-seeking behavior. Specifically, IMI use was reported by 13.2% of all respondents (n = 6,119) and by 21.1% of respondents with Internet access (n = 3,829). Logistic regression models conducted among respondents accessing the Internet in the previous 30 days revealed that, when controlling for several sociodemographic characteristics, home computer ownership, online time per week, and health care system use are all positively linked with IMI-seeking behavior. Conclusions The data suggest it may be premature to embrace unilaterally the Internet as an effective asset for health promotion and disease prevention efforts that target the public. PMID:19567794

  18. Neonicotinoid Binding, Toxicity and Expression of Nicotinic Acetylcholine Receptor Subunits in the Aphid Acyrthosiphon pisum

    PubMed Central

    Taillebois, Emiliane; Beloula, Abdelhamid; Quinchard, Sophie; Jaubert-Possamai, Stéphanie; Daguin, Antoine; Servent, Denis; Tagu, Denis

    2014-01-01

    Neonicotinoid insecticides act on nicotinic acetylcholine receptor and are particularly effective against sucking pests. They are widely used in crops protection to fight against aphids, which cause severe damage. In the present study we evaluated the susceptibility of the pea aphid Acyrthosiphon pisum to the commonly used neonicotinoid insecticides imidacloprid (IMI), thiamethoxam (TMX) and clothianidin (CLT). Binding studies on aphid membrane preparations revealed the existence of high and low-affinity binding sites for [3H]-IMI (Kd of 0.16±0.04 nM and 41.7±5.9 nM) and for the nicotinic antagonist [125I]-α-bungarotoxin (Kd of 0.008±0.002 nM and 1.135±0.213 nM). Competitive binding experiments demonstrated that TMX displayed a higher affinity than IMI for [125I]-α-bungarotoxin binding sites while CLT affinity was similar for both [125I]-α-bungarotoxin and [3H]-IMI binding sites. Interestingly, toxicological studies revealed that at 48 h, IMI (LC50 = 0.038 µg/ml) and TMX (LC50 = 0.034 µg/ml) were more toxic than CLT (LC50 = 0.118 µg/ml). The effect of TMX could be associated to its metabolite CLT as demonstrated by HPLC/MS analysis. In addition, we found that aphid larvae treated either with IMI, TMX or CLT showed a strong variation of nAChR subunit expression. Using semi-quantitative PCR experiments, we detected for all insecticides an increase of Apisumα10 and Apisumβ1 expressions levels, whereas Apisumβ2 expression decreased. Moreover, some other receptor subunits seemed to be differently regulated according to the insecticide used. Finally, we also demonstrated that nAChR subunit expression differed during pea aphid development. Altogether these results highlight species specificity that should be taken into account in pest management strategies. PMID:24801634

  19. Neonicotinoids in the Canadian aquatic environment: a literature review on current use products with a focus on fate, exposure, and biological effects.

    PubMed

    Anderson, J C; Dubetz, C; Palace, V P

    2015-02-01

    Developed to replace organophosphate and carbamate insecticides, neonicotinoids are structurally similar to nicotine. The three main neonicotinoid insecticides, imidacloprid, clothianidin, and thiamethoxam, are being re-evaluated by Health Canada's Pest Management Regulatory Agency (PMRA). An important aspect of the re-evaluation is the potential for effects in non-target organisms, including aquatic organisms. Leaching into surface waters is one of the major concerns surrounding extensive use of neonicotinoids, especially in close proximity to water bodies. The PMRA has classified IMI as 'persistent' with a 'high' leaching potential. Globally, neonicotinoids have been detected in a variety of water bodies, typically at concentrations in the low μg/L range. While IMI has been included in some monitoring exercises, there are currently very few published data for the presence of CLO and THM in Canadian water bodies. The majority of neonicotinoid toxicity studies have been conducted with IMI due to its longer presence on the market and high prevalence of use. Aquatic insects are particularly vulnerable to neonicotinoids and chronic toxicity has been observed at concentrations of IMI below 1 μg/L. Acute toxicity has been reported at concentrations below 20 μg/L for the most sensitive species, including Hyalella azteca, ostracods, and Chironomus riparius. Fish, algae, amphibians, and molluscs are relatively insensitive to IMI. However, the biological effects of THM and CLO have not been as well explored. The Canadian interim water quality guideline for IMI is 0.23 μg/L, but there is currently insufficient use, fate, and toxicological information available to establish guidelines for CLO and THM. Based on concentrations of neonicotinoids reported in surface waters in Canada and globally, there is potential for aquatic invertebrates to be negatively impacted by neonicotinoids. Therefore, it is necessary to address knowledge gaps to inform decisions around guidelines and registration status for neonicotinoid insecticides in Canada to protect our aquatic ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Invited review: effect, persistence, and virulence of coagulase-negative Staphylococcus species associated with ruminant udder health.

    PubMed

    Vanderhaeghen, W; Piepers, S; Leroy, F; Van Coillie, E; Haesebrouck, F; De Vliegher, S

    2014-09-01

    The aim of this review is to assess the effect of coagulase-negative staphylococci (CNS) species on udder health and milk yield in ruminants, and to evaluate the capacity of CNS to cause persistent intramammary infections (IMI). Furthermore, the literature on factors suspected of playing a role in the pathogenicity of IMI-associated CNS, such as biofilm formation and the presence of various putative virulence genes, is discussed. The focus is on the 5 CNS species that have been most frequently identified as causing bovine IMI using reliable molecular identification methods (Staphylococcus chromogenes, Staphylococcus simulans, Staphylococcus haemolyticus, Staphylococcus xylosus, and Staphylococcus epidermidis). Although the effect on somatic cell count and milk production is accepted to be generally limited or nonexistent for CNS as a group, indications are that the typical effects differ between CNS species and perhaps even strains. It has also become clear that many CNS species can cause persistent IMI, contrary to what has long been believed. However, this trait appears to be quite complicated, being partly strain dependent and partly dependent on the host's immunity. Consistent definitions of persistence and more uniform methods for testing this phenomenon will benefit future research. The factors explaining the anticipated differences in pathogenic behavior appear to be more difficult to evaluate. Biofilm formation and the presence of various staphylococcal virulence factors do not seem to (directly) influence the effect of CNS on IMI but the available information is indirect or insufficient to draw consistent conclusions. Future studies on the effect, persistence, and virulence of the different CNS species associated with IMI would benefit from using larger and perhaps even shared strain collections and from adjusting study designs to a common framework, as the large variation currently existing therein is a major problem. Also within-species variation should be investigated. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Development of a new method for the determination of residues of the neonictinoid insecticide imidacloprid in juvenile Chinook (Oncorhynchus tyshawytscha) using ELISA detection

    USGS Publications Warehouse

    Frew, John A.; Grue, Christian E.

    2012-01-01

    The neonicotinoid insecticide imidacloprid (IMI) has been proposed as an alternative to carbaryl for controlling indigenous burrowing shrimp on commercial oyster beds in Willapa Bay and Grays Harbor, Washington. A focus of concern over the use of this insecticide in an aquatic environment is the potential for adverse effects from exposure to non-target species residing in the Bay, such as juvenile Chinook (Oncorhynchus tshawytscha) and cutthroat trout (O. clarki). Federal registration and State permiting approval for the use of IMI will require confirmation that the compound does not adversely impact these salmonids following field applications. This will necessitate an environmental monitoring program for evaluating exposure in salmonids following the treatment of beds. Quantification of IMI residues in tissue can be used for determining salmonid exposure to the insecticide. Refinement of an existing protocol using liquid-chromatography mass spectrometry (LC-MS) detection would provide the low limits of quantification, given the relatively small tissue sample sizes, necessary for determining exposure in individual fish. Such an approach would not be viable for the environmental monitoring effort in Willapa Bay and Grays Harbor due to the high costs associated with running multiple analyses, however. A new sample preparation protocol was developed for use with a commercially available enzyme-linked immunosorbent assay (ELISA) for the quantification of IMI, thereby providing a low-cost alternative to LC-MS for environmental monitoring in Willapa Bay and Grays Harbor. Extraction of the analyte from the salmonid brain tissue was achieved by Dounce homogenization in 4.0 mL of 20.0 mM Triton X-100, followed by a 6 h incubation at 50–55 °C. Centrifugal ultrafiltration and reversed phase solid phase extraction were used for sample cleanup. The limit of quantification for an average 77.0 mg whole brain sample was calculated at 18.2 μg kg-1 (ppb) with an average recovery of 79%. This relatively low limit of quantification allows for the analysis of individual fish. Using controlled laboratory studies, a curvelinear relationship was found between the measured IMI residue concentrations in brain tissue and exposure concentrations in seawater. Additonally, a range of IMI brain residue concentrations was associated with an overt effect; illustrating the utility of the IMI tissue residue quantification approach for linking exposure with defined effects.

  2. Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study.

    PubMed

    Ryan, Donna H; Johnson, William D; Myers, Valerie H; Prather, Tiffany L; McGlone, Meghan M; Rood, Jennifer; Brantley, Phillip J; Bray, George A; Gupta, Alok K; Broussard, Alan P; Barootes, Bryan G; Elkins, Brian L; Gaudin, David E; Savory, Robert L; Brock, Ricky D; Datz, Geralyn; Pothakamuri, Srininvasa R; McKnight, G Tipton; Stenlof, Kaj; Sjöström, Lars V

    2010-01-25

    Effective primary care practice (PCP) treatments are needed for extreme obesity. The Louisiana Obese Subjects Study (LOSS) tested whether, with brief training, PCPs could effectively implement weight loss for individuals with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 40 to 60. The LOSS, a 2-year (July 5, 2005, through January 30, 2008) randomized, controlled, "pragmatic clinical trial" trained 7 PCPs and 1 research clinic in obesity management. Primary outcome measure was year-2 percentage change from baseline weight. Volunteers (597) were screened and randomized to intensive medical intervention (IMI) (n = 200) or usual care condition (UCC) (n = 190). The UCC group had instruction in an Internet weight management program. The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy (sibutramine hydrochloride, orlistat, or diethylpropion hydrochloride) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24. The mean age of participants was 47 years; 83% were women, and 75% were white. Retention rates were 51% for the IMI group and 46% for the UCC group (P = .30). After 2 years, the results were as follows: (1) among 390 randomized participants, 31% in the IMI group achieved a 5% or more weight loss and 7% achieved a 20% weight loss or more, compared with 9% and 1% of those in the UCC group. (2) The mean +/- SEM baseline observation carried forward analysis showed a weight loss of -4.9% +/- 0.8% in IMI and -0.2 +/- 0.3% in UCC. (3) Last observation carried forward analysis showed a weight loss of -8.3% +/- 0.79% for IMI, whereas UCC was -0.0% +/- 0.4%. (4) A total of 101 IMI completers lost -9.7% +/- 1.3% (-12.7 +/- 1.7 kg), whereas 89 UCC completers lost -0.4% +/- 0.7% (-0.5 +/- 0.9 kg); (P < .001 for all group differences). Many metabolic parameters improved. Primary care practices can initiate effective medical management for extreme obesity; future efforts must target improving retention and weight loss maintenance. clinicaltrials.gov Identifier: NCT00115063.

  3. Short communication: Subtyping of Staphylococcus haemolyticus isolates from milk and corresponding teat apices to verify the potential teat-skin origin of intramammary infections in dairy cows.

    PubMed

    Leroy, Frédéric; Van Coillie, Els; Braem, Gorik; Piessens, Veerle; Verbist, Bert; De Vuyst, Luc; De Vliegher, Sarne

    2015-11-01

    Coagulase-negative staphylococci (CNS) are a major cause of intramammary infections (IMI) in dairy cows and they colonize the teat skin. Staphylococcus haemolyticus, one of the more common CNS, has been identified as a highly versatile opportunistic species. The aim of the present study was to gain better insight into the adaptation of S. haemolyticus subtypes to the udder ecosystem with respect to IMI development. During a longitudinal observational study conducted over 13 mo on 6 Flemish dairy herds, S. haemolyticus isolates were recovered from milk and teat apices. A total of 44 S. haemolyticus isolates originating from milk (24 isolates) and teat apices (20 isolates) of 6 selected udder quarters were singled out and analyzed using a combined methodology of (GTG)5-PCR and amplified fragment length polymorphism (AFLP) fingerprinting to determine intraspecies differences. Combining both fingerprinting methods, 4 S. haemolyticus subtypes were obtained (I to IV). Subtypes I, II, and IV were recovered from both milk and teat apex samples and were found to be associated with persisting IMI. Subtype III, not apparently related to IMI, was isolated solely from teat apices and not from milk. In general, S. haemolyticus subtypes found in milk from infected quarters could be recovered from the corresponding teat apices, although the latter could be colonized with up to 3 different subtypes. Comparing subtypes from milk and teat apices indicates that the IMI-causing agent likely originates from the teat skin. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Differential block of nicotinic synapses on B versus C neurones in sympathetic ganglia of frog by alpha-conotoxins MII and ImI.

    PubMed

    Tavazoie, S F; Tavazoie, M F; McIntosh, J M; Olivera, B M; Yoshikami, D

    1997-03-01

    1. The effects of two new acetylcholine receptor antagonists, alpha-conotoxin MII and alpha-conotoxin ImI, on nicotinic synaptic transmission in the 10th paravertebral sympathetic ganglion of the leopard frog (Rana pipiens) were examined. The preganglionic nerve was electrically stimulated (at low frequency, < or = 1 min-1, to avoid use-dependent changes) while compound action potentials of B and C neurones were monitored from the postganglionic nerve. 2. alpha-Conotoxins MII and ImI, at low micromolar concentrations, reversibly blocked both B and C waves, alpha-Conotoxin MII blocked the C wave more effectively than the B wave, whereas the potency of alpha-conotoxin ImI was opposite that of MII. The observation that nicotinic antagonists can differentially block synaptic transmission of B versus C neurones with opposite selectivities strongly suggests that these neurones possess distinct nicotinic receptors. 3. In addition to fast and slow B waves described by others. C waves with two temporally distinguishable components were present in our recordings. Each alpha-conotoxin affected fast and slow B waves similarly. Likewise, toxins did not discriminate between the two components of C waves. This suggests that all neurones within each major class (B or C) may have the same nicotinic receptors. 4. Synthetic forms of alpha-conotoxins MII and ImI were used in the present study. Their ease of synthesis and their specificities should make these toxins useful probes to investigate the various subtypes of neuronal nicotinic acetylcholine receptors.

  5. IMI resistance associated to crop-weed hybridization in a natural Brassica rapa population: characterization and fate.

    PubMed

    Ureta, M S; Torres Carbonell, F; Pandolfo, C; Presotto, A D; Cantamutto, M A; Poverene, M

    2017-03-01

    Wild turnip (Brassica rapa) is a common weed and a close relative to oilseed rape (Brassica napus). The Clearfield® production system is a highly adopted tool which provides an alternative solution for weed management, but its efficiency is threatened by gene transfer from crop to weed relatives. Crop-weed hybrids with herbicide resistance were found in the progeny of a B. rapa population gathered from a weedy stand on the borders of an oilseed rape (B. napus) imidazolinone (IMI)-resistant crop. Interspecific hybrids were confirmed by morphological traits in the greenhouse and experimental field, survival after imazethapyr applications, DNA content through flow cytometry, and pollen viability. The transference of herbicide resistance was demonstrated even in a particular situation of pollen competition between both an herbicide-resistant crop and a non-resistant crop. However, IMI resistance was not found in further generations collected at the same location. These results verify gene transmission from oilseed rape to B. rapa in the main crop area in Argentina where resistant and susceptible varieties are found and seed loss and crop volunteers are common. Hybridization, introgression, and herbicide selection would be associated with the loss of effectiveness of IMI technology.

  6. Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches.

    PubMed

    Penêda, José Ferreira; Lima, Nuno Barros; Monteiro, Francisco; Silva, Joana Vilela; Gama, Rita; Condé, Artur

    2018-03-07

    Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. A review of articles on IMIED from the last 10 years was conducted using PubMed ® database. IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Effective plasmonic mode-size converter.

    PubMed

    Park, Hae-Ryeong; Park, Jong-Moon; Kim, Min-su; Ju, Jung Jin; Son, Jung-Han; Lee, Myung-Hyun

    2011-10-24

    Plasmonic mode-size converters (PMSCs) for long-range surface plasmon polaritons (LR-SPPs) at the wavelength of 1.55 μm are presented. The PMSC is composed of an insulator-metal-insulator waveguide (IMI-W), a laterally tapered insulator-metal-insulator-metal-insulator waveguide (LT-IMIMI-W), and an IMIMI-W in series. The mode-intensity sizes of the LR-SPPs for the IMI-W and the IMIMI-W were not only calculated using a finite element method but were also experimentally measured. The propagation losses of the IMI-W and the IMIMI-W as well as the coupling losses between them were analyzed by the cut-back method to investigate the effect of LT-IMIMI-Ws. By using the PMSC with a ~27 ° angled LT-IMIMI-W, the coupling loss between a polarization-maintaining fiber and a 3 μm-wide IMIMI-W was reduced by ~3.4 dB. Moreover, the resulting mode-intensity in the output of the PMSC was squeezed to ~35% of the mode-intensity in the input IMI-W. The PMSC may be potentially useful for bridging micro- to nano-plasmonic integrated circuits. © 2011 Optical Society of America

  8. Moral and Ethical Decision Making

    DTIC Science & Technology

    2007-07-01

    l’intermédiaire de divers navigateurs Web. L’échantillon se composait de 212 sujets, dont 121 femmes et 91 hommes , tous résidents des États-Unis. La...interrogés résidaient aux États-Unis. Parmi eux, il y avait 121 femmes et 91 hommes . La moyenne d’âge était de 47,89 ans et l’écart-type de 7,87. Le...participants de les remplir par l’intermédiaire de divers navigateurs Web. L’échantillon se composait de 212 sujets, dont 121 femmes et 91 hommes , tous

  9. Gastrointestinal motility in relation to spontaneous meal occurrence in domestic fowls.

    PubMed

    Savory, C J

    1987-10-01

    The relationship between gastrointestinal (GI) motility and spontaneous feeding activity was investigated in five immature domestic hens, by recording simultaneously their feeding and contraction of the gizzard and duodenum. Different parameters of GI motility were interrelated, and gizzard contraction frequency (GCF) was used as an overall index of motility. Significant (P less than 0.05) changes in GCF relative to mealtimes varied between individual birds and between different meal length classes. The most consistent change was a rapid increase in GCF at the start of meals, followed by a decline which usually commenced before the end of long meals, but after the end of shorter ones. The increase in GCF commenced before the start of meals in one bird which had longer inter-meal intervals than the rest. There were no consistent changes in GCF at the ends of intervals or meals that might suggest a causal association between motility and hunger and satiety. It is suggested that the observed variation in GI motility may be accounted for mainly by variation in extrinsic stimulation from the vagus nerve.

  10. Developing Exemplar Interactive Multimedia Instruction for Unmanned Aircraft System Repairers

    DTIC Science & Technology

    2017-08-01

    material and also compared the effectiveness of two different IMI design approaches used to progress the learner through the various training modules...instruction. For the Hydraulics Theory and Components, we compared the learner-controlled Interactive Multimedia Instruction and the designer ... Design Three UAS Repairer IMI modules were developed, and the effectiveness of each was compared to the current live instruction covering the

  11. Transcutaneous immunization with a novel imiquimod nanoemulsion induces superior T cell responses and virus protection.

    PubMed

    Lopez, Pamela Aranda; Denny, Mark; Hartmann, Ann-Kathrin; Alflen, Astrid; Probst, Hans Christian; von Stebut, Esther; Tenzer, Stefan; Schild, Hansjörg; Stassen, Michael; Langguth, Peter; Radsak, Markus P

    2017-09-01

    Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses. Therefore we aimed to develop a novel imiquimod solid nanoemulsion (IMI-Sol) for TCI with superior vaccination properties suited to induce high quality T cell responses for enhanced protection against infections. TCI was performed by applying a MHC class I or II restricted epitope along with IMI-Sol or Aldara (each containing 5% Imiquimod) on the shaved dorsum of C57BL/6, IL-1R, Myd88, Tlr7 or Ccr7 deficient mice. T cell responses as well as DC migration upon TCI were subsequently analyzed by flow cytometry. To determine in vivo efficacy of TCI induced immune responses, CTL responses and frequency of peptide specific T cells were evaluated on day 8 or 35 post vaccination and protection in a lymphocytic choriomeningitis virus (LCMV) infection model was assessed. TCI with the imiquimod formulation IMI-Sol displayed equal skin penetration of imiquimod compared to Aldara, but elicited superior CD8 + as well as CD4 + T cell responses. The induction of T-cell responses induced by IMI-Sol TCI was dependent on the TLR7/MyD88 pathway and independent of IL-1R. IMI-Sol TCI activated skin-derived DCs in skin-draining lymph nodes more efficiently compared to Aldara leading to enhanced protection in a LCMV infection model. Our data demonstrate that IMI-Sol TCI can overcome current limitations of previous imiquimod based TCI approaches opening new perspectives for transcutaneous vaccination strategies and allowing the use of this enhanced cutaneous drug-delivery system to be tailored for the improved prevention and treatment of infectious diseases and cancers. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  12. Retrospective Cohort Study of 4,591 Straumann Implants Placed in 2,060 Patients in Private Practice with up to 10-Year Follow-up: The Relationship Between Crestal Bone Level and Soft Tissue Condition.

    PubMed

    French, David; Cochran, David L; Ofec, Ronen

    The purpose of this report is to describe the crestal bone level (CBL) around implants of various designs, describe the peri-implant soft tissue condition, and evaluate the relationship between the two over time. This retrospective cohort study reports on 2,060 patients with 4,591 implants evaluated after 3 months; 1, 3, 5, and 7 years; and up to 10 years. Periapical radiographs were used to evaluate changes in CBL. The peri-implant soft tissue was evaluated using a modified Bleeding Index termed the Implant Mucosal Index (IMI) where: 0 = no bleeding; 1 = minimal, single-point bleeding; 2 = moderate, multipoint bleeding; 3 = profuse, multipoint bleeding; and 4 = suppuration. At 3 months, the mean CBL was 0.06 ± 0.22 mm; by 8 to 10 years, it had increased to 0.44 ± 0.81 mm. The median CBL remained stable throughout the study at < 0.1 mm. At 8 to 10 years, 15% of implants exhibited a CBL > 1.02 mm, and 5% exhibited a CBL > 2.28 mm. More than 50% of patients experienced some bleeding, as seen by an IMI ≥ 1 during follow-up. A positive correlation was found between IMI and CBL, as shown by a mean CBL after 4 years of 0.33 mm, 0.71 mm, and 1.52 mm for IMI = 2, 3, and 4, respectively. One exception was between IMI = 0 and IMI = 1, where no significant difference was found and bone loss was minimal. Bone loss, as measured by changes in CBL during the first 10 years of implant life spans, was minimal for most implants. Nevertheless, it is not unusual to observe implants with advanced bone loss. The soft tissue condition is a good indicator of bone loss. Time alone and minimal bleeding did not correlate with bone loss, but care should be taken for implants with profuse bleeding or suppuration.

  13. Development and application of LC–APCI–MS method for biomonitoring of animal and human exposure to imidacloprid.

    PubMed

    Kavvalakis, Matthaios P; Tzatzarakis, Manolis N; Theodoropoulou, Eleftheria P; Barbounis, Emmanouil G; Tsakalof, Andreas K; Tsatsakis, Aristidis M

    2013-11-01

    Imidacloprid (IMI) is a relatively new neuro-active neonicotinoid insecticide and nowadays one of the largest selling insecticides worldwide. In the present study a LC–APCI–MS based method was developed and validated for the quantification of imidacloprid and its main metabolite 6-chloronicotinic acid (6- CINA) in urine and hair specimens. The method was tested in biomonitoring of intentionally exposed animals and subsequently applied for biomonitoring of Cretan urban and rural population. The developed analytical method comprises two main steps of analytes isolation from specimen (solid– liquid extraction with methanol for hair, liquid–liquid extraction with methanol for urine) and subsequent instrumental analysis by LC–APCI–MS. The developed method was applied for the monitoring of IMI and 6-ClNA in hair and urine of laboratory animals (rabbits) intentionally fed with insecticide at low or high doses (40 and 80 mg kg(-1) weight d(-1) respectively) for 24 weeks. The analytes were detected in the regularly acquired hair and urine specimens and their found levels were proportional to the feeding dose and time of exposure with the exception of slight decline of IMI levels in high dose fed rabbits after 24 weeks of feeding. This decline can be explained by the induction of IMI metabolizing enzymes by the substrate. After testing on animal models the method was applied for pilot biomonitoring of Crete urban (n = 26) and rural (n = 32) population. Rural but not urban population is exposed to IMI with 21 positive samples (65.6%) and found median concentration 0.03 ng mg(-1). Maximum concentration detected was 27 ng mg(-1)

  14. [Invasive mould disease in haematological patients].

    PubMed

    Ruiz-Camps, Isabel; Jarque, Isidro

    2014-01-01

    Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper. Copyright © 2014. Published by Elsevier Espana.

  15. Leveraging Gaming Technology to Deliver Effective Training

    NASA Technical Reports Server (NTRS)

    Cimino, James D.

    2011-01-01

    The best way to engage a soldier is to present them with training content consistent with their learning preference. Blended Interactive Multimedia Instruction (IMI) can be used to leach soldiers what they need to do, how to do each step, and utilize a COTS game engine to actually practices the skills learned. Blended IMI provides an enjoyable experience for the soldier, thereby increasing retention rates and motivation while decreasing the time to subject mastery. And now mobile devices have emerged as an exciting new platform, literally placing the training into the soldier's hands. In this paper, we will discuss how we leveraged commercial game engine technology, tightly integrated with the Blended IMI, to train soldiers on both laptops and mobile devices. We will provide a recent case study of how this training is being utilized, benefits and student/instructor feedback.

  16. Risk factors associated with bacteriological cure, new infection, and incidence of clinical mastitis after dry cow therapy with three different antibiotics.

    PubMed

    Gundelach, Yasmin; Kalscheuer, Elke; Hamann, Henning; Hoedemaker, Martina

    2011-09-01

    Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status.

  17. Risk factors associated with bacteriological cure, new infection, and incidence of clinical mastitis after dry cow therapy with three different antibiotics

    PubMed Central

    Gundelach, Yasmin; Kalscheuer, Elke; Hamann, Henning

    2011-01-01

    Factors affecting bacteriological cure rates (BCR) and new intramammary infections (IMI) during the dry period as well as clinical mastitis (CM) during early lactation were investigated in 414 German Holstein dairy cows receiving dry cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000 IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n = 136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n = 143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%, respectively. The three antibiotic treatments differed only in BCR, with cloxacillin yielding better results than the others. Udder quarters from cows with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes in udder tissues were linked to a lower BCR and were associated with a higher risk of CM during early lactation. The risk of CM at calving was higher in udder quarters with unspecific or subclinical mastitis before drying off. In conclusion, with antibiotic dry cow therapy, age and health status of the udder appear to be major determinants of IMI and CM during the dry period and early lactation, while BCR was associated with the antibiotic type and udder tissue status. PMID:21897095

  18. Testing fungus impregnated cloths for the control of adult Aedes aegypti under natural conditions.

    PubMed

    Paula, Adriano R; Carolino, Aline T; Silva, Carlos P; Pereira, César R; Samuels, Richard I

    2013-09-08

    Entomopathogenic fungi could be useful tools for reducing populations of the dengue mosquito Aedes aegypti. Here the efficiency of fungus (Metarhizium anisopliae) impregnated cloths (with and without imidacloprid [IMI]) was evaluated against adult A. aegypti in simulated human dwellings. Behaviour of mosquitoes in the presence of black cloths was also investigated. When mosquitoes were released into the test rooms, the lowest survival rates (38%) were seen when five black cloths impregnated with conidia of ESALQ 818 + 10 ppm IMI were fixed under tables and chairs. This result was significantly lower than the survival rate recorded when cloths were impregnated with ESALQ 818 alone (44%) or ESALQ 818 + 0.1 ppm IMI (43%). Blood fed A. aegypti had lower landing frequencies on black cloths than sucrose fed insects during the first 24 h following feeding, which may have been due to reduced flight activity. Few mosquitoes (4-5%) were observed to land on the cloths during the hours of darkness. The landing pattern of sucrose-fed mosquitoes on non-treated and fungus-treated cloths was similar. The synergism between M. anisopliae and IMI significantly reduced Aedes survival in simulated field conditions. The use of fungus impregnated cloths is a promising point source application method for the control of adult A. aegypti.

  19. Maternal-fetal disease information as a source of exercise motivation during pregnancy.

    PubMed

    Gaston, Anca; Prapavessis, Harry

    2009-11-01

    A Protection Motivation Theory (PMT) framework was used to examine whether information about the role of exercise in preventing maternal-fetal disease served as a meaningful source of exercise motivation. Pregnant women (n = 208) were randomly assigned into one of three conditions: PMT, attention control, and noncontact control. Women in the PMT group read a brochure about the benefits of exercise during pregnancy incorporating the major components of PMT; perceived vulnerability (PV), perceived severity (PS), response efficacy (RE), and self-efficacy (SE). Participants in the attention-control condition read a brochure about diet. Following treatment, all participants completed measures of their beliefs toward maternal-fetal disease and exercise, goal intention (GI), and implementation intention (IMI). One week later, a measure of self-reported exercise behavior was collected. Main outcome measures were PMT variables (PV, PS, RE, and SE), GI, IMI, and follow-up physical activity. Participants assigned to the PMT-present group reported significantly higher PS, RE, SE, GI, and increased exercise behavior. PS, RE, and SE predicted GI, GI predicted IMI, and IMI predicted exercise behavior. Information grounded in PMT is effective in influencing pregnant women's beliefs and intentions as well as changing their initial behavior. PsycINFO Database Record (c) 2009 APA, all rights reserved.

  20. Nā Liko Noelo: a program to develop Native Hawaiian researchers

    PubMed Central

    Tsark, JoAnn ‘Umilani; Braun, Kathryn L.

    2010-01-01

    Native Hawaiians are underrepresented in health research. They also have expressed dissatisfaction with the way in which many non-native researchers have formulated research questions, conducted research, and disseminated findings about Native Hawaiians. ‘Imi Hale - Native Hawaiian Cancer Network was funded by the National Cancer Institute to increase research training and mentorship opportunities for Native Hawaiians. To this end, ‘Imi Hale has followed principles of community-based participatory research to engage community members in identifying research priorities and assuring that research is beneficial, and not harmful, to Native Hawaiians. Developing indigenous researchers is a cornerstone of the program and, in its first 4 years ‘Imi Hale enrolled 78 Native Hawaiian “budding researchers (called Nā Liko Noelo in Hawaiian), of which 40 (68%) have participated in at least one training and 28 (36%) have served as investigators, 40 (51%) as research assistants, and 10 (13%) as mentors on cancer prevention and control studies. The major challenge for Nā Liko Noelo is finding the time needed to devote to research and writing scientific papers, as most have competing professional and personal obligations. Program evaluation efforts suggest, however, that ‘Imi Hale and its Nā Liko Noelo program are well accepted and are helping develop a cadré of community-sensitive indigenous Hawaiian researchers. PMID:16281705

  1. Plasmodium falciparum: differing effects of non-esterified fatty acids and phospholipids on intraerythrocytic growth in serum-free medium.

    PubMed

    Asahi, Hiroko; Izumiyama, Shinji; Tolba, Mohammed Essa Marghany; Kwansa-Bentum, Bethel

    2011-03-01

    Different combinations of non-esterified fatty acids (NEFA) had variable effects on intraerythrocytic growth of Plasmodium falciparum. All stages of the parasite cultured in medium supplemented with cis-9-octadecenoic acid (C18:1-cis-9), hexadecanoic acid (C16:0), phospholipids (Pld) and bovine albumin free of NEFA were similar to those grown in complete growth medium. Three typical growth patterns indicating suppressed schizogony (SS), suppressed formation of merozoites (SMF), and inhibited invasion of merozoites (IMI) resulted from culture in other combinations of lipids. Unsaturated or saturated NEFA with longer or shorter carbon chains than C18:1-cis-9 or C16:0, higher degree of unsaturation, and trans-forms mainly resulted in SS and SMF effects. However, IMI or partial IMI was observed with tetradecanoic acid or octadecanoic acid enriched with C18:1-cis-9, and cis-9-hexadecenoic acid plus C16:0. Isoforms of C18:1-cis-9 also mainly resulted in partial IMI. SMF also occurred with C18:1-cis-9 plus C16:0 in the absence of Pld. Thus different NEFA exerted distinct roles in erythrocytic growth of the parasite by sustaining development at different stages. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Feeding behavior as an early predictor of bovine respiratory disease in North American feedlot systems.

    PubMed

    Wolfger, B; Schwartzkopf-Genswein, K S; Barkema, H W; Pajor, E A; Levy, M; Orsel, K

    2015-01-01

    Bovine respiratory disease (BRD), which can cause substantial losses for feedlot operations, is often difficult to detect based solely on visual observations. The objectives of the current study were to determine a BRD case identification based on clinical and laboratory parameters and assess the value of feeding behavior for early detection of BRD. Auction-derived, mixed-breed beef steers (n = 213) with an average arrival weight of 294 kg were placed at a southern Alberta commercial feedlot equipped with an automated feed bunk monitoring system. Feeding behavior was recorded continuously (1-s intervals) for 5 wk after arrival and summarized into meals. Meals were defined as feeding events that were interrupted by less than 300 s nonfeeding. Meal intake (g) and meal time (min) were further summarized into daily mean, minimum, maximum, and sum and, together with frequency of meals per day, were fit into a discrete survival time analysis with a conditional log-log link. Feedlot staff visually evaluated (pen-checked) health status twice daily. Within 35 d after arrival, 76% (n = 165) of the steers had 1 or more clinical signs of BRD (reluctance to move, crusted nose, nasal or ocular discharge, drooped ears or head, and gaunt appearance). Whereas 41 blood samples could not be processed due to immediate freezing, for 124 of these steers, complete and differential blood cell count, total serum protein, plasma fibrinogen, serum concentration of haptoglobin (HP), and serum amyloid A (SAA) were determined. The disease definition for BRD was a rectal temperature ≥ 40.0°C, at least 2 clinical signs of BRD, and HP > 0.15 mg/mL. It was noteworthy that 94% of the 124 steers identified by the feedlot staff with clinical signs of BRD had HP > 0.15 mg/mL. An increase in mean meal intake, frequency, and mean inter-meal interval was associated with a decreased hazard for developing BRD 7 d before visual identification (P < 0.001). Furthermore, increased mean mealtime, frequency, and mean inter-meal interval were associated with a decreased BRD hazard up to 7 d before feedlot staff noticed clinical symptoms (P < 0.001). In conclusion, mean intake per meal as well as mean meal time and frequency of meals could be used to predict the hazard of BRD in feedlot cattle 7 d before visual detection and could be considered in commercial feedlot settings once a predictive algorithm has been developed.

  3. Measurement of precipitation induced FUV emission and Geocoronal Lyman Alpha from the IMI mission

    NASA Technical Reports Server (NTRS)

    Mende, Stephen B.; Fuselier, S. A.; Rairden, R. L.

    1995-01-01

    This final report describes the activities of the Lockheed Martin Palo Alto Research Laboratory in studying the measurement of ion and electron precipitation induced Far Ultra-Violet (FUV) emissions and Geocoronal Lyman Alpha for the NASA Inner Magnetospheric Imager (IMI) mission. this study examined promising techniques that may allow combining several FUV instruments that would separately measure proton aurora, electron aurora, and geocoronal Lyman alpha into a single instrument operated on a spinning spacecraft. The study consisted of two parts. First, the geocoronal Lyman alpha, proton aurora, and electron aurora emissions were modeled to determine instrument requirements. Second, several promising techniques were investigated to determine if they were suitable for use in an IMI-type mission. Among the techniques investigated were the Hydrogen gas cell for eliminating cold geocoronal Lyman alpha emissions, and a coded aperture spectrometer with sufficient resolution to separate Doppler shifted Lyman alpha components.

  4. Fatal falls in the US construction industry, 1990 to 1999.

    PubMed

    Derr, J; Forst, L; Chen, H Y; Conroy, L

    2001-10-01

    The Occupational Safety and Health Administration's (OSHA's) Integrated Management Information System (IMIS) database allows for the detailed analysis of risk factors surrounding fatal occupational events. This study used IMIS data to (1) perform a risk factor analysis of fatal construction falls, and (2) assess the impact of the February 1995 29 CFR Part 1926 Subpart M OSHA fall protection regulations for construction by calculating trends in fatal fall rates. In addition, IMIS data on fatal construction falls were compared with data from other occupational fatality surveillance systems. For falls in construction, the study identified several demographic factors that may indicate increased risk. A statistically significant downward trend in fatal falls was evident in all construction and within several construction categories during the decade. Although the study failed to show a statistically significant intervention effect from the new OSHA regulations, it may have lacked the power to do so.

  5. Musical obsessions: a comprehensive review of neglected clinical phenomena.

    PubMed

    Taylor, Steven; McKay, Dean; Miguel, Euripedes C; De Mathis, Maria Alice; Andrade, Chittaranjan; Ahuja, Niraj; Sookman, Debbie; Kwon, Jun Soo; Huh, Min Jung; Riemann, Bradley C; Cottraux, Jean; O'Connor, Kieron; Hale, Lisa R; Abramowitz, Jonathan S; Fontenelle, Leonardo F; Storch, Eric A

    2014-08-01

    Intrusive musical imagery (IMI) consists of involuntarily recalled, short, looping fragments of melodies. Musical obsessions are distressing, impairing forms of IMI that merit investigation in their own right and, more generally, research into these phenomena may broaden our understanding of obsessive-compulsive disorder (OCD), which is phenomenologically and etiologically heterogeneous. We present the first comprehensive review of musical obsessions, based on the largest set of case descriptions ever assembled (N=96). Characteristics of musical obsessions are described and compared with normal IMI, musical hallucinations, and visual obsessional imagery. Assessment, differential diagnosis, comorbidity, etiologic hypotheses, and treatments are described. Musical obsessions may be under-diagnosed because they are not adequately assessed by current measures of OCD. Musical obsessions have been misdiagnosed as psychotic phenomena, which has led to ineffective treatment. Accurate diagnosis is important for appropriate treatment. Musical obsessions may respond to treatments that are not recommended for prototypic OCD symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Surveillance of occupational noise exposures using OSHA's Integrated Management Information System.

    PubMed

    Middendorf, Paul J

    2004-11-01

    Exposure to noise has long been known to cause hearing loss, and is an ubiquitous problem in workplaces. Occupational noise exposures for industries stored in the Occupational Safety and Health Administration's (OSHA) Integrated Management Information System (IMIS) can be used to identify temporal and industrial trends of noise exposure to anticipate changes in rates of hearing loss. The noise records in OSHA's IMIS database for 1979-1999 were extracted by major industry division and measurement criteria. The noise exposures were summarized by year, industry, and employment size. The majority of records are from Manufacturing and Services. Exposures in Manufacturing and Services have decreased during the period, except that PEL exposures measured by federal enforcement increased from 1995 to 1999. Noise exposures in manufacturing have been reduced since the late 1970s, except those documented by federal enforcement. Noise exposure data outside manufacturing is not well represented in IMIS. Copyright 2004 Wiley-Liss, Inc.

  7. Effects of escitalopram and imipramine on cocaine reinforcement and drug-seeking behaviors in a rat model of depression.

    PubMed

    Jastrzębska, Joanna; Frankowska, Małgorzata; Suder, Agata; Wydra, Karolina; Nowak, Ewa; Filip, Małgorzata; Przegaliński, Edmund

    2017-10-15

    Depression and substance cocaine abuse are disorders with a high frequency of comorbidity. In the present study, we combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in rats to investigate the effects of two antidepressant drugs, escitalopram (ESC) and imipramine (IMI), with the goal of determining whether these drugs altered cocaine-induced reinforcement and seeking behaviors. Acute administration of IMI (2.5-30mg/kg) reduced the cocaine reinforcement in OBX and SHAM rats. Moreover, IMI effectively reduced the cocaine-seeking behavior after the drug acute or repeated administration during extinction training in OBX rats and SHAM-operated controls. By contrast, acutely administered ESC (2.5-20mg/kg) did not alter cocaine reinforcement in OBX rats or SHAM-operated controls. The lack of ESC effects was also demonstrated during reinstatement tests to study drug-seeking behavior after ESC repeated daily treatment during extinction trials. However, acute treatment with ESC dose-dependently decreased the cocaine-seeking behavior and relapse triggered by cocaine priming or drug-associated conditioned cues in both OBX and SHAM rats. These results indicate the cocaine anti-reinforcement and anti-seeking efficacy of the two antidepressant drugs studied here. However, the mechanisms for the IMI and ESC activity should be clarified in further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Discovery of the target for immunomodulatory drugs (IMiDs).

    PubMed

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2016-05-01

    Half a century ago, the sedative thalidomide caused a serious drug disaster because of its teratogenicity and was withdrawn from the market. However, thalidomide, which has returned to the market, is now used for the treatment of leprosy and multiple myeloma (MM) under strict control. The mechanism of thalidomide action had been a long-standing question. We developed a new affinity bead technology and identified cereblon (CRBN) as a thalidomide-binding protein. We found that CRBN functions as a substrate receptor of an E3 cullin-Ring ligase complex 4 (CRL4) and is a primary target of thalidomide teratogenicity. Recently, new thalidomide derivatives, called immunomodulatory drugs (IMiDs), have been developed by Celgene. Among them, lenalidomide (Len) and pomalidomide (Pom) were shown to exert strong therapeutic effects against MM. It was found that Len and Pom both bind CRBN-CRL4 and recruit neomorphic substrates (Ikaros and Aiolos). More recently it was reported that casein kinase 1a (Ck1a) was identified as a substrate for CRBN-CRL4 in the presence of Len, but not Pom. Ck1a breakdown explains why Len is specifically effective for myelodysplastic syndrome with 5q deletion. It is now proposed that binding of IMiDs to CRBN appears to alter the substrate specificity of CRBN-CRL4. In this review, we introduce recent findings on IMiDs.

  9. Nicotine-Like Effects of the Neonicotinoid Insecticides Acetamiprid and Imidacloprid on Cerebellar Neurons from Neonatal Rats

    PubMed Central

    Kimura-Kuroda, Junko; Komuta, Yukari; Kuroda, Yoichiro; Hayashi, Masaharu; Kawano, Hitoshi

    2012-01-01

    Background Acetamiprid (ACE) and imidacloprid (IMI) belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs). Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development. Methodology/Principal Findings Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment—including proliferation, migration, differentiation, and morphological and functional maturation—can be observed in vitro. Using these cultures, an excitatory Ca2+-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca2+ influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca2+ influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine. Conclusions/Significance This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian nAChRs at concentrations greater than 1 µM. Therefore, the neonicotinoids may adversely affect human health, especially the developing brain. PMID:22393406

  10. Thalidomide and its analogues have distinct and opposing effects on TNF-α and TNFR2 during co-stimulation of both CD4+ and CD8+ T cells

    PubMed Central

    MARRIOTT, J B; CLARKE, I A; DREDGE, K; MULLER, G; STIRLING, D; DALGLEISH, A G

    2002-01-01

    Thalidomide (Thd) is clinically useful in a number of conditions where its efficacy is probably related to its anti-TNF-α activity. More recently, Thd has also been shown to co-stimulate T cells and second generation co-stimulatory (IMiD™) analogues are currently being assessed in the treatment of cancer patients. However, in contrast to their known suppressive effects during inflammatory stimuli, the effects of Thd/IMiDs on TNF-α and TNF receptors (TNFRs) during T cell co-stimulation are not known. We sought to determine the effect of Thd, two clinically relevant IMiDs (CC-4047, ACTIMID™ and CC-5013, REVIMID™) and a non-stimulatory SelCID analogue (CC-3052) on TNF-α production and on the expression and shedding of TNFRs during co-stimulation. We found that co-stimulation of PBMC with Thd/IMiDs, but not CC-3052, prevented αCD3-induced T cell surface expression of TNFR2 and thereby reduced soluble TNFR2 (sTNFR2) levels. However, there was no effect on total (surface/intracellular) TNFR2 protein expression, suggesting inhibition of trafficking to the cell membrane. The extent of co-stimulation by Thd/IMiDs (assessed by CD69/CD25 expression and IL-2/sIL-2Rα production) was similar for CD4+ and CD8+ T lymphocytes and correlated with TNFR2 inhibition. Co-stimulation, but not the early inhibitory effect on TNFR2, was IL-2-dependent and led to increased TNF-α production by both CD4+ and CD8+ T lymphocytes. The clinical relevance of this observation was confirmed by the elevation of serum TNF-α during REVIMID™ treatment of patients with advanced cancer. Together, these results suggest a possible role for TNF-mediated events during co-stimulation and contrast with the TNF inhibitory effects of Thd and its analogues during inflammatory stimuli. PMID:12296856

  11. IMIS desktop & smartphone software solutions for monitoring spacecrafts' payload from anywhere

    NASA Astrophysics Data System (ADS)

    Baroukh, J.; Queyrut, O.; Airaud, J.

    In the past years, the demand for satellite remote operations has increased guided by on one hand, the will to reduce operations cost (on-call operators out of business hours), and on the other hand, the development of cooperation space missions resulting in a world wide distribution of engineers and science team members. Only a few off-the-shelf solutions exist to fulfill the need of remote payload monitoring, and they mainly use proprietary devices. The recent advent of mobile technologies (laptops, smartphones and tablets) as well as the worldwide deployment of broadband networks (3G, Wi-Fi hotspots), has opened up a technical window that brings new options. As part of the Mars Science Laboratory (MSL) mission, the Centre National D'Etudes Spatiales (CNES, the French space agency) has developed a new software solution for monitoring spacecraft payloads. The Instrument Monitoring Interactive Software (IMIS) offers state-of-the-art operational features for payload monitoring, and can be accessed remotely. It was conceived as a generic tool that can be used for heterogeneous payloads and missions. IMIS was designed as a classical client/server architecture. The server is hosted at CNES and acts as a data provider while two different kinds of clients are available depending on the level of mobility required. The first one is a rich client application, built on Eclipse framework, which can be installed on usual operating systems and communicates with the server through the Internet. The second one is a smartphone application for any Android platform, connected to the server thanks to the mobile broadband network or a Wi-Fi connection. This second client is mainly devoted to on-call operations and thus only contains a subset of the IMIS functionalities. This paper describes the operational context, including security aspects, that led IMIS development, presents the selected software architecture and details the various features of both clients: the desktop and the sm- rtphone application.

  12. Genetic and Quantitative Trait Locus Analysis for Bio-Oil Compounds after Fast Pyrolysis in Maize Cobs.

    PubMed

    Jeffrey, Brandon; Kuzhiyil, Najeeb; de Leon, Natalia; Lübberstedt, Thomas

    2016-01-01

    Fast pyrolysis has been identified as one of the biorenewable conversion platforms that could be a part of an alternative energy future, but it has not yet received the same attention as cellulosic ethanol in the analysis of genetic inheritance within potential feedstocks such as maize. Ten bio-oil compounds were measured via pyrolysis/gas chromatography-mass spectrometry (Py/GC-MS) in maize cobs. 184 recombinant inbred lines (RILs) of the intermated B73 x Mo17 (IBM) Syn4 population were analyzed in two environments, using 1339 markers, for quantitative trait locus (QTL) mapping. QTL mapping was performed using composite interval mapping with significance thresholds established by 1000 permutations at α = 0.05. 50 QTL were found in total across those ten traits with R2 values ranging from 1.7 to 5.8%, indicating a complex quantitative inheritance of these traits.

  13. Immunomodulation of multiple myeloma.

    PubMed

    Tohnya, Tanyifor M; Figg, William D

    2004-11-01

    Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

  14. The combination of huperzine A and imidazenil is an effective strategy to prevent diisopropyl fluorophosphate toxicity in mice.

    PubMed

    Pibiri, Fabio; Kozikowski, Alan P; Pinna, Graziano; Auta, James; Kadriu, Bashkim; Costa, Erminio; Guidotti, Alessandro

    2008-09-16

    Diisopropyl fluorophosphate (DFP) causes neurotoxicity related to an irreversible inhibition of acetylcholinesterase (AChE). Management of this intoxication includes: (i) pretreatment with reversible blockers of AChE, (ii) blockade of muscarinic receptors with atropine, and (iii) facilitation of GABA(A) receptor signal transduction by benzodiazepines. The major disadvantage associated with this treatment combination is that it must to be repeated frequently and, in some cases, protractedly. Also, the use of diazepam (DZP) and congeners includes unwanted side effects, including sedation, amnesia, cardiorespiratory depression, and anticonvulsive tolerance. To avoid these treatment complications but safely protect against DFP-induced seizures and other CNS toxicity, we adopted the strategy of administering mice with (i) small doses of huperzine A (HUP), a reversible and long-lasting (half-life approximately 5 h) inhibitor of AChE, and (ii) imidazenil (IMI), a potent positive allosteric modulator of GABA action selective for alpha(5)-containing GABA(A) receptors. Coadministration of HUP (50 microg/kg s.c., 15 min before DFP) with IMI (2 mg/kg s.c., 30 min before DFP) prevents DFP-induced convulsions and the associated neuronal damage and mortality, allowing complete recovery within 18-24 h. In HUP-pretreated mice, the ED(50) of IMI to block DFP-induced mortality is approximately 10 times lower than that of DZP and is devoid of sedation. Our data show that a combination of HUP with IMI is a prophylactic, potent, and safe therapeutic strategy to overcome DFP toxicity.

  15. The combination of huperzine A and imidazenil is an effective strategy to prevent diisopropyl fluorophosphate toxicity in mice

    PubMed Central

    Pibiri, Fabio; Kozikowski, Alan P.; Pinna, Graziano; Auta, James; Kadriu, Bashkim; Costa, Erminio; Guidotti, Alessandro

    2008-01-01

    Diisopropyl fluorophosphate (DFP) causes neurotoxicity related to an irreversible inhibition of acetylcholinesterase (AChE). Management of this intoxication includes: (i) pretreatment with reversible blockers of AChE, (ii) blockade of muscarinic receptors with atropine, and (iii) facilitation of GABAA receptor signal transduction by benzodiazepines. The major disadvantage associated with this treatment combination is that it must to be repeated frequently and, in some cases, protractedly. Also, the use of diazepam (DZP) and congeners includes unwanted side effects, including sedation, amnesia, cardiorespiratory depression, and anticonvulsive tolerance. To avoid these treatment complications but safely protect against DFP-induced seizures and other CNS toxicity, we adopted the strategy of administering mice with (i) small doses of huperzine A (HUP), a reversible and long-lasting (half-life ≈5 h) inhibitor of AChE, and (ii) imidazenil (IMI), a potent positive allosteric modulator of GABA action selective for α5-containing GABAA receptors. Coadministration of HUP (50 μg/kg s.c., 15 min before DFP) with IMI (2 mg/kg s.c., 30 min before DFP) prevents DFP-induced convulsions and the associated neuronal damage and mortality, allowing complete recovery within 18–24 h. In HUP-pretreated mice, the ED50 of IMI to block DFP-induced mortality is ≈10 times lower than that of DZP and is devoid of sedation. Our data show that a combination of HUP with IMI is a prophylactic, potent, and safe therapeutic strategy to overcome DFP toxicity. PMID:18784370

  16. Bayesian estimation of test characteristics of real-time PCR, bacteriological culture and California mastitis test for diagnosis of intramammary infections with Staphylococcus aureus in dairy cattle at routine milk recordings.

    PubMed

    Mahmmod, Yasser S; Toft, Nils; Katholm, Jørgen; Grønbæk, Carsten; Klaas, Ilka C

    2013-11-01

    Danish farmers can order a real-time PCR mastitis diagnostic test on routinely taken cow-level samples from milk recordings. Validation of its performance in comparison to conventional mastitis diagnostics under field conditions is essential for efficient control of intramammary infections (IMI) with Staphylococcus aureus (S. aureus). Therefore, the objective of this study was to estimate the sensitivity (Se) and specificity (Sp) of real-time PCR, bacterial culture (BC) and California mastitis test (CMT) for the diagnosis of the naturally occurring IMI with S. aureus in routinely collected milk samples using latent class analysis (LCA) to avoid the assumption of a perfect reference test. Using systematic random sampling, a total of 609 lactating dairy cows were selected from 6 dairy herds with bulk tank milk PCR cycle threshold (Ct) value ≤39 for S. aureus. At routine milk recordings, automatically obtained cow-level (composite) milk samples were analyzed by PCR and at the same milking, 2436 quarter milk samples were collected aseptically for BC and CMT. Results showed that 140 cows (23%) were positive for S. aureus IMI by BC while 170 cows (28%) were positive by PCR. Estimates of Se and Sp for PCR were higher than test estimates of BC and CMT. SeCMT was higher than SeBC however, SpBC was higher than SpCMT. SePCR was 91%, while SeBC was 53%, and SeCMT was 61%. SpPCR was 99%, while SpBC was 89%, and SpCMT was 65%. In conclusion, PCR has a higher performance than the conventional diagnostic tests (BC and CMT) suggesting its usefulness as a routine test for accurate diagnosis of S. aureus IMI from dairy cows at routine milk recordings. The use of LCA provided estimates of the test characteristics for two currently diagnostic tests (BC, CMT) and a novel technique (real-time PCR) for diagnosing S. aureus IMI under field conditions at routine milk recordings in Denmark. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells.

    PubMed

    Marriott, J B; Clarke, I A; Dredge, K; Muller, G; Stirling, D; Dalgleish, A G

    2002-10-01

    Thalidomide (Thd) is clinically useful in a number of conditions where its efficacy is probably related to its anti-TNF-alpha activity. More recently, Thd has also been shown to co-stimulate T cells and second generation co-stimulatory (IMiD trade mark ) analogues are currently being assessed in the treatment of cancer patients. However, in contrast to their known suppressive effects during inflammatory stimuli, the effects of Thd/IMiDs on TNF-alpha and TNF receptors (TNFRs) during T cell co-stimulation are not known. We sought to determine the effect of Thd, two clinically relevant IMiDs (CC-4047, ACTIMID trade mark and CC-5013, REVIMID trade mark ) and a non-stimulatory SelCID analogue (CC-3052) on TNF-alpha production and on the expression and shedding of TNFRs during co-stimulation. We found that co-stimulation of PBMC with Thd/IMiDs, but not CC-3052, prevented alphaCD3-induced T cell surface expression of TNFR2 and thereby reduced soluble TNFR2 (sTNFR2) levels. However, there was no effect on total (surface/intracellular) TNFR2 protein expression, suggesting inhibition of trafficking to the cell membrane. The extent of co-stimulation by Thd/IMiDs (assessed by CD69/CD25 expression and IL-2/sIL-2Ralpha production) was similar for CD4+ and CD8+ T lymphocytes and correlated with TNFR2 inhibition. Co-stimulation, but not the early inhibitory effect on TNFR2, was IL-2-dependent and led to increased TNF-alpha production by both CD4+ and CD8+ T lymphocytes. The clinical relevance of this observation was confirmed by the elevation of serum TNF-alpha during REVIMID trade mark treatment of patients with advanced cancer. Together, these results suggest a possible role for TNF-mediated events during co-stimulation and contrast with the TNF inhibitory effects of Thd and its analogues during inflammatory stimuli.

  18. Neonicotinoid insecticides induce salicylate-associated plant defense responses

    PubMed Central

    Ford, Kevin A.; Casida, John E.; Chandran, Divya; Gulevich, Alexander G.; Okrent, Rachel A.; Durkin, Kathleen A.; Sarpong, Richmond; Bunnelle, Eric M.; Wildermuth, Mary C.

    2010-01-01

    Neonicotinoid insecticides control crop pests based on their action as agonists at the insect nicotinic acetylcholine receptor, which accepts chloropyridinyl- and chlorothiazolyl-analogs almost equally well. In some cases, these compounds have also been reported to enhance plant vigor and (a)biotic stress tolerance, independent of their insecticidal function. However, this mode of action has not been defined. Using Arabidopsis thaliana, we show that the neonicotinoid compounds, imidacloprid (IMI) and clothianidin (CLO), via their 6-chloropyridinyl-3-carboxylic acid and 2-chlorothiazolyl-5-carboxylic acid metabolites, respectively, induce salicylic acid (SA)-associated plant responses. SA is a phytohormone best known for its role in plant defense against pathogens and as an inducer of systemic acquired resistance; however, it can also modulate abiotic stress responses. These neonicotinoids effect a similar global transcriptional response to that of SA, including genes involved in (a)biotic stress response. Furthermore, similar to SA, IMI and CLO induce systemic acquired resistance, resulting in reduced growth of a powdery mildew pathogen. The action of CLO induces the endogenous synthesis of SA via the SA biosynthetic enzyme ICS1, with ICS1 required for CLO-induced accumulation of SA, expression of the SA marker PR1, and fully enhanced resistance to powdery mildew. In contrast, the action of IMI does not induce endogenous synthesis of SA. Instead, IMI is further bioactivated to 6-chloro-2-hydroxypyridinyl-3-carboxylic acid, which is shown here to be a potent inducer of PR1 and inhibitor of SA-sensitive enzymes. Thus, via different mechanisms, these chloropyridinyl- and chlorothiazolyl-neonicotinoids induce SA responses associated with enhanced stress tolerance. PMID:20876120

  19. Theoretical and spectroscopic studies of a tricyclic antidepressant, imipramine hydrochloride

    NASA Astrophysics Data System (ADS)

    Sagdinc, S. G.; Azkeskin, Caner; Eşme, A.

    2018-06-01

    Imipramine hydrochloride ([H-IMI]Cl), C19H24N2.HCl, is the prototypic tricyclic antidepressant (TCA) inhibitor of norepinephrine and serotonin neuronal reuptake. The molecular structure, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, linear and non-linear optical (NLO) properties of [H-IMI]Cl have been investigated using the density functional theory (DFT) calculations with the B3LYP level at the 6‒311++G(d,p) basis set. The UV-Vis spectra for [H-IMI]Cl were experimentally studied in water and methanol. TD‒DFT calculations in water and methanol were employed to investigate the absorption wavelengths (λ), excitation energies (E), and oscillator strengths (f) for the UV-Vis analysis and the major contributions to the electronic transitions. From NBO analysis, the orbitals with the stabilization energy E(2) of 192.15 kcal/mol are π*(C5sbnd C18) as donor NBO and π*(C19sbnd C20) as acceptor NBO. The FT‒IR (4000‒400 cm-1) and FT‒Raman (3500-50 cm-1) spectra have been measured and analyzed. The assignment of bands observed vibrational spectra have been made by comparison of its calculated theoretical vibrational frequencies obtained using the DFT/B3LYP/6‒311++G(d,p) method. The detailed vibrational assignments were performed with the DFT calculation, and the potential energy distribution (PED) of [H-IMI]Cl was obtained by the Vibrational Energy Distribution Analysis 4 (VEDA4) program. The scaled frequencies resulted in good agreement with the observed spectral patterns.

  20. Texture orientation-based algorithm for detecting infrared maritime targets.

    PubMed

    Wang, Bin; Dong, Lili; Zhao, Ming; Wu, Houde; Xu, Wenhai

    2015-05-20

    Infrared maritime target detection is a key technology for maritime target searching systems. However, in infrared maritime images (IMIs) taken under complicated sea conditions, background clutters, such as ocean waves, clouds or sea fog, usually have high intensity that can easily overwhelm the brightness of real targets, which is difficult for traditional target detection algorithms to deal with. To mitigate this problem, this paper proposes a novel target detection algorithm based on texture orientation. This algorithm first extracts suspected targets by analyzing the intersubband correlation between horizontal and vertical wavelet subbands of the original IMI on the first scale. Then the self-adaptive wavelet threshold denoising and local singularity analysis of the original IMI is combined to remove false alarms further. Experiments show that compared with traditional algorithms, this algorithm can suppress background clutter much better and realize better single-frame detection for infrared maritime targets. Besides, in order to guarantee accurate target extraction further, the pipeline-filtering algorithm is adopted to eliminate residual false alarms. The high practical value and applicability of this proposed strategy is backed strongly by experimental data acquired under different environmental conditions.

  1. New Topical Treatment Options for Actinic Keratosis: A Systematic Review.

    PubMed

    Stockfleth, Eggert; Sibbring, Gillian C; Alarcon, Ivette

    2016-01-01

    This systematic review compared the relative efficacy of 5-fluorouracil 0.5% in salicylic acid 10% (5-FU/SA), ingenol mebutate (IMB) and imiquimod 2.5%/3.75% (IMI) for actinic keratosis on the face, forehead or scalp. Only 11 publications, relating to 7 randomised controlled trials, met inclusion criteria and it was only possible to compare the effect of all 3 treatments on complete clinical clearance, and the effect of 5-FU/SA and IMB on actinic keratosis recurrence rate. Despite a higher vehicle response rate for 5-FU/SA, complete clinical clearance was higher than IMB and IMI (55.4, 42.2, and 25.0-30.6/34.0-35.6%, [corrected] respectively). 5-FU/SA was also associated with lower actinic keratosis recurrence rate than IMB at 12 months post-treatment (32.7 vs. 53.9%). Although qualitative assessment suggested a numerical advantage of 5-FU/SA over IMB and IMI in terms of complete clinical clearance and sustained clearance, clinical data from longer term trials, with comparable outcome measures, are required to corroborate these findings.

  2. Risk factors for intramammary infections and subclinical mastitis in post-partum dairy heifers.

    PubMed

    Krömker, Volker; Pfannenschmidt, Florian; Helmke, Katherina; Andersson, Robby; Grabowski, Nils T

    2012-08-01

    The prevalence of intramammary infections (IMI) and subclinical mastitis (SCM) in 436 German Holstein heifers was put in relation with clinical findings of the udder and data regarding individual rearing and housing conditions of the animals. The clinical examination took place on the day of the livestock auction (at approximately 41 d in milk, DIM). On that day, 31% of the heifers had IMI in at least one quarter, and 18% of all quarters were infected. Coagulase-negative staphylococci were the most prevalent bacteria isolated, accounting for 68% of the positive samples. Data were analysed by logistic regression. Criteria such as 'juvenile intersucking', 'teats shorter than 35 mm', 'teats with a diameter <18 mm' and 'udder oedema at the day of the auction' were associated with IMI in heifers during the first 41 DIM. Loose-housing systems during pregnancy (as opposed to tie-stalls), juvenile intersucking, clinical mastitis during the first week after calving, teat diameters <18 mm, and employing organic bedding material in the stables before calving were associated with subclinical mastitis.

  3. The Inner Magnetosphere Imager mission

    NASA Technical Reports Server (NTRS)

    Gallagher, D. L.

    1994-01-01

    The Inner Magnetosphere Imager (IMI) mission will carry instruments to globally image energetic neutral atoms, far and extreme ultraviolet light, and X-rays. These imagers will see the ring current, inner plasmasheet, plasmasphere, aurora, and geocorona. With these observations it will be possible, for the first time, to develop an understanding of the global shape of the inner magnetosphere and the interrelationships between its parts. Seven instruments are currently envisioned on a single spinning spacecraft with a despun platform. IMI will be launched into an elliptical, polar orbit with an apogee of approximately 7 Earth radii altitude and perigee of 4800 km altitude.

  4. Estimation of test characteristics of real-time PCR and bacterial culture for diagnosis of subclinical intramammary infections with Streptococcus agalactiae in Danish dairy cattle in 2012 using latent class analysis.

    PubMed

    Mahmmod, Yasser S; Toft, Nils; Katholm, Jørgen; Grønbæk, Carsten; Klaas, Ilka C

    2013-05-01

    The misdiagnosis of intramammary infections (IMI) with Streptococcus agalactiae (S. agalactiae) could lead farmers to treat or cull animals unnecessarily. The objective of this field study was to estimate the sensitivity (Se) and specificity (Sp) of real-time PCR at different cut-offs for cycle threshold (Ct) values against bacterial culture (BC) for diagnosis of S. agalactiae IMI using latent class analysis to avoid the assumption of a perfect reference test. A total of 614 dairy cows were randomly selected from 6 herds with bulk tank PCR Ct value ≤ 39 for S. agalactiae and S. aureus. At milk recording, 2456 quarter milk samples were taken aseptically for BC and the routinely taken cow level milk samples were analyzed by PCR. Results showed that 53 cows (8.6%) were positive for S. agalactiae IMI by BC. Sensitivity of PCR at cut-offs; ≤ 39, ≤ 37, ≤ 34, and ≤ 32, was 96.2%, 91.9%, 87.2% and 73.9%, while Se of BC was 25.7%, 29.9%, 59.9% and 72.1%. Specificity of PCR at cut-offs; ≤ 39, ≤ 37, ≤ 34, and ≤ 32, was 96.8%, 96.9%, 96.7%, and 97.22%, while Sp of BC was 99.7%, 99.5%, 99.2%, and 98.9%. The estimated prevalence of S. agalactiae IMI by PCR was higher than the apparent prevalence at the tested cut-offs, indicating under estimation of S. agalactiae IMI in the examined dairy cows. In conclusion, Se of PCR is always higher than Se of BC at all tested cut-offs. The lower cut-off, the more comparable becomes Se of PCR and Se of BC. The changes in Se in both PCR and BC at different Ct-value cut-offs may indicate a change in the definition of the latent infection. The similar Se of both tests at cut-off ≤ 32 may indicate high concentrations of S. agalactiae viable cells, representing a cow truly/heavily infected with S. agalactiae and thus easier to detect with BC. At cut-off ≤ 39 the latent definition of infection may reflect a more general condition of cows being positive for S. agalactiae. Our findings indicate that PCR Ct-value cut-offs should be chosen according to the underlying latent infection definition of interest. Latent class analysis proposes a useful alternative to classic test evaluation of diagnostic tests used for detection of S. agalactiae IMI in milk. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Failure of combination therapy with imidocarb dipropionate and toltrazuril to clear Hepatozoon canis infection in dogs.

    PubMed

    Pasa, Serdar; Voyvoda, Huseyin; Karagenc, Tulin; Atasoy, Abidin; Gazyagci, Serkal

    2011-09-01

    Current treatments with imidocarb dipropionate for infected dogs with Hepatozoon canis do not always provide parasitological cure. The objective of this study is to determine whether concomitant use of toltrazuril may potentiate the effect of imidocarb dipropionate in the management of H. canis infection (HCI). Twelve dogs were determined to have naturally HCI based on clinical signs, identification of the parasite in blood smears, and serologic assay. The animals were allocated randomly to one of two groups (n = 6 in each group). Dogs in Imi group were given imidocarb dipropionate at a dose of 6 mg/kg body weight subcutaneously in two injections 14 days apart. Imi plus Toltra group was given imidocarb dipropionate as dose mentioned above and toltrazuril at 10 mg/kg/day orally for the first five treatment days. Clinical findings, blood counts and parasitaemia levels in blood before and 14, 28 and 56 days after the initial treatment were performed to evaluate treatment response. The overall clinical efficacy of imidocarb dipropionate with and without toltrazuril was 83.3% and 66.7%, respectively; with a mean recovery time of 21.0 and 25.6 days, respectively. A substantial main effect of time on mean PCV, Hb, WBC, neutrophil and PLT and gradual reduction of parasitaemia were significantly observed in both groups (P < 0.05), whereas no significant difference was noticed between the studied protocols. The parasitologic cure rate at the end of eight weekly observation period was 16.6% and 33.3% in Imi and Imi plus Toltra groups, respectively. Similar clinicopathologic and parasitologic responses were observed in both treated groups; thus, it was concluded that toltrazuril does not reveal additional benefit to imidocarb therapy in dogs with HCI.

  6. Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression I: bio-behavioural validation and response to imipramine.

    PubMed

    Brand, Sarel Jacobus; Harvey, Brian Herbert

    2017-08-01

    Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours. Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied. FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus. Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

  7. Short communication: Genotypic and phenotypic identification of environmental streptococci and association of Lactococcus lactis ssp. lactis with intramammary infections among different dairy farms.

    PubMed

    Werner, B; Moroni, P; Gioia, G; Lavín-Alconero, L; Yousaf, A; Charter, M E; Carter, B Moslock; Bennett, J; Nydam, D V; Welcome, F; Schukken, Y H

    2014-11-01

    Lactococcus species are counted among a large and closely related group of environmental streptococci and streptococci-like bacteria that include bovine mastitis pathogenic Streptococcus, Enterococcus, and Aerococcus species. Phenotypic and biochemical identification methods can be inaccurate and unreliable for species within this group, particularly for Lactococcus spp. As a result, the incidence of Lactococcus spp. on the farm may have been historically underreported and consequently little is known about the clinical importance of this genus as a mastitis pathogen. We used molecular genetic identification methods to accurately differentiate 60 environmental streptococci and streptococci-like bacteria isolated from cows with high somatic cell count and chronic intramammary infection (IMI; >2 somatic cell scores above 4) among 5 geographically distinct farms in New York and Minnesota that exhibited an observed increase in IMI. These isolates were phenotypically identified as Streptococcus uberis and Streptococcus spp. Genetic methods identified 42 isolates (70%) as Lactococcus lactis ssp. lactis, including all 10 isolates originally phenotypically identified as Streptococcus uberis. Antibiotic inhibition testing of all Lc. lactis ssp. lactis showed that 7 isolates were resistant to tetracycline. In the present study, a predominance of Lc. lactis ssp. lactis was identified in association with chronic, clinical bovine IMI among all 5 farms and characterized antimicrobial resistance for treatment therapies. Routine use by mastitis testing labs of molecular identification methods for environmental streptococci and streptococci-like bacteria can further define the role and prevalence of Lc. lactis ssp. lactis in association with bovine IMI and may lead to more targeted therapies. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Texture studies of hot compressed near alpha titanium alloy (IMI 834) at 1000°C with different strain rates

    NASA Astrophysics Data System (ADS)

    Kodli, B. K.; Saxena, K. K.; Dey, S. R.; Pancholi, V.; Bhattacharjee, A.

    2015-04-01

    IMI 834 Titanium alloy is a near alpha (hcp) titanium alloy used for high temperature applications with the service temperature up to 600°C. Generally, this alloy is widely used in gas turbine engine applications such as low pressure compressor discs. For these applications, good fatigue and creep properties are required, which have been noticed better in a bimodal microstructure, containing 15-20% volume fraction of primary alpha grains (αp) and remaining bcc beta (β) grains transformed secondary alpha laths (αs). The bimodal microstructure is achieved during processing of IMI 834 in the high temperature α+β region. The major issue of bimodal IMI 834 during utilization is its poor dwell fatigue life time caused by textured macrozones. Textured macrozone is the spatial accumulation of similar oriented grains in the microstructure generated during hot processing in the high temperature α+β region. Textured macrozone can be mitigated by controlling the hot deformation with certain strain rate under stable plastic conditions having β grains undergoing dynamic recrystallization. Hence, a comprehensive study is required to understand the deformation behavior of α and β grains at different strain rates in that region. Hot compression tests up to 5°% strain of the samples are performed with five different strain rates i.e. 10-3 s-1, 10-2 s-1, 10-1 s-1, 1 s-1 and 10 s-1 at 1000°C using Gleeble 3800. The resultant bimodal microstructure and the texture studies of primary alpha grains (αp) and secondary alpha laths (αs) are carried out using scanning electron microscopy (SEM)-electron back scattered diffraction (EBSD) method.

  9. Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

    PubMed Central

    Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

    2014-01-01

    The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

  10. Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

    PubMed

    Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

    2014-01-01

    The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

  11. Perspectives in the treatment of multiple myeloma.

    PubMed

    Gentile, Massimo; Recchia, Anna Grazia; Mazzone, Carla; Lucia, Eugenio; Vigna, Ernesto; Morabito, Fortunato

    2013-06-01

    The development of proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs) and advances in supportive care have considerably changed the treatment paradigm of multiple myeloma (MM) and significantly improved survival. Nevertheless, almost all patients show disease relapse and develop drug resistance. We review the prognostic stratification and therapeutic strategy for newly diagnosed MM patients. Furthermore, mechanisms of drug resistance are discussed. Data regarding newer drugs, currently undergoing examination, such as PI (carfilzomib, ONX0912, MLN9708, and marizomib), IMiDs (pomalidomide), histone deacetylase inhibitors (vorinostat and panobinostat), kinase inhibitors (temsirolimus, everolimus, and tanespimycin), and immune-based therapies (elotuzumab, siltuximab, MOR03087, and MMBT062) are reported. The use of three to four drug combination therapies including PI and IMiDs has significantly impacted on MM patient outcome. Moreover, new insights into MM biology from high-throughput technologies and availability of newer and more efficacious drugs will continue to influence our approach to MM treatment. In the immediate future molecular subgroup-specific trials using targeted agents may represent a very important step toward evaluating impact of interfering with relevant signaling pathways in MM. With the continued rapid evolution of progress in this field, MM will become a chronic illness having sustained complete response in a significant number of patients.

  12. The Inner Magnetospheric Imager (IMI): Instrument heritage and orbit viewing analysis

    NASA Astrophysics Data System (ADS)

    Wilson, Gordon R.

    1992-12-01

    For the last two years an engineering team in the Program Development Office at MSFC has been doing design studies for the proposed Inner Magnetospheric Imager (IMI) mission. This team had a need for more information about the instruments that this mission would carry so that they could get a better handle on instrument volume, mass, power, and telemetry needs as well as information to help assess the possible cost of such instruments and what technology development they would need. To get this information, an extensive literature search was conducted as well as interviews with several members of the IMI science working group. The results of this heritage survey are summarized below. There was also a need to evaluate the orbits proposed for this mission from the stand point of their suitability for viewing the various magnetospheric features that are planned for this mission. This was accomplished by first, identifying the factors which need to be considered in selecting an orbit, second, translating these considerations into specific criteria, and third, evaluating the proposed orbits against these criteria. The specifics of these criteria and the results of the orbit analysis are contained in the last section of this report.

  13. The Immunology of Mammary Gland of Dairy Ruminants between Healthy and Inflammatory Conditions

    PubMed Central

    Ezzat Alnakip, Mohamed; Quintela-Baluja, Marcos; Fernández-No, Inmaculada; Caamaño-Antelo, Sonia; Calo-Mata, Pillar; Barros-Velázquez, Jorge

    2014-01-01

    The health of dairy animals, particularly the milk-producing mammary glands, is essential to the dairy industry because of the crucial hygienic and economic aspects of ensuring production of high quality milk. Due to its high prevalence, mastitis is considered the most important threat to dairy industry, due to its impacts on animal health and milk production and thus on economic benefits. The MG is protected by several defence mechanisms that prevent microbial penetration and surveillance. However, several factors can attenuate the host immune response (IR), and the possession of various virulence and resistance factors by different mastitis-causing microorganisms greatly limits immune defences and promotes establishment of intramammary infections (IMIs). A comprehensive understanding of MG immunity in both healthy and inflammatory conditions will be an important key to understand the nature of IMIs caused by specific pathogens and greatly contributes to the development of effective control methods and appropriate detection techniques. Consequently, this review aims to provide a detailed overview of antimicrobial defences in the MG under healthy and inflammatory conditions. In this sense, we will focus on pathogen-dependent variations in IRs mounted by the host during IMI and discuss the potential ramifications of these variations. PMID:26464939

  14. Activation and modulation of human α4β2 nicotinic acetylcholine receptors by the neonicotinoids clothianidin and imidacloprid

    PubMed Central

    Li, Ping; Ann, Jason; Akk, Gustav

    2013-01-01

    Neonicotinoids are synthetic, nicotine-derived insecticides used for agricultural and household pest control. While highly effective at activating insect nicotinic receptors, many neonicotinoids are also capable of directly activating and/or modulating the activation of vertebrate nicotinic receptors. In this study, we have investigated the actions of the neonicotinoids clothianidin (CTD) and imidacloprid (IMI) on human neuronal α4β2 nicotinic acetylcholine receptors. The data demonstrate that the compounds are weak agonists of the human receptors with relative peak currents of 1–4 % of the response to 1 mM acetylcholine (ACh). Coapplication of IMI strongly inhibited currents elicited by ACh. From Schild plot analysis, we estimate that the affinity of IMI to the human α4β2 receptor is 18 µM. The application of low concentrations of CTD potentiated responses to low concentrations of ACh, suggesting that receptors occupied by one ACh and one CTD molecule have a higher gating efficacy than receptors with one ACh bound. Interestingly, subunit stoichiometry affected inhibition by CTD, with (α4)2(β2)3 receptors significantly more strongly inhibited than the (α4)3(β2)2 receptors. PMID:21538459

  15. The Inner Magnetospheric Imager (IMI): Instrument heritage and orbit viewing analysis

    NASA Technical Reports Server (NTRS)

    Wilson, Gordon R.

    1992-01-01

    For the last two years an engineering team in the Program Development Office at MSFC has been doing design studies for the proposed Inner Magnetospheric Imager (IMI) mission. This team had a need for more information about the instruments that this mission would carry so that they could get a better handle on instrument volume, mass, power, and telemetry needs as well as information to help assess the possible cost of such instruments and what technology development they would need. To get this information, an extensive literature search was conducted as well as interviews with several members of the IMI science working group. The results of this heritage survey are summarized below. There was also a need to evaluate the orbits proposed for this mission from the stand point of their suitability for viewing the various magnetospheric features that are planned for this mission. This was accomplished by first, identifying the factors which need to be considered in selecting an orbit, second, translating these considerations into specific criteria, and third, evaluating the proposed orbits against these criteria. The specifics of these criteria and the results of the orbit analysis are contained in the last section of this report.

  16. Inner Magnetosphere Imager (IMI) solar terrestrial probe class mission preliminary design study report

    NASA Technical Reports Server (NTRS)

    Hermann, M.; Johnson, L.

    1994-01-01

    For three decades, magnetospheric field and plasma measurements have been made by diverse instruments flown on spacecraft in many different orbits, widely separated in space and time, and under various solar and magnetospheric conditions. Scientists have used this information to piece together an intricate, yet incomplete view of the magnetosphere. A simultaneous global view, using various light wavelengths and energetic neutral atoms, could reveal exciting new data and help explain complex magnetospheric processes, thus providing us with a clear picture of this region of space. The George C. Marshall Space Flight Center (MSFC) is responsible for defining the IMI mission which will study this region of space. NASA's Space Physics Division of the Office of Space Science placed the IMI third in its queue of Solar Terrestrial Probe missions for launch in the 1990's. A core instrument complement of three images (with the potential addition of one or more mission enhancing instruments) will fly in an elliptical, polar earth orbit with an apogee of 44,600 km and a perigee of 4,800 km. This paper will address the mission objectives, spacecraft design consideration, interim results of the MSFC concept definition study, and future plans.

  17. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma.

    PubMed

    Hideshima, T; Cottini, F; Ohguchi, H; Jakubikova, J; Gorgun, G; Mimura, N; Tai, Y-T; Munshi, N C; Richardson, P G; Anderson, K C

    2015-05-15

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities.

  18. Vaporisation and thermal decomposition of dialkylimidazolium halide ion ionic liquids.

    PubMed

    Lovelock, Kevin R J; Armstrong, James P; Licence, Peter; Jones, Robert G

    2014-01-28

    Vaporisation and liquid phase thermal decomposition, TD, of two halide ion ionic liquids, 1-octyl-3-methylimidazolium chloride, [C8C1Im]Cl, and 1-octyl-3-methylimidazolium iodide, [C8C1Im]I, are investigated using temperature programmed desorption (TPD) line of sight mass spectrometry (LOSMS) at ultra-high vacuum (UHV). The ability to use MS to distinguish between vaporisation and TD allows the thermodynamics/kinetics of both vaporisation and TD to be investigated within the same experiments. Vaporisation of both halide ion ionic liquids is demonstrated. For both [C8C1Im]Cl and [C8C1Im]I the vapour is shown to be composed of neutral ion pairs (NIPs). The enthalpy of vaporisation at temperature T, ΔvapHT, was experimentally determined as ΔvapH455 = 151 ± 10 kJ mol(-1) for [C8C1Im]Cl and ΔvapH480 = 149 ± 8 kJ mol(-1) for [C8C1Im]I. Extrapolation of ΔvapHT to the reference temperature, 298 K, gave ΔvapH298 = 166 ± 10 kJ mol(-1) for [C8C1Im]Cl and ΔvapH298 = 167 ± 8 kJ mol(-1) for [C8C1Im]I, higher than most ΔvapH298 values measured to date for other [C8C1Im](+)-containing ionic liquids. In addition, predictions of ΔvapH298 for other halide ion ionic liquids are made. Liquid phase TD is shown to proceed via nucleophilic substitution to give two sets of products: 1-octylimidazole and methylhalide, and 1-methylimidazole and 1-octylhalide. The activation energy of TD at a temperature T, Ea,TD,T, is measured for the nucleophilic substitution of [C8C1Im]I to give methyliodide; Ea,TD,480 = 136 ± 15 kJ mol(-1). Ea,TD,T is measured for the nucleophilic substitution of [C8C1Im]Cl to give methylchloride; Ea,TD,455 = 132 ± 10 kJ mol(-1). The fact that ΔvapHT and Ea,TD,T are the same (within error) for both ionic liquids is commented upon, and conclusions are drawn as to the thermal stability of these ionic liquids.

  19. Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm.

    PubMed

    Checa, Rocío; Montoya, Ana; Ortega, Nieves; González-Fraga, José Luis; Bartolomé, Adrián; Gálvez, Rosa; Marino, Valentina; Miró, Guadalupe

    2017-03-13

    Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml. Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity. Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result. IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

  20. MICROWAVE-ACCELERATED MULTICOMPONENT REACTIONS UNDER SOLVENT-FREE CONDITIONS

    EPA Science Inventory

    The application of microwave-accelerated solventless synthetic protocols in multicomponent (MCC) reactions will be exemplified by several condensation and cyclization reactions including the rapid one-pot assembly of valuable heterocyclic compounds from in situ generated intermed...

  1. Alpha-conotoxin ImI Disrupts Central Control of Swimming in the Medicinal Leech

    PubMed Central

    Wagenaar, Daniel A.; Gonzalez, Ruben; Ries, David C.; Kristan, William B.; French, Kathleen A.

    2010-01-01

    Medicinal leeches (Hirudo spp.) swim using a metachronal, front-to-back undulation. The behavior is generated by central pattern generators (CPGs) distributed along the animal’s midbody ganglia and is coordinated by both central and peripheral mechanisms. Here we report that a component of the venom of Conus imperialis, α-conotoxin ImI, known to block nicotinic acetylcholine receptors in other species, disrupts swimming. Leeches injected with the toxin swam in circles with exaggerated dorsoventral bends and reduced forward velocity. Fictive swimming in isolated nerve cords was even more strongly disrupted, indicating that the toxin targets the CPGs and central coordination, while peripheral coordination partially rescues the behavior in intact animals. PMID:20833225

  2. Why self-controlled feedback enhances motor learning: Answers from electroencephalography and indices of motivation.

    PubMed

    Grand, Kirk F; Bruzi, Alessandro T; Dyke, Ford B; Godwin, Maurice M; Leiker, Amber M; Thompson, Andrew G; Buchanan, Taylor L; Miller, Matthew W

    2015-10-01

    It was tested whether learners who choose when to receive augmented feedback while practicing a motor skill exhibit enhanced augmented feedback processing and intrinsic motivation, along with superior learning, relative to learners who do not control their feedback. Accordingly, participants were assigned to either self-control (Self) or yoked groups and asked to practice a non-dominant arm beanbag toss. Self participants received augmented feedback at their discretion, whereas Yoked participants were given feedback schedules matched to Self counterparts. Participants' visual feedback was occluded, and when they received augmented feedback, their processing of it was indexed with the electroencephalography-derived feedback-related negativity (FRN). Participants self-reported intrinsic motivation via the Intrinsic Motivation Inventory (IMI) after practice, and completed a retention and transfer test the next day to index learning. Results partially support the hypothesis. Specifically, Self participants reported higher IMI scores, exhibited larger FRNs, and demonstrated better accuracy on the transfer test, but not on the retention test, nor did they exhibit greater consistency on the retention or transfer tests. Additionally, post-hoc multiple regression analysis indicated FRN amplitude predicted transfer test accuracy (accounting for IMI score). Results suggest self-controlled feedback schedules enhance feedback processing, which enhances the transfer of a newly acquired motor skill. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Determination of the dissociation constants (pKa) of secondary and tertiary amines in organic media by capillary electrophoresis and their role in the electrophoretic mobility order inversion.

    PubMed

    Cantu, Marcelo Delmar; Hillebranda, Sandro; Carrilho, Emanuel

    2005-03-11

    Non-aqueous capillary electrophoresis (NACE) may provide a selectivity enhancement in separations since the analyte dissociation constants (pKa) in organic media are different from those in aqueous solutions. In this work, we have studied the inversion in mobility order observed in the separation of tertiary (imipramine (IMI) and amitryptiline (AMI)) and secondary amines (desipramine (DES) and nortryptiline (NOR)) in water, methanol, and acetonitrile. We have determined the pKa values in those solvents and the variation of dissociation constants with the temperature. From these data, and applying the Van't Hoff equation, we have calculated the thermodynamic parameters deltaH and deltaS. The pKa values found in methanol for DES, NOR, IMI, and AMI were 10.80, 10.79, 10.38, and 10.33, respectively. On the other hand, in acetonitrile an opposite relation was found since the values were 20.60, 20.67, 20.74, and 20.81 for DES, NOR, IMI, and AMI. This is the reason why a migration order inversion is observed in NACE for these solvents. The thermodynamic parameters were evaluated and presented a tendency that can be correlated with that observed for pKa values.

  4. Immature granulocyte detection by the SE-9000 haematology analyser during pregnancy.

    PubMed

    Fernández-Suárez, A; Pascual, V T; Gimenez, M T F; Hernández, J F S

    2003-12-01

    The objective of this study was to determine the nature of the alarm for immature granulocytes appearing in haemograms from pregnant women, as detected by the immature cell information channel (IMI) of the SE-9000 automated haematology analyser. Of all tests run on pregnant women in a 4-month period (n = 698), the first 100 haemograms with immature granulocyte alarms (14.33%) were collected. Each of these samples was then stained with Wright-Giemsa stain. The following variables were also analysed: age of the mother, trimester and days of gestation, type of delivery, weight and sex of the baby, and Apgar score. Most pregnant women were in the third trimester of gestation (82%) when an alarm was noted on the IMI channel. Of the patients, 62% had normal deliveries. The most frequent complication was obstructed delivery (23%). Mean percentages by microscopic counts of band cells, metamyelocytes, and myelocytes were 2.99, 0.45, and 0.19%, respectively. There was a statistically significant correlation for all cell types between the SE-9000 and the manual count method. No association was observed between the presence of immature granulocytes and the clinical variables analysed. The SE-9000 analyser shows high sensitivity in the IMI channel for detection of immature forms.

  5. Effect of bromelain on milk yield, milk composition and mammary health in dairy goats.

    PubMed

    Contreras, A; Paape, M J; Miller, R H; Corrales, J C; Luengo, C; Sánchez, A

    2009-04-01

    A 7 month prospective cohort study was designed to determine if feeding bromelain to dairy goats influenced the MSCC, milk yield, milk composition and the incidence of IMI. Forty-four clinically normal goats from 2nd to 6th parities were studied. Daily bromelain dosage was 7.4 grams/animal (185-mg/Kg weight). Samples for diagnostic bacteriology were collected from each udder half every 2 weeks. Samples for MSCC and composition were obtained every 42 days. Milk yield was also recorded every 42 days. Bromelain affected milk protein and fat but not MSCC, milk yield or milk lactose. Bromelain did not decrease the MSCC in healthy goats. Milk protein and fat increased in the bromelain treated group (P < 0.01), which is important for dairymen because premiums are paid milk fat and protein content. No clinical mastitis was detected in the goats for the total study period and incidence rate of subclinical IMI was 5.7%. Relative risk was 1.50 (0.28 < RR < 8.12) which means that the bromelain had no significant effect on IMI (P > 0.05). In addition, the use of pineapple by-products could be especially important in tropical countries were pineapple waste seems to be a pollution problem.

  6. Examining the effect of intramammary infections with minor mastitis pathogens on the acquisition of new intramammary infections with major mastitis pathogens--a systematic review and meta-analysis.

    PubMed

    Reyher, K K; Haine, D; Dohoo, I R; Revie, C W

    2012-11-01

    Major mastitis pathogens such as Staphylococcus aureus, Streptococcus agalactiae, Streptococcus uberis, Streptococcus dysgalactiae, and the coliforms are usually considered more virulent and damaging to the udder than minor mastitis pathogens such as Corynebacterium bovis and coagulase-negative staphylococci (CNS). The current literature contains several studies detailing analyses with conflicting results as to whether intramammary infection (IMI) with the minor pathogens decreases, increases, or has no effect on the risk of a quarter acquiring a new intramammary infection (NIMI) with a major pathogen. To investigate the available scientific evidence regarding the effect of IMI with minor pathogens on the acquisition of NIMI with major pathogens, a systematic review and meta-analysis were conducted. The total extant English- and French-language literature in electronic databases was searched and all publications cited by relevant papers were investigated. Results from 68 studies were extracted from 38 relevant papers. Random-effects models were used to investigate the effects of CNS and C. bovis on acquisition of new IMI with any of the major pathogens, as well as individually for the minor pathogens and Staph. aureus. Significant heterogeneity among studies exists, some of which could be accounted for by using meta-regression. Overall, observational studies showed no effect, whereas challenge studies showed strong and significant protective effects, specifically when major pathogens were introduced into the mammary gland via methods bypassing the teat end. Underlying risk can account for several unmeasured factors, and studies with higher underlying risk found more protective effects of minor pathogens. Larger doses of challenge organisms reduced the protective effect of minor pathogens, and studies with more stringent diagnostic criteria for pathogen IMI identified less protection. Smaller studies (those utilizing fewer than 40 cows) also showed a greater protective effect than larger studies. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Formaldehyde exposure in U.S. industries from OSHA air sampling data.

    PubMed

    Lavoue, Jerome; Vincent, Raymond; Gerin, Michel

    2008-09-01

    National occupational exposure databanks have been cited as sources of exposure data for exposure surveillance and exposure assessment for occupational epidemiology. Formaldehyde exposure data recorded in the U.S Integrated Management Information System (IMIS) between 1979 and 2001 were collected to elaborate a multi-industry retrospective picture of formaldehyde exposures and to identify exposure determinants. Due to the database design, only detected personal measurement results (n = 5228) were analyzed with linear mixed-effect models, which explained 29% of the total variance. Short-term measurement results were higher than time-weighted average (TWA) data and decreased 18% per year until 1987 (TWA data 5% per year) and 5% per year (TWA data 4% per year) after that. Exposure varied across industries with maximal estimated TWA geometric means (GM) for 2001 in the reconstituted wood products, structural wood members, and wood dimension and flooring industries (GM = 0.20 mg/m(3). Highest short-term GMs estimated for 2001 were in the funeral service and crematory and reconstituted wood products industries (GM = 0.35 mg/m(3). Exposure levels in IMIS were marginally higher during nonprogrammed inspections compared with programmed inspections. An increasing exterior temperature tended to cause a decrease in exposure levels for cold temperatures (-5% per 5 degrees C for T < 15 degrees C) but caused an increase in exposure levels for warm temperatures (+15% per 5 degrees C for T >15 degrees C). Concentrations measured during the same inspection were correlated and varied differently across industries and sample type (TWA, short term). Sensitivity analyses using TOBIT regression suggested that the average bias caused by excluding non-detects is approximately 30%, being potentially higher for short-term data if many non-detects were actually short-term measurements. Although limited by availability of relevant exposure determinants and potential selection biases in IMIS, these results provide useful insight on formaldehyde occupational exposure in the United States in the last two decades. The authors recommend that more information on exposure determinants be recorded in IMIS.

  8. The combination of the entomopathogenic fungus Metarhizium anisopliae with the insecticide Imidacloprid increases virulence against the dengue vector Aedes aegypti (Diptera: Culicidae).

    PubMed

    Paula, Adriano R; Carolino, Aline T; Paula, Cátia O; Samuels, Richard I

    2011-01-25

    Dengue fever transmitted by the mosquito Aedes aegypti, is one of the most rapidly spreading insect borne diseases, stimulating the search for alternatives to current control measures. The dengue vector A. aegypti has received less attention than anophelene species, although more than 2.5 billion people are at risk of infection worldwide. Entomopathogenic fungi are emerging as potential candidates for the control of mosquitoes. Here we continue our studies on the pathogenicity of the entomopathogenic fungus Metarhizium anisopliae against adult A. aegypti females. With the aim of further reducing mean survival times of A. aegypti exposed to fungus impregnated surfaces, a sub-lethal concentration of the neonicotinoid insecticide Imidacloprid (IMI) was added to fungal suspensions. A sub-lethal concentration of IMI that did not significantly alter the daily survival rates or mean survival percentages of mosquitoes was identified to be 0.1 ppm. This sub-lethal concentration was combined with M. anisopliae conidia (1 × 10(9) conidia mL(-1)). Both the combined treatment and the conidia alone were able to reduce the survival of A. aegypti compared with untreated or IMI treated mosquitoes. Importantly, mosquito survival following exposure to the combined treatment for 6 and 12 hrs was significantly reduced when compared with mosquitoes exposed to conidia alone. This is the first time that a combination of an insecticide and an entomopathogenic fungus has been tested against A. aegypti. Firstly, the study showed the potential of IMI as an alternative to the currently employed pyrethroid adulticides. Secondly, as an alternative to applications of high concentrations of chemical insecticides, we suggest that adult A. aegypti could be controlled by surface application of entomopathogenic fungi and that the efficiency of these fungi could be increased by combining the fungi with ultra-low concentrations of insecticides, resulting in higher mortality following relatively short exposure times.

  9. The combination of the entomopathogenic fungus Metarhizium anisopliae with the insecticide Imidacloprid increases virulence against the dengue vector Aedes aegypti (Diptera: Culicidae)

    PubMed Central

    2011-01-01

    Background Dengue fever transmitted by the mosquito Aedes aegypti, is one of the most rapidly spreading insect borne diseases, stimulating the search for alternatives to current control measures. The dengue vector A. aegypti has received less attention than anophelene species, although more than 2.5 billion people are at risk of infection worldwide. Entomopathogenic fungi are emerging as potential candidates for the control of mosquitoes. Here we continue our studies on the pathogenicity of the entomopathogenic fungus Metarhizium anisopliae against adult A. aegypti females. With the aim of further reducing mean survival times of A. aegypti exposed to fungus impregnated surfaces, a sub-lethal concentration of the neonicotinoid insecticide Imidacloprid (IMI) was added to fungal suspensions. Results A sub-lethal concentration of IMI that did not significantly alter the daily survival rates or mean survival percentages of mosquitoes was identified to be 0.1 ppm. This sub-lethal concentration was combined with M. anisopliae conidia (1 × 109 conidia mL-1). Both the combined treatment and the conidia alone were able to reduce the survival of A. aegypti compared with untreated or IMI treated mosquitoes. Importantly, mosquito survival following exposure to the combined treatment for 6 and 12 hrs was significantly reduced when compared with mosquitoes exposed to conidia alone. Conclusions This is the first time that a combination of an insecticide and an entomopathogenic fungus has been tested against A. aegypti. Firstly, the study showed the potential of IMI as an alternative to the currently employed pyrethroid adulticides. Secondly, as an alternative to applications of high concentrations of chemical insecticides, we suggest that adult A. aegypti could be controlled by surface application of entomopathogenic fungi and that the efficiency of these fungi could be increased by combining the fungi with ultra-low concentrations of insecticides, resulting in higher mortality following relatively short exposure times. PMID:21266078

  10. Assessment of genetic diversity among barley cultivars and breeding lines adapted to the US Pacific Northwest, and its implications in breeding barley for imidazolinone-resistance.

    PubMed

    Rustgi, Sachin; Matanguihan, Janet; Mejías, Jaime H; Gemini, Richa; Brew-Appiah, Rhoda A T; Wen, Nuan; Osorio, Claudia; Ankrah, Nii; Murphy, Kevin M; von Wettstein, Diter

    2014-01-01

    Extensive application of imidazolinone (IMI) herbicides had a significant impact on barley productivity contributing to a continuous decline in its acreage over the last two decades. A possible solution to this problem is to transfer IMI-resistance from a recently characterized mutation in the 'Bob' barley AHAS (acetohydroxy acid synthase) gene to other food, feed and malting barley cultivars. We focused our efforts on transferring IMI-resistance to barley varieties adapted to the US Pacific Northwest (PNW), since it comprises ∼23% (335,000 ha) of the US agricultural land under barley production. To effectively breed for IMI-resistance, we studied the genetic diversity among 13 two-rowed spring barley cultivars/breeding-lines from the PNW using 61 microsatellite markers, and selected six barley genotypes that showed medium to high genetic dissimilarity with the 'Bob' AHAS mutant. The six selected genotypes were used to make 29-53 crosses with the AHAS mutant and a range of 358-471 F1 seeds were obtained. To make informed selection for the recovery of the recipient parent genome, the genetic location of the AHAS gene was determined and its genetic nature assessed. Large F2 populations ranging in size from 2158-2846 individuals were evaluated for herbicide resistance and seedling vigor. Based on the results, F3 lines from the six most vigorous F2 genotypes per cross combination were evaluated for their genetic background. A range of 20%-90% recovery of the recipient parent genome for the carrier chromosome was observed. An effort was made to determine the critical dose of herbicide to distinguish between heterozygotes and homozygotes for the mutant allele. Results suggested that the mutant can survive up to the 10× field recommended dose of herbicide, and the 8× and 10× herbicide doses can distinguish between the two AHAS mutant genotypes. Finally, implications of this research in sustaining barley productivity in the PNW are discussed.

  11. An observational cohort study on persistency of internal teat sealant residues in milk after calving in dairy cows.

    PubMed

    Kabera, Fidèle; Dufour, Simon; Keefe, Greg; Roy, Jean-Philippe

    2018-04-04

    Our objectives were to evaluate the prevalence of quarters with an observable internal teat sealant (ITS) plug at first milking following calving and investigate persistency of ITS residues in milk after calving. An observational cohort study was carried out on 557 quarters of 156 cows treated with ITS in 6 farms in Quebec, Canada. The presence of an ITS plug at first milking and ITS residues in milk at each milking were observed by producers. The effects of various factors on the odds of observing an ITS plug and persistency of ITS residues in milk were studied using generalized logistic mixed and generalized negative binomial mixed models, respectively. Milk samples were taken on the day before dry-off and on 2 occasions after calving for bacterial identification to detect intramammary infection (IMI) using bacteriological culture followed by MALDI-TOF identification. The association between the absence of an ITS plug and the presence of new IMI was assessed using a mixed logistic regression model. Internal teat sealant plugs after calving were more often observed in rear quarters and in quarters receiving ITS alone at drying-off versus antimicrobial and ITS. We observed an average (standard deviation) persistency of 4.0 d (2.3 d). When an ITS plug was still present at first milking (83% of quarters), the elimination of ITS residues in milk after calving was significantly longer (4.5 d, on average) compared with 1.2 d when an ITS plug was absent. In cows with an ITS plug at calving, we observed a higher number of days of excretion in older cows. When a plug could not be observed, rear quarters, older cows, and cows with a long dry period duration excreted ITS residues for a significantly longer period. The lack of a significant association between the absence of a plug and the odds of new IMI at calving suggests that despite the loss of the plug, cows were still protected against new IMI. Although we were able to highlight some statistically significant risk factors explaining persistency of ITS residues following calving, observed differences were often relatively small and, perhaps, not clinically relevant. In conclusion, an ITS plug was present until first milking after calving for 83% quarters, quarters without an ITS plug at first milking appeared to have been protected from new IMI, and ITS residues could be observed in milk up to 12 d in milk. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Ionothermal synthesis, characterization of a new layered gallium phosphate with an unusual heptamer SBU

    NASA Astrophysics Data System (ADS)

    Gao, Fan; Huang, Liangliang; Ma, Yike; Jiao, Shufei; Jiang, Yansong; Bi, Yanfeng

    2017-10-01

    A new layered gallium phosphate Ga3(PO4)4(C2N2H8)·(H2C2N2H8)2·Cl (compound 1), has been ionothermally synthesized in the presence of deep eutectic solvent (DES) comprising mixtures of choline chloride and 2-imidazolidone (IMI). Single-crystal X-ray diffraction analysis reveals that compound 1 shows 2D layered framework with 10-ring windows, which is constructed from unusual heptamer second building units (SBUs). The ethylenediamine (en) units deriving from the decomposition of IMI, play a dual role as bidentate ligands coordinated with 6-fold coordinate gallium atoms and the templates. Additionally, compound 1 shows photoluminescence property in solid state at room temperature.

  13. Assessment of Biopsychosocial Complexity and Health Care Needs: Measurement Properties of the INTERMED Self-Assessment Version.

    PubMed

    van Reedt Dortland, Arianne K B; Peters, Lilian L; Boenink, Annette D; Smit, Jan H; Slaets, Joris P J; Hoogendoorn, Adriaan W; Joos, Andreas; Latour, Corine H M; Stiefel, Friedrich; Burrus, Cyrille; Guitteny-Collas, Marie; Ferrari, Silvia

    2017-05-01

    The INTERMED Self-Assessment questionnaire (IMSA) was developed as an alternative to the observer-rated INTERMED (IM) to assess biopsychosocial complexity and health care needs. We studied feasibility, reliability, and validity of the IMSA within a large and heterogeneous international sample of adult hospital inpatients and outpatients as well as its predictive value for health care use (HCU) and quality of life (QoL). A total of 850 participants aged 17 to 90 years from five countries completed the IMSA and were evaluated with the IM. The following measurement properties were determined: feasibility by percentages of missing values; reliability by Cronbach α; interrater agreement by intraclass correlation coefficients; convergent validity of IMSA scores with mental health (Short Form 36 emotional well-being subscale and Hospital Anxiety and Depression Scale), medical health (Cumulative Illness Rating Scale) and QoL (Euroqol-5D) by Spearman rank correlations; and predictive validity of IMSA scores with HCU and QoL by (generalized) linear mixed models. Feasibility, face validity, and reliability (Cronbach α = 0.80) were satisfactory. Intraclass correlation coefficient between IMSA and IM total scores was .78 (95% CI = .75-.81). Correlations of the IMSA with the Short Form 36, Hospital Anxiety and Depression Scale, Cumulative Illness Rating Scale, and Euroqol-5D (convergent validity) were -.65, .15, .28, and -.59, respectively. The IMSA significantly predicted QoL and also HCU (emergency department visits, hospitalization, outpatient visits, and diagnostic examinations) after 3- and 6-month follow-up. Results were comparable between hospital sites, inpatients and outpatients, as well as age groups. The IMSA is a generic and time-efficient method to assess biopsychosocial complexity and to provide guidance for multidisciplinary care trajectories in adult patients, with good reliability and validity across different cultures.

  14. The stomach, cholecystokinin, and satiety.

    PubMed

    McHugh, P R; Moran, T H

    1986-04-01

    The stomach of the rhesus monkey empties liquids in a fashion that varies with the character of the solutions. Physiological saline empties exponentially. Glucose solutions empty biphasically--rapidly for the first minutes, then slowly and proportionately to glucose concentration to deliver glucose calories through the pylorus at a regulated rate (0.4 kcal/min). This prolonged and regulated second phase of gastric emptying depends on intestinal inhibition of the stomach. Cholecystokinin (CCK), a hormone released by food in the intestine, is an inhibitor of gastric emptying. In vitro receptor autoradiography demonstrates CCK receptors to be clustered on the circular muscle of the pylorus. Exogenous CCK, in doses that inhibit gastric emptying, will reduce food intake only if combined with an infusion of saline in the stomach. These observations indicate how gastric distension can be a means for provoking satiety. The variably sustained distension produced by the stomach's slow, calorically regulated emptying could prolong intermeal intervals and thus permit high-calorie meals to inhibit further caloric intake over time. CCK, by directly inhibiting gastric emptying during a meal, could promote gastric distension and so restrict the duration and size of individual meals.

  15. Greener Alternatives to Expedient Synthesis of Heterocycles and Nanomaterial

    EPA Science Inventory

    A brief account of reactions involving microwave (MW) exposure of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds [1] from in situ generated reactive interm...

  16. Bovine mastitis outbreak in Japan caused by methicillin-resistant Staphylococcus aureus New York/Japan clone.

    PubMed

    Hata, Eiji

    2016-05-01

    Many methicillin-resistant Staphylococcus aureus (MRSA) strains are multidrug-resistant; consequently, infectious diseases involving MRSA are recognized as troublesome diseases not only in human health care but also in animal health care. A bovine mastitis case caused by MRSA isolates of the New York/Japan clone (NJC), which occurred in Japan in 2005, was monitored in the current study. Isolates of the NJC are typical of hospital-acquired MRSA in Japan. The genetic backgrounds of these strains differ from those of bovine-associated S. aureus, which are typically of clonal complex (CC)97, CC705, and CC133. Moreover, the NJC isolates in this bovine outbreak possessed a β-hemolysin-converting bacteriophage and an immune evasion cluster, as found in the NJC isolates from humans, so it is possible that this clone was introduced into the dairy herd by a human carrier. Most bovine intramammary infections (IMIs) caused by the NJC isolates in our study were asymptomatic, and obvious clinical signs were recognized in only the first 3 infected cows. Of a total of 78 cows, 31 cows were MRSA carriers, and these carrier cows were detected by testing the milk of all lactating cows at 1-month intervals. These S. aureus carrier cows were culled or the infected quarter was dried off and no longer milked. Both IMI and mastitis caused by MRSA were completely eradicated after 5 months. Genotyping data suggested that exchanging of the staphylococcal cassette chromosome mec (the determining factor in methicillin resistance) occurred easily between MRSA and methicillin-sensitive S. aureus in the udders of carrier cows. This case study demonstrates an effective procedure against the spread of MRSA in a dairy herd, and highlights the risk of emergence of new MRSA strains in a dairy herd. © 2016 The Author(s).

  17. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants.

    PubMed

    Marr, Kieren A; Crippa, Fulvio; Leisenring, Wendy; Hoyle, Maggie; Boeckh, Michael; Balajee, S Arunmozhi; Nichols, W Garrett; Musher, Benjamin; Corey, Lawrence

    2004-02-15

    Prophylactic fluconazole prevents candidiasis; however, this drug has no activity against molds. We performed a randomized trial to determine whether prophylactic itraconazole prevents invasive mold infections (IMIs). A total of 304 patients receiving allogeneic stem cell transplants (SCT) were randomized to receive fluconazole (400 mg/d) or itraconazole (oral solution 2.5 mg/kg 3 times daily, or intravenous 200 mg daily) for 180 days after SC transplantation, or until 4 weeks after discontinuation of graft-versus-host disease (GVHD) therapy. Proven or probable invasive fungal infections (IFI) were evaluated by intent-to-treat and "on-treatment" analyses. More patients in the itraconazole arm developed hepatotoxicities, and more patients were discontinued from itraconazole because of toxicities or gastrointestinal (GI) intolerance (36% versus 16%, P <.001). Intent-to-treat analysis demonstrated no difference in the incidence of IFI during the intended study period (fluconazole 16% versus itraconazole 13%, P =.46); however, fewer patients in the itraconazole arm developed IFI on treatment (fluconazole 15% versus itraconazole 7%, P =.03). Itraconazole provided better protection against IMI (fluconazole 12% versus itraconazole 5%, P =.03), but similar protection against candidiasis (3% versus 2%, P =.69). There was no difference in overall or fungal-free survival. Itraconazole appears to prevent IMI in the subset of patients who tolerate the drug; however, toxicities and poor tolerability limit its success as prophylactic therapy.

  18. Risk of Progression and Survival in Multiple Myeloma Relapsing After Therapy with IMiDs and Bortezomib: A Multicenter International Myeloma Working Group Study

    PubMed Central

    Kumar, Shaji; Lee, Jae Hoon; Lahuerta, Juan J.; Morgan, Gareth; Richardson, Paul G.; Crowley, John; Haessler, Jeff; Feather, John; Hoering, Antje; Moreau, Philippe; LeLeu, Xavier; Hullin, Cyrille; Klein, Saskia K.; Sonneveld, Pieter; Siegel, David; Bladé, Joan; Goldschmidt, Hartmut; Jagannath, Sundar; San Miguel, Jesus; Orlowski, Robert; Palumbo, Antonio; Sezer, Orhan; Durie, Brian G.M.

    2014-01-01

    Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed, refractory, or ineligible, to an IMiD (Immunomodulatory Drug), with measurable disease and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (51%) including >=partial response in 69 (38%). The median overall survival and event free survival from T0 were 9 and 5 months respectively. This study confirms the poor outcome once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. PMID:21799510

  19. Creating neighbourhood groupings based on built environment features to facilitate health promotion activities.

    PubMed

    Schopflocher, Donald; VanSpronsen, Eric; Spence, John C; Vallianatos, Helen; Raine, Kim D; Plotnikoff, Ronald C; Nykiforuk, Candace I J

    2012-07-26

    Detailed assessments of the built environment often resist data reduction and summarization. This project sought to develop a method of reducing built environment data to an extent that they can be effectively communicated to researchers and community stakeholders. We aim to help in an understanding of how these data can be used to create neighbourhood groupings based on built environment characteristics and how the process of discussing these neighbourhoods with community stakeholders can result in the development of community-informed health promotion interventions. We used the Irvine Minnesota Inventory (IMI) to assess 296 segments of a semi-rural community in Alberta. Expert raters "created" neighbourhoods by examining the data. Then, a consensus grouping was developed using cluster analysis, and the number of IMI variables to characterize the neighbourhoods was reduced by multiple discriminant function analysis. The 296 segments were reduced to a consensus set of 10 neighbourhoods, which could be separated from each other by 9 functions constructed from 24 IMI variables. Biplots of these functions were an effective means of summarizing and presenting the results of the community assessment, and stimulated community action. It is possible to use principled quantitative methods to reduce large amounts of information about the built environment into meaningful summaries. These summaries, or built environment neighbourhoods, were useful in catalyzing action with community stakeholders and led to the development of health-promoting built environment interventions.

  20. On the factorial and construct validity of the Intrinsic Motivation Inventory: conceptual and operational concerns.

    PubMed

    Markland, D; Hardy, L

    1997-03-01

    The Intrinsic Motivation Inventory (IMI) has been gaining acceptance in the sport and exercise domain since the publication of research by McAuley, Duncan, and Tammen (1989) and McAuley, Wraith, and Duncan (1991), which reported confirmatory support for the factorial validity of a hierarchical model of intrinsic motivation. Authors of the present study argue that the results of these studies did not conclusively support the hierarchical model and that the model did not accurately reflect the tenets of cognitive evaluation theory (Deci & Ryan, 1985) from which the IMI is drawn. It is also argued that a measure of perceived locus of causality is required to model intrinsic motivation properly. The development of a perceived locus of causality for exercise scale is described, and alternative models, in which perceived competence and perceived locus of causality are held to have causal influences on intrinsic motivation, are compared with an oblique confirmatory factor analytic model in which the constructs are held at the same conceptual level. Structural equation modeling showed support for a causal model in which perceived locus of causality mediates the effects of perceived competence on pressure-tension, interest-enjoyment, and effort-importance. It is argued that conceptual and operational problems with the IMI, as currently used, should be addressed before it becomes established as the instrument of choice for assessing levels of intrinsic motivation.

  1. Circadian and ultradian components of hunger in human non-homeostatic meal-to-meal eating.

    PubMed

    Wuorinen, Elizabeth C; Borer, Katarina T

    2013-10-02

    A unifying physiological explanation of the urge to initiate eating is still not available as human hunger in meal-to-meal eating may not be under homeostatic control. We hypothesized that a central circadian and a gastrointestinal ultradian timing mechanism coordinate non-deprivation meal-to-meal eating. We examined hunger as a function of time of day, inter-meal (IM) energy expenditure (EE), and concentrations of proposed hunger-controlling hormones ghrelin, leptin, and insulin. In two crossover studies, 10 postmenopausal women, BMI 23-26 kg/m(2) engaged in exercise (EX) and sedentary (SED) trials. Weight maintenance meals were provided at 6h intervals with an ad libitum meal at 13 h in study 1 and 21 h snack in study 2. EE during IM intervals was measured by indirect calorimetry and included EX EE of 801 kcal in study 1, and 766-1,051 kcal in study 2. Hunger was assessed with a visual analog scale and blood was collected for hormonal determination. Hunger displayed a circadian variation with acrophase at 13 and 19 h and was unrelated to preceding EE. Hunger was suppressed by EX between 10 and 16 h and bore no relationship to either EE during preceding IM intervals or changes in leptin, insulin, and ghrelin; however leptin reflected IM energy changes and ghrelin and insulin, prandial events. During non-deprivation meal-to-meal eating, hunger appears to be under non-homeostatic central circadian control as it is unrelated to EE preceding meals or concentrations of proposed appetite-controlling hormones. Gastrointestinal meal processing appears to intermittently suppress this control and entrain an ultradian hunger pattern. © 2013 Elsevier Inc. All rights reserved.

  2. Contemporary Theories of Depression: Critique and Comparison

    ERIC Educational Resources Information Center

    Blaney, Paul H.

    1977-01-01

    Three theoretical viewpoints have dominated the recent empirically oriented literature on depression: Beck's cognitive view, Seligman's helplessness model, and Lewinsohn's theory implicating a low rate of response-contingent reinforcement. Here each theory is evaluated individually interms of its empirical support and adequacy as a theory and all…

  3. Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.

    PubMed

    Arruda, A G; Godden, S; Rapnicki, P; Gorden, P; Timms, L; Aly, S S; Lehenbauer, T W; Champagne, J

    2013-07-01

    The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93.3%, SP=92.6%, and TM=94.0%] and secondary analysis showed no effect of treatment on risk for presence of an IMI at 0 to 6 DIM (LSM: QT=16.5%, SP=14.1%, and TM=16.0%), risk for development of a new IMI between dry-off and 0 to 6 DIM (LSM: QT=14.8%, SP=12.3%, and TM=14.2%), or risk of experiencing a clinical mastitis event between calving and 100 DIM (LSM: QT=5.3%, SP=3.8%, and TM=4.1%). In conclusion, no difference was observed in efficacy among the 3 products evaluated when assessing the aforementioned quarter-level outcomes. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Pre-transplantation novel agent induction predicts progression-free survival for patients with immunoglobulin light-chain amyloidosis undergoing high-dose melphalan and autologous stem cell transplantation.

    PubMed

    Cowan, Andrew J; Klippel, Zandra K; Stevenson, Philip A; Hyun, Teresa S; Tuazon, Sherilyn; Becker, Pamela S; Green, Damian J; Holmberg, Leona A; Coffey, David G; Gopal, Ajay K; Libby, Edward N

    2016-12-01

    High-dose melphalan and autologous stem cell transplantation (HDM/SCT) is an effective treatment modality for immunoglobulin light-chain (AL) amyloidosis; however, its application remains restricted to patients with good performance status and limited organ involvement. In recent years, the paradigm for AL amyloidosis has changed with the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). We hypothesized that use of novel agent induction regimens has improved outcomes for patients with AL amyloidosis undergoing HDM/SCT at our center. All patients with AL amyloidosis, age ≥18 years who underwent HDM/SCT between 2001 and 2014 at the Fred Hutchinson Cancer Research Center and University of Washington Medical Center were included in this study. Any regimen administered within 6 months prior to HDM/SCT including an IMiD or a PI was considered a novel induction regimen. Use of induction regimen was evaluated in a Cox proportional hazard model for association with progression-free survival (PFS) and overall survival (OS). Forty-five patients with AL amyloidosis underwent HDM/SCT. The median age was 57.2 years (range 39-74.4), 15 (33.3%) were women. The median number of organs involved was 2 (range 1-5), with 20 patients having only 1 (44.4%), 10 patients having 2 (22.2%), and 15 patients (33.3%) having ≥ 3 organs involved. Novel agent induction regimens were used prior to HDM/SCT in 21 patients (46.7%); these comprised PI in 13/21 (57.1%), IMiD alone in 6/21 (28.6%), PI and cyclophosphamide (CyBorD) in 3/21 (14.3%), and IMiD and PI in 3/21 (14.3%). Use of a novel agent induction regimen was associated with improved, but not OS. The 3-year PFS for patients who received a novel agent induction was 79%, while for those who did not was 53% (hazard ratio [HR] = 0.317, p = 0.048). The 3-year OS for patients who received novel agent induction regimens was 95%, while for those who did not was 71% (HR = 0.454, p = 0.247). Our data suggest that use of a novel agent induction regimen including an IMiD or PI prior to HDM/SCT for patients with AL amyloidosis could improve outcomes, with improvement in PFS. Although these results are limited by sample size and lack of randomization, these results support possible further investigation of novel agent induction regimens in the context of a prospective clinical trial.

  5. Thalidomide

    MedlinePlus

    ... biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacology & Therapeutics. 2012;136:56. Thalomid (prescribing information). Summit, N. ... Behcet disease. In: Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 4th ed. Philadelphia, Pa.: Saunders Elsevier; 2014. ...

  6. Decreased insulin sensitivity due to continuous nutrient administration in neonatal pigs

    USDA-ARS?s Scientific Manuscript database

    Chronic TPN compared to intermittent formula feeding has been shown to induce hepatic insulin resistance and steatosis in neonatal pigs. We hypothesized that the route of feeding (IV vs. enteral) rather than the nature of the diet (elemental vs polymeric) or the feeding regimen (continuous vs interm...

  7. Gaps Between What We Measure and What We Want to Know to Value Streams

    EPA Science Inventory

    We have found the concept “Final Ecosystem Goods and Services” (FEGS) useful in linking ecosystems and human well-being. We define FEGS as ecological features people perceive to be directly relevant to their welfare, as opposed to the larger set of essential intermed...

  8. Lessons Learned for Recruiting and Retaining Native Hawaiians in the Geosciences

    NASA Astrophysics Data System (ADS)

    Gibson, B. A.; Brock, L.; Levine, R.; Spencer, L.; Wai, B.; Puniwai, N.

    2008-12-01

    Many Native Hawaiian and Pacific Island (NHPI) college students are unaware of the majors or career possibilities within geoscience disciplines. This notably can be seen by the low number of NHPI students who graduate with a bachelor's degree in an ocean or Earth science-related field within the University of Hawaii (UH) System. To help address this disparity, the Ka'Imi'Ike Program, which is funded through the Opportunities for Enhancing Diversity in the Geosciences (OEDG) Program at NSF, was started at the University of Hawaii at Manoa to attract and support NHPI students in the geosciences. A key component of the program is the recruiting of NHPI students to disciplines in the geosciences through linking geoscience concepts with their culture and community. This includes a 3-week Explorations in the Geosciences summer institute that introduces incoming freshmen and current UH sophomores to the earth, weather, and ocean sciences via hands-on field and lab experiences. Ka'Imi'Ike also provides limited support for current geoscience majors through scholarships and internship opportunities. Results from student journals and pre- and post- questionnaires given to students during the summer institute have shown the program to be successful in increasing student interest and knowledge of the geoscience disciplines. Demonstrating the links between scientific thought and NHPI culture has been crucial to peaking the students' interest in the geosciences. The results also show that there is a need to include more specifics related to local career options, especially information that can be shared with the students' family and community as our data show that parents play a formidable role in the career path a student chooses. Moreover, in order to provide a more contiguous pipeline of support for NHPI students, Ka'Imi'Ike is beginning to network its students from the summer institute to other programs, such as the C-MORE Scholars Program, which offer undergraduate research experiences in the ocean and earth sciences. Though the Ka'Imi'Ike Program has been quite successful in facilitating NHPI participation in undergraduate research projects, the program is continually evolving by seeking and developing cutting edge approaches to strengthen its recruitment of NHPI into geoscience majors and careers.

  9. Cost effectiveness of ciprofloxacin plus metronidazole versus imipenem-cilastatin in the treatment of intra-abdominal infections.

    PubMed

    Walters, D J; Solomkin, J S; Paladino, J A

    1999-11-01

    To compare the cost effectiveness of sequential intravenous (i.v.) to oral ciprofloxacin plus metronidazole (CIP/MTZ i.v./PO) with that of i.v. ciprofloxacin plus i.v. metronidazole (CIP/MTZ i.v.) and i.v. imipenem-cilastatin (IMI i.v.) in patients with intra-abdominal infections. Patients enrolled in a double-blind randomised clinical trial were eligible for inclusion into this cost-effectiveness analysis. Decision analysis was used to characterise the economic outcomes between groups and provide a structure upon which to base the sensitivity analyses. 1996 cost values were used throughout. The economic perspective of the analysis was that of a hospital provider. Among 446 economically evaluable patients, 176 could be switched from i.v. to oral administration. The 51 patients randomised to CIP/MTZ i.v./PO who received active oral therapy had a success rate of 98%, mean duration of therapy of 9.1 days and mean cost of $US7678. There were 125 patients randomized to either CIP/MTZ i.v. or IMI i.v. who received oral placebo while continuing on active i.v. antibacterials; their success rate was 94%, mean duration of therapy was 10.1 days and mean cost was $US8774 (p = 0.029 vs CIP/MTZ i.v./PO). Of the 270 patients who were unable to receive oral administration, 97 received IMI i.v. and had a success rate of 75%, mean duration of therapy of 13.8 days and a mean cost of $US12,418, and 173 received CIP/MTZ i.v. and had a success rate of 77%, mean duration of therapy of 13.4 days and mean cost of $US12,219 (p = 0.26 vs IMI i.v.). In patients able to receive oral therapy, sequential i.v. to oral treatment with ciprofloxacin plus metronidazole was cost effective compared with full i.v. courses of ciprofloxacin plus metronidazole or imipenem-cilastatin. In patients unable to receive oral therapy, no difference in mean cost was found between i.v. imipenem-cilastatin or i.v. ciprofloxacin plus i.v. metronidazole.

  10. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine.

    PubMed

    Guan, Xi-ting; Shao, Feng; Xie, Xi; Chen, Lin; Wang, Weiwen

    2014-09-01

    Aspirin (ASP) is the most commonly used non-steroidal anti-inflammatory drug in the world. Recent clinical and preclinical evidence suggests that ASP may also exert psychoactive effects. It remains unclear whether ASP has antidepressant-like activity, and any molecular mechanisms underlying such activity have yet to be elucidated. Using the forced swimming test (FST), a well-established animal model of depression widely used to screen potential antidepressants in rodents, we investigated the effects of subacute treatment with ASP (0, 6, 12, 25, and 50mg/kg, i.p.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in rats, in comparison to the clinical antidepressants imipramine (IMI) and fluoxetine (FLU). Serum levels of corticosterone, pro-inflammatory cytokine interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. ASP dose-dependently decreased immobility in the FST, without altering the locomotor activity in the open-field test. The inhibitory effects of higher doses (25 and 50mg/kg) of ASP on immobility were similar to that of FLU and IMI at a dose of 10mg/kg. In addition, the levels of corticosterone, IL-6, and TNF-α in peripheral blood were significantly increased after the FST exposure. IMI, but not FLU and ASP at any dose tested, significantly attenuated corticosterone responses in the FST. Both FLU and IMI treatment reduced the increase of IL-6 and TNF-α levels following the FST exposure. ASP dose-dependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on IL-6 and TNF-α levels at higher doses (25 and 50mg/kg) than the lowest dose of ASP (6 mg/kg). In all, these results indicate that ASP treatment dose-dependently decreased the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of ASP might be involved in the antidepressant-like effect. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The effect of intracerebroventricular allopregnanolone on depressive-like behaviors of rats selectively bred for high and low immobility in the forced swim test.

    PubMed

    Almeida, Felipe Borges; Fonseca, Alan Rios; Heidrich, Núbia; Nin, Maurício Schüler; Barros, Helena Maria Tannhauser

    2018-06-12

    Depression is a highly incapacitating disorder known to have a multifactorial etiology, including a hereditary genetic background. The neurosteroid allopregnanolone (ALLO) is a positive allosteric modulator of the GABA A receptor and has been shown to have an antidepressant-like effect in animals. This study aimed to assess the behavioral effect of ALLO in animals with different backgrounds of depressive-like activity. An initial population (F0) of male and female Wistar rats was screened for immobility behavior utilizing the Forced Swim Test (FST). Rats with extreme immobility scores were selected for either the High Immobility (HI) group or the Low Immobility (LI) group for breeding, giving origin to the subsequent generations F1 and F2. Guide cannulas were implanted in the lateral ventricle of F2 males for intracerebroventricular infusions of 5 μg/rat of ALLO, 5 μg/rat of imipramine (IMI) or vehicle (CTR), which occurred 24, 5 and 1 h prior to the test session of the drug FST. In the pre-drug FST, a statistically significant difference was observed between the immobility scores from the HI and LI groups of F2 rats. HI rats from F2 also showed significantly higher immobility time when compared to F0. In these HI animals, both IMI and ALLO significantly reduced immobility when compared to the CTR group. IMI-treated rats also showed lower immobility than the ALLO group. In the LI rats, no difference in immobility was found between treatments. In conclusion, two strains of rats with significantly different immobility profiles in the FST were obtained in a relatively short time, after only two generations. Infusions of both ALLO and IMI showed a strain-dependent antidepressant-like effect, being detected in the HI animals but not in the LI animals, which is in line with the clinical understanding that antidepressants have higher efficacy in more severe forms of depression. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Development of WAIS-III General Ability Index Minus WMS-III memory discrepancy scores.

    PubMed

    Lange, Rael T; Chelune, Gordon J; Tulsky, David S

    2006-09-01

    Analysis of the discrepancy between intellectual functioning and memory ability has received some support as a useful means for evaluating memory impairment. In recent additions to Wechlser scale interpretation, the WAIS-III General Ability Index (GAI) and the WMS-III Delayed Memory Index (DMI) were developed. The purpose of this investigation is to develop base rate data for GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores using data from the WAIS-III/WMS-III standardization sample (weighted N = 1250). Base rate tables were developed using the predicted-difference method and two simple-difference methods (i.e., stratified and non-stratified). These tables provide valuable data for clinical reference purposes to determine the frequency of GAI-IMI, GAI-GMI, and GAI-DMI discrepancy scores in the WAIS-III/WMS-III standardization sample.

  13. Phosphatidylserine-exposing cells contribute to the hypercoagulable state in patients with multiple myeloma.

    PubMed

    Guo, Li; Tong, Dongxia; Yu, Muxin; Zhang, Yan; Li, Tao; Wang, Chunxu; Zhou, Peng; Jin, Jiaqi; Li, Baorong; Liu, Yingmiao; Liu, Ruipeng; Novakovic, Valerie A; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Bi, Yayan; Zhou, Jin; Shi, Jialan

    2018-06-01

    Multiple myeloma (MM) is characterized by an increased incidence of thromboembolic events, particularly when treated with immunomodulatory drugs (IMiDs) in combination with dexamethasone. The optimal prophylactic strategy to prevent the hypercoagulable state of patients with MM is still debated. The aim of the current study was to investigate the definitive role of phosphatidylserine (PS) in supporting procoagulant activity (PCA) in patients with MM. Patients with MM (n=20) and healthy subjects (n=15) were recruited for the present study. PS analyses were performed by flow cytometry and confocal microscopy. The PCA was evaluated by clotting time, purified coagulation complex assays and fibrin production assays. The percentage of PS+ blood cells was significantly higher in patients with MM than in healthy subjects. Additionally, the patient serum induced more PS exposure on endothelial cells (ECs) in vitro than serum from healthy subjects. Isolated blood cells from patients with MM and ECs cultured with patient serum in vitro demonstrated significantly shortened coagulation time, greatly intrinsic/extrinsic factor Xa generation and increased thrombin formation. In addition, the levels of PS+ erythrocytes, platelets, leukocytes, and ECs incubated with IMiDs and dexamethasone were higher than with IMiDs alone. The findings support the hypothesis that increased PS exposure on blood cells and ECs participates in the hypercoagulable state in patients with MM. Thus, blocking PS may be a novel therapeutic target for the prevention of thrombosis in these patients.

  14. The Far Ultraviolet (FUV) auroral imager for the Inner Magnetospheric Imager (IMI) mission: Options

    NASA Technical Reports Server (NTRS)

    Wilson, Gordon R.

    1993-01-01

    The change from an intermediate mission (cost ceiling of $300 million) to a solar-terrestrial probe class mission (cost ceiling of $150 million) will require some major changes in the configuration of the IMI mission. One option being considered is to move to a small spin-stabilized spacecraft (with no despun platform) which could be launched with a smaller Taurus or Conestoga class booster. Such a change in spacecraft type would not present any fundamental problems (other than restrictions on mass and power) for the He plus 304 A plasmasphere imager, the high and low energy neutral atom imagers, and the geocoronal imager, but would present a challenge for the FUV auroral imager since the original plan called for this instrument to operate from a despun platform. Since the FUV instrument is part of the core payload it cannot be dropped from the instrument complement without jeopardizing the science goals of the mission. A way must be found to keep this instrument and to allow it to accomplish most, if not all, of its science objectives. One of the subjects discussed are options for building an FUV instrument for a spinning spacecraft. Since a number of spinning spacecraft have carried auroral imagers, a range of techniques exists. In addition, the option of flying the FUV imager on a separate micro-satellite launched with the main IMI spacecraft or with a separate pegasus launch, was considered and is discussed.

  15. Defining standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to mastitis pathogens.

    PubMed

    Schukken, Y H; Rauch, B J; Morelli, J

    2013-04-01

    The objective of this paper was to define standardized protocols for determining the efficacy of a postmilking teat disinfectant following experimental exposure of teats to both Staphylococcus aureus and Streptococcus agalactiae. The standardized protocols describe the selection of cows and herds and define the critical points in performing experimental exposure, performing bacterial culture, evaluating the culture results, and finally performing statistical analyses and reporting of the results. The protocols define both negative control and positive control trials. For negative control trials, the protocol states that an efficacy of reducing new intramammary infections (IMI) of at least 40% is required for a teat disinfectant to be considered effective. For positive control trials, noninferiority to a control disinfectant with a published efficacy of reducing new IMI of at least 70% is required. Sample sizes for both negative and positive control trials are calculated. Positive control trials are expected to require a large trial size. Statistical analysis methods are defined and, in the proposed methods, the rate of IMI may be analyzed using generalized linear mixed models. The efficacy of the test product can be evaluated while controlling for important covariates and confounders in the trial. Finally, standards for reporting are defined and reporting considerations are discussed. The use of the defined protocol is shown through presentation of the results of a recent trial of a test product against a negative control. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Higher levels of intrinsic motivation are related to higher levels of class performance for male but not female students.

    PubMed

    Cortright, Ronald N; Lujan, Heidi L; Blumberg, Amanda J; Cox, Julie H; DiCarlo, Stephen E

    2013-09-01

    Our students are naturally curious, with powerful intrinsic motives to understand their world. Accordingly, we, as teachers, must capitalize on this inherently active and curious nature so that learning becomes a lifelong activity where students take initiative for learning, are skilled in learning, and want to learn new things. Achieving this goal requires an understanding of student attitudes, beliefs, characteristics, and motivations. To achieve this goal, we administered the intrinsic motivation inventory (IMI) to assess our students' interest and enjoyment, perceived choice, and perceived competence while taking our undergraduate exercise physiology class (46 students; 20 female students and 26 male students). The interest and enjoyment subscale is considered the self-reported measure of intrinsic motivation. The perceived choice and perceived competence concepts are theorized to be positive predictors of both self-reported and behavioral measures of intrinsic motivation. Our results documented a significant increase in course grade with an increase in survey score for the interest and enjoyment subscale of the IMI when female and male students were combined. Specifically, each increase in survey score for the interest and enjoyment subscale of the IMI was associated with a significant (P < 0.05) increase of 3.9% in course grade. However, the increase in survey score was associated with a significantly greater (P < 0.05) increase in course grade for male (6.1%) compared with female (0.3%) students. These results have implications for both classroom practice and educational reform policies.

  17. Imi Ho'ola: an educational model for disadvantaged students at the University of Hawai''i School of Medicine.

    PubMed

    Judd, Nanette L K; Sakamoto, Karen K; Hishinuma, Earl S; DeCambra, Chessa; Malate, Agnes R

    2007-03-01

    This paper describes an educational model that provides opportunities in medicine to students from disadvantaged backgrounds that have a commitment to serve in areas of need, and it presents guidelines on how this model could be adapted to various settings. From 1973 to 2002, the Imi Ho'ola Program (Hawaiian for "Those Who Seek to Heal") of the University of Hawai'i John A. Burns School of Medicine (JABSOM) has provided opportunities in medicine to 379 students from disadvantaged backgrounds. In 1995-1996, Imi Ho'ola underwent a transformation from a pre-medical enrichment program to a post-baccalaureate program that included provisional acceptance and financial support into JABSOM for students who successfully completed the program. As a result, the acceptance rate increased from 47.6% to 98.0%. In addition to provisional acceptance to JABSOM and financial support, the program's educational model incorporates five components, the key factors of the program's success: 1) JABSOM commitment and the institutionalization of the program; 2) emphasis placed on a comprehensive approach and the implementation of a curriculum and learning process that are aligned with JABSOM curricula; 3) faculty and staff who support the instructional methodology and work as a team to address students' needs; 4) assessment of students and systematic feedback regarding individualized education plans and academic and non-academic progress; and 5) a positive learning environment for students. Guidelines are provided in this article for consideration in adapting this educational model to other academic settings.

  18. Temporal Changes in Aqu/C60 Physical-Chemical, Deposition, and Transport Characteristics in Aqueous Systems

    EPA Science Inventory

    Little is known about how temporal changes in the physical–chemical properties of C60 aggregates formed in aqueous systems (termed aqu/C60) can impact transport pathways contributing to ecological exposures. In this study three aqu/C60 suspensions of short-term (100 days), interm...

  19. Ionomic characterization of maize kernels in the Intermated B73 x Mo17 (IBM) population

    USDA-ARS?s Scientific Manuscript database

    Dietary mineral deficiencies affect nearly half of the people on our planet, largely due to poverty. Many people do not receive adequate calcium, iron, zinc, and other mineral nutrients from the food they grow or purchase. These kinds of dietary deficiencies create both acute and chronic health prob...

  20. Randomized noninferiority study evaluating the efficacy of 2 commercial dry cow mastitis formulations.

    PubMed

    Johnson, A P; Godden, S M; Royster, E; Zuidhof, S; Miller, B; Sorg, J

    2016-01-01

    The study objective was to compare the efficacy of 2 commercial dry cow mastitis formulations containing cloxacillin benzathine or ceftiofur hydrochloride. Quarter-level outcomes included prevalence of intramammary infection (IMI) postcalving, risk for cure of preexisting infections, risk for acquiring a new IMI during the dry period, and risk for clinical mastitis between dry off and 100 d in milk (DIM). Cow-level outcomes included the risk for clinical mastitis and the risk for removal from the herd between dry off and 100 DIM, as well as Dairy Herd Improvement Association (DHIA) test-day milk component and production measures between calving and 100 DIM. A total of 799 cows from 4 Wisconsin dairy herds were enrolled at dry off and randomized to 1 of the 2 commercial dry cow therapy (DCT) treatments: cloxacillin benzathine (DC; n=401) or ceftiofur hydrochloride (SM; n=398). Aseptic quarter milk samples were collected for routine bacteriological culture before DCT at dry off and again at 0 to 10 DIM. Data describing clinical mastitis cases and DHIA test-day results were retrieved from on-farm electronic records. The overall crude quarter-level prevalence of IMI at dry off was 34.7% and was not different between treatment groups. Ninety-six percent of infections at dry off were of gram-positive organisms, with coagulase-negative Staphylococcus and Aerococcus spp. isolated most frequently. Mixed logistic regression analysis showed no difference between treatments as to the risk for presence of IMI at 0 to 10 DIM (DC=22.4%, SM=19.9%) or on the risk for acquiring a new IMI between dry off and 0 to 10 DIM (DC=16.6%, SM=14.1%). Noninferiority analysis and mixed logistic regression analysis both showed no treatment difference in risk for a cure between dry off and 0 to 10 DIM (DC=84.8%, SM=85.7%). Cox proportional hazards regression showed no difference between treatments in quarter-level risk for clinical mastitis (DC=1.99%, SM=2.96%), cow-level risk for clinical mastitis (DC=17.0%, SM=15.3%), or on risk for removal from the herd (DC=10.7%, SM=10.3%) between dry off and 100 DIM. Finally, multivariable linear regression with repeated measures showed no overall no difference between treatments in DHIA test-day somatic cell count linear score (DC=2.19, SM=2.22), butterfat test (DC=3.84%, SM=3.86%), protein test (DC=3.02%, SM=3.02%), or 305-d mature-equivalent milk production (DC=11,817 kg, SM=11,932 kg) between calving and 100 DIM. In conclusion, DC was noninferior to SM in effecting a cure, and there was no difference in efficacy between these 2 DCT formulations as related to all other udder health or cow performance measures evaluated between dry off and 100 DIM. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Diagnosing intramammary infections: evaluation of definitions based on a single milk sample.

    PubMed

    Dohoo, I R; Smith, J; Andersen, S; Kelton, D F; Godden, S

    2011-01-01

    Criteria for diagnosing intramammary infections (IMI) have been debated for many years. Factors that may be considered in making a diagnosis include the organism of interest being found on culture, the number of colonies isolated, whether or not the organism was recovered in pure or mixed culture, and whether or not concurrent evidence of inflammation existed (often measured by somatic cell count). However, research using these criteria has been hampered by the lack of a "gold standard" test (i.e., a perfect test against which the criteria can be evaluated) and the need for very large data sets of culture results to have sufficient numbers of quarters with infections with a variety of organisms. This manuscript used 2 large data sets of culture results to evaluate several definitions (sets of criteria) for classifying a quarter as having, or not having an IMI by comparing the results from a single culture to a gold standard diagnosis based on a set of 3 milk samples. The first consisted of 38,376 milk samples from which 25,886 triplicate sets of milk samples taken 1 wk apart were extracted. The second consisted of 784 quarters that were classified as infected or not based on a set of 3 milk samples collected at 2-d intervals. From these quarters, a total of 3,136 additional samples were evaluated. A total of 12 definitions (named A to L) based on combinations of the number of colonies isolated, whether or not the organism was recovered in pure or mixed culture, and the somatic cell count were evaluated for each organism (or group of organisms) with sufficient data. The sensitivity (ability of a definition to detect IMI) and the specificity (Sp; ability of a definition to correctly classify noninfected quarters) were both computed. For all species, except Staphylococcus aureus, the sensitivity of all definitions was <90% (and in many cases<50%). Consequently, if identifying as many existing infections as possible is important, then the criteria for considering a quarter positive should be a single colony (from a 0.01-mL milk sample) isolated (definition A). With the exception of "any organism" and coagulase-negative staphylococci, all Sp estimates were over 94% in the daily data and over 97% in the weekly data, suggesting that for most species, definition A may be acceptable. For coagulase-negative staphylococci, definitions B (2 colonies from a 0.01-mL milk sample) raised the Sp to 92 and 95% in the daily and weekly data, respectively. For "any organism," using definition B raised the Sp to 88 and 93% in the 2 data sets, respectively. The final choice of definition will depend on the objectives of study or control program for which the sample was collected. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Optimization of EGFR high positive cell isolation procedure by design of experiments methodology.

    PubMed

    Levi, Ofer; Tal, Baruch; Hileli, Sagi; Shapira, Assaf; Benhar, Itai; Grabov, Pavel; Eliaz, Noam

    2015-01-01

    Circulating tumor cells (CTCs) in blood circulation may play a role in monitoring and even in early detection of metastasis patients. Due to the limited presence of CTCs in blood circulation, viable CTCs isolation technology must supply a very high recovery rate. Here, we implement design of experiments (DOE) methodology in order to optimize the Bio-Ferrography (BF) immunomagnetic isolation (IMI) procedure for the EGFR high positive CTCs application. All consequent DOE phases such as screening design, optimization experiments and validation experiments were used. A significant recovery rate of more than 95% was achieved while isolating 100 EGFR high positive CTCs from 1 mL human whole blood. The recovery achievement in this research positions BF technology as one of the most efficient IMI technologies, which is ready to be challenged with patients' blood samples. © 2015 International Clinical Cytometry Society.

  3. on-course(®) portal: a tool for in-service training and career development for biomedical scientists.

    PubMed

    Payton, Antony; Janko, Christa; Renn, Oliver; Hardman, Michael

    2013-09-01

    Successfully navigating through the jungle of biomedical postgraduate courses in Europe has recently been made possible by the release of an Innovative Medicines Initiative (IMI) funded project called on-course(®) (http://www.on-course.eu). on-course(®) lists all master, continued professional development (CPD) and PhD courses in Europe and hosts advanced search options designed by the pharmaceutical industry, academia and regulatory bodies allowing the course seeker to find courses that are most relevant for them. In addition, an IMI cross education and training topic task force has developed a set of quality standards that have been applied to CPD courses. The comprehensive nature of on-course(®) offers a new level of transparency to biomedical course provision in Europe that will help steer future education and training. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Space station microscopy: Beyond the box

    NASA Technical Reports Server (NTRS)

    Hunter, N. R.; Pierson, Duane L.; Mishra, S. K.

    1993-01-01

    Microscopy aboard Space Station Freedom poses many unique challenges for in-flight investigations. Disciplines such as material processing, plant and animal research, human reseach, enviromental monitoring, health care, and biological processing have diverse microscope requirements. The typical microscope not only does not meet the comprehensive needs of these varied users, but also tends to require excessive crew time. To assess user requirements, a comprehensive survey was conducted among investigators with experiments requiring microscopy. The survey examined requirements such as light sources, objectives, stages, focusing systems, eye pieces, video accessories, etc. The results of this survey and the application of an Intelligent Microscope Imaging System (IMIS) may address these demands for efficient microscopy service in space. The proposed IMIS can accommodate multiple users with varied requirements, operate in several modes, reduce crew time needed for experiments, and take maximum advantage of the restrictive data/ instruction transmission environment on Freedom.

  5. Course fees and academic ranking: insights from the IMI EMTRAIN on-course® database.

    PubMed

    Payton, Antony; Dallakian, Pavel; Fitton, Alexander; Payton, Anna; Hardman, Mike; Yuille, Martin

    2014-07-01

    The Innovative Medicines Initiative (IMI) funded project on-course® (http://www.on-course.eu/) lists postgraduate biomedical courses in Europe and is comprehensive for all taught and research master's courses. Using on-course®, new insights into education and training in Europe can be delivered; and here we investigate the relationship between master's course fees and university ranking. We hypothesise that higher master's course fees would be associated with higher university ranking. This was indeed the case for research master's courses and for taught master's courses for non-EU students. However, we observed no correlation between taught master's course fees for EU students and university ranking, meaning EU students are paying on average as much for courses at lower ranked universities as they are for courses at higher ranked universities. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  6. Neutral tumor evolution in myeloma is associated with poor prognosis.

    PubMed

    Johnson, David C; Lenive, Oleg; Mitchell, Jonathan; Jackson, Graham; Owen, Roger; Drayson, Mark; Cook, Gordon; Jones, John R; Pawlyn, Charlotte; Davies, Faith E; Walker, Brian A; Wardell, Christopher; Gregory, Walter M; Cairns, David; Morgan, Gareth J; Houlston, Richard S; Kaiser, Martin F

    2017-10-05

    Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory drug (IMiD) therapy. By analyzing mutant allele frequency distributions in tumors, we found that 17% to 20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in nonintensively treated patients, which is consistent with the reduced therapeutic efficacy of microenvironment-modulating IMiDs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcomes and personalizing therapy. © 2017 by The American Society of Hematology.

  7. Brain delivery research in public-private partnerships: The IMI-JU COMPACT consortium as an example.

    PubMed

    Meyer, Axel H; Untucht, Christopher; Terstappen, Georg C

    2017-07-01

    The Blood-Brain Barrier (BBB) represents a major hurdle in the development of treatments for CNS disorders due to the fact that it very effectively keeps drugs, especially biological macromolecules, out of the brain. Concomitantly with the increasing importance of biologics research on the BBB and, more specifically, on brain delivery technologies has intensified in recent years. Public-Private Partnerships (PPPs) represent an innovative opportunity to address such complex challenges as they bring together the best expertise from both industry and academia. Here we present the IMI-JU COMPACT (Collaboration on the Optimisation of Macromolecular Pharmaceutical Access to Cellular Targets) consortium working on nanocarriers for targeted delivery of macromolecules as an example. The scope of the consortium, its goals and the expertise within the consortium are outlined. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders". Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Are 6-8 year old Italian children moving away from the Mediterranean diet?

    PubMed

    Zani, C; Ceretti, E; Grioni, S; Viola, G C V; Donato, F; Feretti, D; Festa, A; Bonizzoni, S; Bonetti, A; Monarca, S; Villarini, M; Levorato, S; Carducci, A; Verani, M; Casini, B; De Donno, A; Grassi, T; Bagordo, F; Carraro, E; Bonetta, Si; Bonetta, Sa; Gelatti, U

    2016-01-01

    The Mediterranean diet (MD) is considered one of the healthiest dietary models, as it decreases the risk of chronic diseases and may modulate the organism's early response to environmental pollution. In recent decades, Mediterranean countries have been replacing their traditional diet with other less healthy eating habits, especially among children and teenagers. The aim of this study was to evaluate the MD and the level of adherence to it in 6-8 year old Italian children, in relation to residence, lifestyle, and social and family contexts. A questionnaire was administered to the children's parents in two seasons in 5 Italian towns. The diet section contained 116 questions investigating the frequency of consumption of different types of food. The Italian Mediterranean Index (IMI) was calculated according to the intake of 6 typical Mediterranean and 4 non-Mediterranean foods. On the basis of IMI score, MD adherence was classified as low (≤ 3 IMI score), medium (4-5) and high (≥ 6). Total energy load and diet composition in micro- and macronutrients were calculated from consumption frequency. Diet analysis was computed on 1164 subjects with two complete questionnaires. Body mass index, calculated for each subject, showed that 28.9% of the children were overweight, the figure varying slightly with area of residence. Our findings showed that 59.0% of the children had a low score for MD adherence. The results of this study showed that most Italian children did not follow the MD and socio-economic characteristics appeared not to be associated with type of diet.

  9. The effect of subclinical mastitis on milk yield in dairy goats.

    PubMed

    Koop, G; van Werven, T; Schuiling, H J; Nielen, M

    2010-12-01

    The aims of this study were to estimate milk yield (MY) losses associated with subclinical intramammary infection (IMI) in dairy goats and to assess if somatic cell count (SCC) can be used to estimate such MY losses. We used 2 data sets to study these questions. The first data set consisted of 5 herds. Milk production and SCC were recorded during 1 lactation. From approximately 100 does in each herd, milk samples were collected on 3 occasions during lactation for bacteriological culture. Linear mixed regression was used to estimate the effect of IMI on MY. The second data set consisted of 6 large herds, in which some of the goats had an extended lactation (≥2 yr). Milk yield and SCC data were recorded without bacteriological culture. The data showed that bacterial infection was related to an increase in SCC. Infections with major pathogens were rare and associated with a decreased MY; infection with coagulase-negative staphylococci did not affect MY, whereas infection with Corynebacterium bovis was associated with increased MY. A negative correlation was observed between SCC and MY, but the data suggested that this negative correlation was attenuated rather than caused by IMI. Furthermore, SCC seemed to be affected by MY via a dilution effect. Hypotheses about biological mechanisms behind these observations are discussed. This paper shows that MY losses caused by subclinical udder infections are limited in goats, and that SCC cannot be used to estimate the magnitude of these losses. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

    PubMed

    Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

    2012-08-01

    The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

  11. Youth fitness testing: the effect of percentile-based evaluative feedback on intrinsic motivation.

    PubMed

    Whitehead, J R; Corbin, C B

    1991-06-01

    This study was a test of Deci and Ryan's (1985) cognitive evaluation theory in a fitness testing situation. More specifically, it was a test of Proposition 2 of that theory, which posits that external events that increase or decrease perceived competence will increase or decrease intrinsic motivation. Seventh and eighth grade schoolchildren (N = 105) volunteered for an experiment that was ostensibly to collect data on a new youth fitness test (the Illinois Agility Run). After two untimed practice runs, a specially adapted version of the Intrinsic Motivation Inventory (IMI) was administered as a pretest of intrinsic motivation. Two weeks later when subjects ran again, they were apparently electronically timed. In reality, the subjects were given bogus feedback. Subjects in a positive feedback condition were told their scores were above the 80th percentile, while those in a negative feedback condition were told their scores were below the 20th percentile. Those in a control condition received no feedback. The IMI was again administered to the subjects after their runs. Multivariate and subsequent univariate tests were significant for all four subscale dependent variables (perceived interest-enjoyment, competence, effort, and pressure-tension). Positive feedback enhanced all aspects of intrinsic motivation, whereas negative feedback decreased them. In a further test of cognitive evaluation theory, path analysis results supported the prediction that perceived competence would mediate changes in the other IMI subscales. Taken together, these results clearly support cognitive evaluation theory and also may have important implications regarding motivation for those who administer youth fitness tests.

  12. Evaluation of selective dry cow treatment following on-farm culture: risk of postcalving intramammary infection and clinical mastitis in the subsequent lactation.

    PubMed

    Cameron, M; McKenna, S L; MacDonald, K A; Dohoo, I R; Roy, J P; Keefe, G P

    2014-01-01

    The objective of the study was to evaluate the utility of a Petrifilm-based on-farm culture system when used to make selective antimicrobial treatment decisions on low somatic cell count cows (<200,000 cells/mL) at drying off. A total of 729 cows from 16 commercial dairy herds with a low bulk tank somatic cell count (<250,000 cells/mL) were randomly assigned to receive either blanket dry cow therapy (DCT) or Petrifilm-based selective DCT. Cows belonging to the blanket DCT group were infused with a commercial dry cow antimicrobial product and an internal teat sealant (ITS) at drying off. Using composite milk samples collected on the day before drying off, cows in the selective DCT group were treated at drying off based on the results obtained by the Petrifilm on-farm culture system with DCT + ITS (Petrifilm culture positive), or ITS alone (Petrifilm culture negative). Quarters of all cows were sampled for standard laboratory bacteriology on the day before drying off, at 3 to 4d in milk (DIM), at 5 to 18 DIM, and from the first case of clinical mastitis occurring within 120 DIM. Multilevel logistic regression was used to assess the effect of study group (blanket or selective DCT) and resulting dry cow treatment (DCT + ITS, or ITS alone) on the risk of intramammary infection (IMI) at calving and the risk of a first case of clinical mastitis between calving and 120 DIM. According to univariable analysis, no difference was observed between study groups with respect to quarter-level cure risk and new IMI risk over the dry period. Likewise, the risk of IMI at calving and the risk of clinical mastitis in the first 120 DIM was not different between quarters belonging to cows in the blanket DCT group and quarters belonging to cows in the selective DCT group. The results of this study indicate that selective DCT based on results obtained by the Petrifilm on-farm culture system achieved the same level of success with respect to treatment and prevention of IMI over the dry period as blanket DCT and did not affect the risk of clinical mastitis in the first 120 d of the subsequent lactation. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research

    PubMed Central

    Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F.; Baumeister, Harald

    2017-01-01

    Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive–compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD. PMID:28848454

  14. Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research.

    PubMed

    Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F; Baumeister, Harald

    2017-01-01

    Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive-compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD.

  15. Energy and macronutrient content of familiar beverages interact with pre-meal intervals to determine later food intake, appetite and glycemic response in young adults.

    PubMed

    Panahi, Shirin; Luhovyy, Bohdan L; Liu, Ting Ting; Akhavan, Tina; El Khoury, Dalia; Goff, H Douglas; Harvey Anderson, G

    2013-01-01

    The objective was to compare the effects of pre-meal consumption of familiar beverages on appetite, food intake, and glycemic response in healthy young adults. Two short-term experiments compared the effect of consumption at 30 (experiment 1) or 120 min (experiment 2) before a pizza meal of isovolumetric amounts (500 mL) of water (0 kcal), soy beverage (200 kcal), 2% milk (260 kcal), 1% chocolate milk (340 kcal), orange juice (229 kcal) and cow's milk-based infant formula (368 kcal) on food intake and subjective appetite and blood glucose before and after a meal. Pre-meal ingestion of chocolate milk and infant formula reduced food intake compared to water at 30 min, however, beverage type did not affect food intake at 2h. Pre-meal blood glucose was higher after chocolate milk than other caloric beverages from 0 to 30 min (experiment 1), and after chocolate milk and orange juice from 0 to 120 min (experiment 2). Only milk reduced post-meal blood glucose in both experiments, suggesting that its effects were independent of meal-time energy intake. Combined pre- and post-meal blood glucose was lower after milk compared to chocolate milk and orange juice, but did not differ from other beverages. Thus, beverage calorie content and inter-meal intervals are primary determinants of food intake in the short-term, but macronutrient composition, especially protein content and composition, may play the greater role in glycemic control. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Teaching Health Sciences Students about Culturally Sensitive Communication between Health Professionals and Patients from Diverse Cultures

    ERIC Educational Resources Information Center

    Olivares, Mónica; Pena, Carmen

    2015-01-01

    As members of a nationally accredited research project (I?+?D+i) InterMED (ref.: FF2011-25500) being carried out in the field of Intercultural Mediation, we are aware of the mediator's delicate role in communicative interactions between health professionals and foreign population. Sales has pointed out the dangers of stereotyping minorities and…

  17. Occurrence of imidacloprid, carbendazim, and other biocides in Italian house dust: Potential relevance for intakes in children and pets.

    PubMed

    Salis, Severyn; Testa, Cecilia; Roncada, Paola; Armorini, Sara; Rubattu, Nicola; Ferrari, Angelo; Miniero, Roberto; Brambilla, Gianfranco

    2017-09-02

    The occurrence of pesticides intended for non-agricultural use was investigated in 206 dust samples drawn from vacuum-cleaner bags from residential flats in Italy. The multi-residue analysis targeted on 95 different active principles was performed with UPLC-MS/MS, with a Limit of Quantification (LOQ) of 0.008 μg/g dry weight. The results indicated the presence of imidacloprid (IMI) and carbendazim (CARB) in 30% and 26% of the samples, with a mean and P95 concentration between 1.6 and 39 and between 0.08 and 4.9 μg/g, respectively. Combined presence of two biocides was noted in 19.4% samples, of three biocides in 9.2% samples, of four biocides in 3.4% samples, and of five and six biocides in 0.5% and 1% samples, respectively. According to the estimated dust intake in infants/toddlers aged 6-24 months (16-100 mg d -1 ) and cats (200 mg d -1 ), it was possible to obtain risk characterization with respect to the Acceptable Daily Intake (ADI) for IMI of 0.060 mg/kg body weight (bw) proposed by the European Food Safety Authority (EFSA) and the chronic Population Adjusted Dose (cPAD) of 0.019 mg/kg bw d -1 by US-EPA. Under the worst-case scenario, the presence of IMI in dust indicates potential exceedance of the cPAD in kittens, to be considered as sentinel also accounting for combined exposure. This study highlights the relevance of consumer empowerment about the responsible use of pesticides as biocidal products in indoor environment.

  18. Analytical specificity and sensitivity of a real-time polymerase chain reaction assay for identification of bovine mastitis pathogens.

    PubMed

    Koskinen, M T; Holopainen, J; Pyörälä, S; Bredbacka, P; Pitkälä, A; Barkema, H W; Bexiga, R; Roberson, J; Sølverød, L; Piccinini, R; Kelton, D; Lehmusto, H; Niskala, S; Salmikivi, L

    2009-03-01

    Intramammary infection (IMI), also known as mastitis, is the most frequently occurring and economically the most important infectious disease in dairy cattle. This study provides a validation of the analytical specificity and sensitivity of a real-time PCR-based assay that identifies 11 major pathogen species or species groups responsible for IMI, and a gene coding for staphylococcal beta-lactamase production (penicillin resistance). Altogether, 643 culture isolates originating from clinical bovine mastitis, human, and companion animal samples were analyzed using the assay. The isolates represented 83 different species, groups, or families, and originated from 6 countries in Europe and North America. The analytical specificity and sensitivity of the assay was 100% in bacterial and beta-lactamase identification across all isolates originating from bovine mastitis (n = 454). When considering the entire culture collection (including also the isolates originating from human and companion animal samples), 4 Streptococcus pyogenes, 1 Streptococcus salivarius, and 1 Streptococcus sanguis strain of human origin were identified as Streptococcus uberis, and 3 Shigella spp. strains were identified as Escherichia coli, decreasing specificity to 99% in Strep. uberis and to 99.5% in E. coli. These false-positive results were confirmed by sequencing of the 16S rRNA gene. Specificity and sensitivity remained at 100% for all other bacterial targets across the entire culture collection. In conclusion, the real-time PCR assay shows excellent analytical accuracy and holds much promise for use in routine bovine IMI testing programs. This study provides the basis for evaluating the assay's diagnostic performance against the conventional bacterial culture method in clinical field trials using mastitis milk samples.

  19. Joint toxic effects of triazophos and imidacloprid on zebrafish (Danio rerio).

    PubMed

    Wu, Shenggan; Li, Xinfang; Liu, Xinju; Yang, Guiling; An, Xuehua; Wang, Qiang; Wang, Yanhua

    2018-04-01

    Pesticide contamination is more often found as a mixture of different pesticides in water bodies rather than individual compounds. However, regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and joint toxicities of triazophos (TRI) and imidacloprid (IMI) to the zebrafish (Danio rerio) using acute indices and various sublethal endpoints. Results from 96-h semi-static test indicated that the LC 50 values of TRI to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.49 (0.36-0.71) to 4.99 (2.06-6.81) mg a.i. L -1 , which were higher than those of IMI ranging from 26.39 (19.04-38.01) to 128.9 (68.47-173.6) mg a.i. L -1 . Pesticide mixtures of TRI and IMI displayed synergistic response to zebrafish embryos. Activities of carboxylesterase (CarE) and catalase (CAT) were significantly changed in most of the individual and joint exposures of pesticides compared with the control group. The expressions of 26 genes related to oxidative stress, cellular apoptosis, immune system, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis at the mRNA level revealed that zebrafish embryos were affected by the individual or joint pesticides, and greater changes in the expressions of six genes (Mn-sod, CXCL-CIC, Dio1, Dio2, tsh and vtg1) were observed when exposed to joint pesticides compared with their individual pesticides. Taken together, the synergistic effects indicated that it was highly important to incorporate joint toxicity studies, especially at low concentrations, when assessing the risk of pesticides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Introgression of an imidazolinone-resistance gene from winter wheat (Triticum aestivum L.) into jointed goatgrass (Aegilops cylindrica Host).

    PubMed

    Perez-Jones, Alejandro; Mallory-Smith, Carol A; Hansen, Jennifer L; Zemetra, Robert S

    2006-12-01

    Imidazolinone-resistant winter wheat (Triticum aestivum L.) is being commercialized in the USA. This technology allows wheat growers to selectively control jointed goatgrass (Aegilops cylindrica Host), a weed that is especially problematic because of its close genetic relationship with wheat. However, the potential movement of the imidazolinone-resistance gene from winter wheat to jointed goatgrass is a concern. Winter wheat and jointed goatgrass have the D genome in common and can hybridize and backcross under natural field conditions. Since the imidazolinone-resistance gene (Imi1) is located on the D genome, it is possible for resistance to be transferred to jointed goatgrass via hybridization and backcrossing. To study the potential for gene movement, BC(2)S(2) plants were produced artificially using imidazolinone-resistant winter wheat (cv. FS-4) as the female parent and a native jointed goatgrass collection as the male recurrent parent. FS-4, the jointed goatgrass collection, and 18 randomly selected BC(2)S(2) populations were treated with imazamox. The percentage of survival was 100% for the FS-4, 0% for the jointed goatgrass collection and 6 BC(2)S(2) populations, 40% or less for 2 BC(2)S(2) populations, and 50% or greater for the remaining 10 BC(2)S(2) populations. Chromosome counts in BC(2)S(3) plants showed a restoration of the chromosome number of jointed goatgrass, with four out of four plants examined having 28 chromosomes. Sequencing of AHASL1D in BC(2)S(3) plants derived from BC(2)S(2)-6 revealed the sexual transmission of Imi1 from FS-4 to jointed goatgrass. Imi1 conferred resistance to the imidazolinone herbicide imazamox, as shown by the in vitro assay for acetohydroxyacid synthase (AHAS) activity.

  1. Self-reported interpersonal problems and impact messages as perceived by significant others are differentially associated with the process and outcome of depression therapy.

    PubMed

    Altenstein-Yamanaka, David; Zimmermann, Johannes; Krieger, Tobias; Dörig, Nadja; Grosse Holtforth, Martin

    2017-07-01

    Interpersonal factors play a major role in causing and maintaining depression. This study sought to investigate how patients' self-perceived interpersonal problems and impact messages as perceived by significant others are interrelated, change over therapy, and differentially predict process and outcome in psychotherapy of depression. For the present study, we used data from 144 outpatients suffering from major depression that were treated within a psychotherapy study. Interpersonal variables were assessed pre- and posttherapy with the self-report Inventory of Interpersonal Problems-Circumplex Scale (IIP-32; Thomas, Brähler, & Strauss, 2011) and with the informant-based Impact Message Inventory (Caspar, Berger, Fingerle, & Werner, 2016). Patients' levels on the dimensions of Agency and Communion were calculated from both measures; their levels on Interpersonal Distress were measured with the IIP. Depressive and general symptomatology was assessed at pre-, post-, and at 3-month follow-up; patient-reported process measures were assessed during therapy. The Agency scores of IIP and IMI correlated moderately, but the Communion scores did not. IIP Communion was positively associated with the quality of the early therapeutic alliance and with the average level of cognitive-emotional processing during therapy. Whereas IIP Communion and IMI Agency increased over therapy, IIP Distress decreased. A pre-post-decrease in IIP Distress was positively associated with pre-postsymptomatic change over and above the other interpersonal variables, but pre-post-increase in IMI Agency was positively associated with symptomatic improvement from post- to 3-month follow-up. These findings suggest that significant others seem to provide important additional information about the patients' interpersonal style. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis

    PubMed Central

    Saito, Kosuke; Maekawa, Keiko; Ishikawa, Masaki; Senoo, Yuya; Urata, Masayo; Murayama, Mayumi; Nakatsu, Noriyuki; Yamada, Hiroshi; Saito, Yoshiro

    2014-01-01

    Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis. PMID:24980264

  3. 78 FR 8407 - Authorization To Manufacture and Distribute Postage Evidencing Systems; Discontinued Indicia

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... discontinuing the non-IBI or non-IMI indicia over such a short period of time it would put them at risk in the... has discussed with the industry the need to discontinue these indicia. Since the introduction of the...

  4. 'Conversion course' to allow holders of the IMI Diploma in Medical Illustration to gain a BSc in Medical Illustration from Glasgow Caledonian University.

    PubMed

    Herd, A Y; Milligan, R G

    1997-09-01

    The 'conversion course' described in this paper has been set up following discussions between the Institute of Medical Illustrators (IMI) and Glasgow Caledonian University (GCU). The 'conversion course' will take the form of a degree triple module with a credit rating of 60 Scottish Credit and Accumulation Transfer (SCOTCAT) credits at Scottish Degree (SD) level 3. This module will require the student to undertake an extended theoretical based investigative project. The project will permit the student to study in-depth an aspect of his/her specialist interest that has a particular professional relevance. The topic of the project will be negotiated between the student and a scrutiny panel under the aegis of the department of Biological Sciences at Glasgow Caledonian University. The project will be written up in the style of an academic paper for the Institute's journal. Successful students will be awarded the BSc in Medical Illustration.

  5. Identification of differentially expressed genes in response to mercury I and II stress in Trichoderma harzianum.

    PubMed

    Puglisi, Ivana; Faedda, Roberto; Sanzaro, Vincenzo; Lo Piero, Angela R; Petrone, Goffredo; Cacciola, Santa O

    2012-09-15

    Filamentous fungi are very promising organisms in both the control and the reduction of the amount of heavy metal released by human and industrial activities. In particular, Trichoderma harzianum demonstrated to be tolerant towards different heavy metals, such as mercury and cadmium, even though the mechanism underlying this tolerance is not fully understood. By using a particular strategy of the suppression subtractive hybridization technique, we were able to identify in the strain IMI 393899 of T. harzianum eight different genes up-regulated in the presence of mercury II with respect to cadmium. Among the genes identified, a possible role in the tolerance mechanism could be envisaged for hydrophobin, due to its ability to dissolve hydrophobic molecules into aqueous media. We also show that IMI 393899 grows at the same rate of control culture in the presence of mercury I and that all eight genes isolated were also up-regulated in this condition. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. An ultra-high-density map as a community resource for discerning the genetic basis of quantitative traits in maize

    USDA-ARS?s Scientific Manuscript database

    In this study, we generated a linkage map containing 1,151,856 high quality SNPs between Mo17 and B73, which were verified in the maize intermated B73'×'Mo17 (IBM) Syn10 population. This resource is an excellent complement to existing maize genetic maps available in an online database (iPlant, http:...

  7. Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy.

    PubMed

    Kini Bailur, Jithendra; Mehta, Sameet; Zhang, Lin; Neparidze, Natalia; Parker, Terri; Bar, Noffar; Anderson, Tara; Xu, Mina L; Dhodapkar, Kavita M; Dhodapkar, Madhav V

    2017-11-28

    Altered number, subset composition, and function of bone marrow innate lymphoid cells are early events in monoclonal gammopathies.Pomalidomide therapy leads to reduction in Ikzf1 and Ikzf3 and enhanced human innate lymphoid cell function in vivo.

  8. Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight.

    PubMed

    Labouré, H; Saux, S; Nicolaidis, S

    2001-03-01

    A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.

  9. Soluble Fiber with High Water-Binding Capacity, Swelling Capacity, and Fermentability Reduces Food Intake by Promoting Satiety Rather Than Satiation in Rats.

    PubMed

    Tan, Chengquan; Wei, Hongkui; Zhao, Xichen; Xu, Chuanhui; Zhou, Yuanfei; Peng, Jian

    2016-10-02

    To understand whether soluble fiber (SF) with high water-binding capacity (WBC), swelling capacity (SC) and fermentability reduces food intake and whether it does so by promoting satiety or satiation or both, we investigated the effects of different SFs with these properties on the food intake in rats. Thirty-two male Sprague-Dawley rats were randomized to four equal groups and fed the control diet or diet containing 2% konjac flour (KF), pregelatinized waxy maize starch (PWMS) plus guar gum (PG), and PWMS starch plus xanthan gum (PX) for three weeks, with the measured values of SF, WBC, and SC in the four diets following the order of PG > KF > PX > control. Food intake, body weight, meal pattern, behavioral satiety sequence, and short-chain fatty acids (SCFAs) in cecal content were evaluated. KF and PG groups reduced the food intake, mainly due to the decreased feeding behavior and increased satiety, as indicated by decreased meal numbers and increased inter-meal intervals. Additionally, KF and PG groups increased concentrations of acetate acid, propionate acid, and SCFAs in the cecal contents. Our results indicate that SF with high WBC, SC, and fermentability reduces food intake-probably by promoting a feeling of satiety in rats to decrease their feeding behavior.

  10. Soluble Fiber with High Water-Binding Capacity, Swelling Capacity, and Fermentability Reduces Food Intake by Promoting Satiety Rather Than Satiation in Rats

    PubMed Central

    Tan, Chengquan; Wei, Hongkui; Zhao, Xichen; Xu, Chuanhui; Zhou, Yuanfei; Peng, Jian

    2016-01-01

    To understand whether soluble fiber (SF) with high water-binding capacity (WBC), swelling capacity (SC) and fermentability reduces food intake and whether it does so by promoting satiety or satiation or both, we investigated the effects of different SFs with these properties on the food intake in rats. Thirty-two male Sprague-Dawley rats were randomized to four equal groups and fed the control diet or diet containing 2% konjac flour (KF), pregelatinized waxy maize starch (PWMS) plus guar gum (PG), and PWMS starch plus xanthan gum (PX) for three weeks, with the measured values of SF, WBC, and SC in the four diets following the order of PG > KF > PX > control. Food intake, body weight, meal pattern, behavioral satiety sequence, and short-chain fatty acids (SCFAs) in cecal content were evaluated. KF and PG groups reduced the food intake, mainly due to the decreased feeding behavior and increased satiety, as indicated by decreased meal numbers and increased inter-meal intervals. Additionally, KF and PG groups increased concentrations of acetate acid, propionate acid, and SCFAs in the cecal contents. Our results indicate that SF with high WBC, SC, and fermentability reduces food intake—probably by promoting a feeling of satiety in rats to decrease their feeding behavior. PMID:27706095

  11. A User’s Guide to CERC’s Field Research Facility.

    DTIC Science & Technology

    1981-10-01

    Fam,~ ~~~ 11 sIqldca Walter Mtlae iMi r,t Torrey Paintl le aceaec it Mattfmld and [att iv 1tera , Pi ,ot tloellI A’S’~ ~~ ~~ . n2K’t’ L trw: a ( Macha

  12. Extending the shelf-life of Myrothecium verrucaria, a bioherbicide

    USDA-ARS?s Scientific Manuscript database

    The bioherbicidal efficacy of freshly fermented Myrothecium verrucaria IMI 368023 (MV) mycelia formulations and MV mycelia preparations that had been freeze-dried and then stored at -20 °C for 8 years were compared. Two concentrations of each formulation (1x and 0.5x) were tested, utilizing bioassa...

  13. Evaluation of an automated milk leukocyte differential test and the California Mastitis Test for detecting intramammary infection in early- and late-lactation quarters and cows.

    PubMed

    Godden, S M; Royster, E; Timmerman, J; Rapnicki, P; Green, H

    2017-08-01

    Study objectives were to (1) describe the diagnostic test characteristics of an automated milk leukocyte differential (MLD) test and the California Mastitis Test (CMT) to identify intramammary infection (IMI) in early- (EL) and late-lactation (LL) quarters and cows when using 3 different approaches to define IMI from milk culture, and (2) describe the repeatability of MLD test results at both the quarter and cow level. Eighty-six EL and 90 LL Holstein cows were sampled from 3 Midwest herds. Quarter milk samples were collected for a cow-side CMT test, milk culture, and MLD testing. Quarter IMI status was defined by 3 methods: culture of a single milk sample, culture of duplicate samples with parallel interpretation, and culture of duplicate samples with serial interpretation. The MLD testing was completed in duplicate within 8 h of sample collection; MLD results (positive/negative) were reported at each possible threshold setting (1-18 for EL; 1-12 for LL) and CMT results (positive/negative) were reported at each possible cut-points (trace, ≥1, ≥2, or 3). We created 2 × 2 tables to compare MLD and CMT results to milk culture, at both the quarter and cow level, when using each of 3 different definitions of IMI as the referent test. Paired MLD test results were compared with evaluate repeatability. The MLD test showed excellent repeatability. The choice of definition of IMI from milk culture had minor effects on estimates of MLD and CMT test characteristics. For EL samples, when interpreting MLD and CMT results at the quarter level, and regardless of the referent test used, both tests had low sensitivity (MLD = 11.7-39.1%; CMT = 0-52.2%) but good to very good specificity (MLD = 82.1-95.2%; CMT = 68.1-100%), depending on the cut-point used. Sensitivity improved slightly if diagnosis was interpreted at the cow level (MLD = 25.6-56.4%; CMT = 0-72.2%), though specificity generally declined (MLD = 61.8-100%; CMT = 25.0-100%) depending on the cut-point used. For LL samples, when interpreted at the quarter level, both tests had variable sensitivity (MLD = 46.6-84.8%; CMT = 9.6-72.7%) and variable specificity (MLD = 59.2-79.8%; CMT = 52.5-97.3%), depending on the cut-point used. Test sensitivity improved if interpreted at the cow level (MLD = 59.6-86.4%; CMT = 19.1-86.4%), though specificity declined (MLD = 32.4-56.8%; CMT = 14.3-92.3%). Producers considering adopting either test for LL or EL screening programs will need to carefully consider the goals and priorities of the program (e.g., whether to prioritize test sensitivity or specificity) when deciding on the level of interpretation (quarter or cow) and when selecting the optimal cut-point for interpreting test results. Additional validation studies and large randomized field studies will be needed to evaluate the effect of adopting either test in selective dry cow therapy or fresh cow screening programs on udder health, antibiotic use, and economics. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  14. A Comparative Evaluation of Computer-Managed and Instructor-Managed Instruction.

    ERIC Educational Resources Information Center

    Ellis, John A.

    This study compares an instructor-managed (IMI) and a computer-managed (CMI) version of a modularized, individualized Navy Training course; the main difference between groups was in testing and remediation. Subjects were 240 students enrolled in the Propulsion Engineering School at Great Lakes, Illinois, who were divided into three groups: CMI…

  15. The use of automated weather stations for irrigation management in the Jordan Valley

    USDA-ARS?s Scientific Manuscript database

    We discuss an irrigation management information system approach developed by NCARE researchers with the help of USDA-ARS. The system is capable of providing farmers with online crop water requirements based on automated meteorological data published on the internet (www.ncare.gov.jo/imis, and www.m...

  16. Detection of DNA Adducts in Human Breast Tissue

    DTIC Science & Technology

    1998-07-01

    the right are from triplicate labeling and detection of egg yoke phosphatidic acid . Fig. 6 Detection of IMI2-labeled 5’-deoxynucleotides by MALDI-MS...ethanesulfonic acid (Sigma, St. Louis, MO), and adjusting the pH with 1 N sodium hydroxide. Any over-adjustment was corrected with 1 M sulfuric acid . Sucrose

  17. Canopy openness, understory light environments, and oak regeneration

    Treesearch

    Brian C. McCarthy; Scott A. Robison

    2003-01-01

    Understory light environments were evaluated in four mixed-oak forests in southern Ohio using hemispherical photography. Within each forest, plots were divided into nine treatment combinations based on three pretreatment fire categories and three Integrated Moisture Index (IMI) categories. For each of 108 photographs we determined the percentage of open sky, direct...

  18. A GIS-derived integrated moisture index

    Treesearch

    Louis R. Iverson; Anantha M. Prasad

    2003-01-01

    A geographic information system (GIS) approach was used in conjunction with forest-plot data to develop an integrated moisture index (IMI) that is being used to stratify and help explain landscape-level phenomena in the four study areas. Several landscape features (a slope-aspect shading index, cumulative flow of water downslope, curvature of the landscape, and water-...

  19. 77 FR 59599 - Notice of Public Meeting: Designing for Impact IV: Workshop on Building the National Network for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... Innovation (IMIs) and to provide an opportunity for public comment on the proposal. The discussion at the... innovation infrastructure to support regional manufacturing and ensuring that our manufacturing sector is a... DEPARTMENT OF ENERGY Office of Energy Efficiency and Renewable Energy Notice of Public Meeting...

  20. Enterobacter cloacae complex isolated from shrimps from Vietnam encoding blaIMI-1, resistant to carbapenems but not cephalosporins.

    PubMed

    Brouwer, Michael S M; Rapallini, Michel; Geurts, Yvon; Harders, Frank; Bossers, Alex; Mevius, Dik J; Wit, Ben; Veldman, Kees T

    2018-04-23

    In August of 2017, a batch of Penaeus monodon (Asian tiger shrimp) and Penaues vannamei (White leg shrimp), originating from fish farms in Vietnam, were screened for the presence of carbapenamase producing Enterobacteriaceae (CPE).…. Copyright © 2018 American Society for Microbiology.

  1. Psychometric properties of the Intrinsic Motivation Inventory in a competitive sport setting: a confirmatory factor analysis.

    PubMed

    McAuley, E; Duncan, T; Tammen, V V

    1989-03-01

    The present study was designed to assess selected psychometric properties of the Intrinsic Motivation Inventory (IMI) (Ryan, 1982), a multidimensional measure of subjects' experience with regard to experimental tasks. Subjects (N = 116) competed in a basketball free-throw shooting game, following which they completed the IMI. The LISREL VI computer program was employed to conduct a confirmatory factor analysis to assess the tenability of a five factor hierarchical model representing four first-order factors or dimensions and a second-order general factor representing intrinsic motivation. Indices of model acceptability tentatively suggest that the sport data adequately fit the hypothesized five factor hierarchical model. Alternative models were tested but did not result in significant improvements in the goodness-of-fit indices, suggesting the proposed model to be the most accurate of the models tested. Coefficient alphas for the four dimensions and the overall scale indicated adequate reliability. The results are discussed with regard to the importance of accurate assessment of psychological constructs and the use of linear structural equations in confirming the factor structures of measures.

  2. Non-Metal Doped Titania Photocatalysts for the Degradation of Neonicotinoid Insecticides Under Visible Light Irradiation.

    PubMed

    Joseph, Amala Infant Joice; Thiripuranthagan, Sivakumar

    2018-05-01

    Recombination of e-/h+ pair, the major issue of any titania based photocatalytic material, is addressed here by doping non-metals such as C, N, B, F into the lattice of nano TiO2. The as-synthesised catalysts were characterized by using various instrumental techniques such as X-ray diffraction (XRD), UV-Diffuse reflectance spectroscopy (UV-DRS), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Nanosize of titania was confirmed by both XRD and TEM studies. Visible light inactivity of TiO2 is overcome by C, N, B, F doped titania catalysts in the degradation of neonicotinoid type insecticides namely imidacloprid (IMI) and thiamethoxam (TMX). The degradation efficiencies of the catalysts under different irradiations namely UV, visible and solar were compared. Among the catalysts, CNBF/TiO2 degraded IMI completely at 150, 240 and 330 min whereas TMX has been degraded completely at 210, 270 and 420 min under UV, solar and visible irradiations respectively. The recyclability test of CNBF/TiO2 confirmed its stability towards photocatalytic reaction.

  3. Photosynthetic Performance of the Imidazolinone Resistant Sunflower Exposed to Single and Combined Treatment by the Herbicide Imazamox and an Amino Acid Extract

    PubMed Central

    Balabanova, Dobrinka A.; Paunov, Momchil; Goltsev, Vasillij; Cuypers, Ann; Vangronsveld, Jaco; Vassilev, Andon

    2016-01-01

    The herbicide imazamox may provoke temporary yellowing and growth retardation in IMI-R sunflower hybrids, more often under stressful environmental conditions. Although, photosynthetic processes are not the primary sites of imazamox action, they might be influenced; therefore, more information about the photosynthetic performance of the herbicide-treated plants could be valuable for a further improvement of the Clearfield technology. Plant biostimulants have been shown to ameliorate damages caused by different stress factors on plants, but very limited information exists about their effects on herbicide-stressed plants. In order to characterize photosynthetic performance of imazamox-treated sunflower IMI-R plants, we carried out experiments including both single and combined treatments by imazamox and a plant biostimulants containing amino acid extract. We found that imazamox application in a rate of 132 μg per plant (equivalent of 40 g active ingredient ha−1) induced negative effects on both light-light dependent photosynthetic redox reactions and leaf gas exchange processes, which was much less pronounced after the combined application of imazamox and amino acid extract. PMID:27826304

  4. Genetic relatedness and virulence factors of bovine Staphylococcus aureus isolated from teat skin and milk.

    PubMed

    da Costa, L B; Rajala-Schultz, P J; Hoet, A; Seo, K S; Fogt, K; Moon, B S

    2014-11-01

    The objective of this study was to assess the role of teat skin colonization in Staphylococcus aureus intramammary infections (IMI) by evaluating genetic relatedness of Staph. aureus isolates from milk and teat skin of dairy cows using pulsed-field gel electrophoresis and characterizing the isolates based on the carriage of virulence genes. Cows in 4 known Staph. aureus-positive herds were sampled and Staph. aureus was detected in 43 quarters of 20 cows, with 10 quarters positive in both milk and skin (20 isolates), 18 positive only in milk, and 15 only on teat skin. Quarters with teat skin colonized with Staph. aureus were 4.5 times more likely to be diagnosed with Staph. aureus IMI than quarters not colonized on teat skin. Three main clusters were identified by pulsed-field gel electrophoresis using a cutoff of 80% similarity. All 3 clusters included both milk and skin isolates. The majority of isolates (72%) belonged to one predominant cluster (B), with 60% of isolates in the cluster originating from milk and 40% from teat skin. Genotypic variability was observed within 10 pairs (formed by isolates originating from milk and teat skin of the same quarter), where isolates in 5 out of the 10 pairs belonged to the same cluster. Forty-two virulence factors were screened using PCR. Some virulence factors were carried more frequently by teat skin isolates than by milk isolates or isolates from quarters with high somatic cell counts. Isolates in the predominant cluster B carried virulence factors clfA and clfB significantly more often than isolates in the minor clusters, which may have assisted them in becoming predominant in the herds. The present findings suggest that teat skin colonization with Staph. aureus can be an important factor involved in Staph. aureus IMI. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds

    PubMed Central

    2013-01-01

    Background Treatment of subclinical mastitis during lactation can have both direct (individual animal level) and indirect (population level) effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. Results The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI) caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. Conclusion In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can have indirect effects including preventing new IMI and reducing incidence of clinical mastitis within dairy herds. Strain specific transmission parameter estimates for S. aureus MLST clonal complexes 5, 97 and 705 in 2 commercial dairy herds are also reported. PMID:23398676

  6. Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds.

    PubMed

    Barlow, John W; Zadoks, Ruth N; Schukken, Ynte H

    2013-02-11

    Treatment of subclinical mastitis during lactation can have both direct (individual animal level) and indirect (population level) effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI) caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can have indirect effects including preventing new IMI and reducing incidence of clinical mastitis within dairy herds. Strain specific transmission parameter estimates for S. aureus MLST clonal complexes 5, 97 and 705 in 2 commercial dairy herds are also reported.

  7. Identifying the major bacteria causing intramammary infections in individual milk samples of sheep and goats using traditional bacteria culturing and real-time polymerase chain reaction.

    PubMed

    Rovai, M; Caja, G; Salama, A A K; Jubert, A; Lázaro, B; Lázaro, M; Leitner, G

    2014-09-01

    Use of DNA-based methods, such as real-time PCR, has increased the sensitivity and shortened the time for bacterial identification, compared with traditional bacteriology; however, results should be interpreted carefully because a positive PCR result does not necessarily mean that an infection exists. One hundred eight lactating dairy ewes (56 Manchega and 52 Lacaune) and 24 Murciano-Granadina dairy goats were used for identifying the main bacteria causing intramammary infections (IMI) using traditional bacterial culturing and real-time PCR and their effects on milk performance. Udder-half milk samples were taken for bacterial culturing and somatic cell count (SCC) 3 times throughout lactation. Intramammary infections were assessed based on bacteria isolated in ≥2 samplings accompanied by increased SCC. Prevalence of subclinical IMI was 42.9% in Manchega and 50.0% in Lacaune ewes and 41.7% in goats, with the estimated milk yield loss being 13.1, 17.9, and 18.0%, respectively. According to bacteriology results, 87% of the identified single bacteria species (with more than 3 colonies/plate) or culture-negative growth were identical throughout samplings, which agreed 98.9% with the PCR results. Nevertheless, the study emphasized that 1 sampling may not be sufficient to determine IMI and, therefore, other inflammatory responses such as increased SCC should be monitored to identify true infections. Moreover, when PCR methodology is used, aseptic and precise milk sampling procedures are key for avoiding false-positive amplifications. In conclusion, both PCR and bacterial culture methods proved to have similar accuracy for identifying infective bacteria in sheep and goats. The final choice will depend on their response time and cost analysis, according to the requirements and farm management strategy. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Concentrations of tilmicosin in mammary gland secretions of dairy cows following subcutaneous administration of one or two doses of an experimental preparation of tilmicosin and its efficacy against intramammary infections caused by Staphylococcus aureus.

    PubMed

    Mendoza, Jesus; Martínez-Cortés, Ismael; López-Ordaz, Reyes; Gutiérrez, Lilia; Sumano, Hector

    2016-09-01

    OBJECTIVE To determine the concentration of tilmicosin in mammary gland secretions of dairy cows following administration of an experimental preparation once or twice during the dry period (45-day period immediately prior to calving during which cows are not milked) and to evaluate its efficacy for the treatment of cows with intramammary infections (IMIs) caused by Staphylococcus aureus at dry off (cessation of milking; first day of dry period), compared with that of an intramammary infusion of ceftiofur. ANIMALS 172 cows. PROCEDURES Milk samples were collected for microbiological culture 5 days before dry off and at calving and 15 and 30 days after calving. Cows with Staphylococcus IMIs were randomly assigned to receive an experimental preparation of tilmicosin (20 mg/kg, SC) once at dry off (n = 58) or at dry off and again 20 days later (56) or receive a long-acting intramammary preparation of ceftiofur (500 mg/mammary gland; 56) at dry off. Mammary gland secretions were collected from 5 cows in the tilmicosin-treated groups every 5 days after dry off until calving for determination of tilmicosin concentration. RESULTS Mean maximum concentration of tilmicosin in mammary gland secretions ranged from 14.4 to 20.9 μg/mL after the first dose and was 17.1 μg/mL after the second dose. The bacteriologic cure rate was 100% for all 3 treatments. Tilmicosin was detectable for 0 and 18 days after calving in the milk of cows treated with 1 and 2 doses of tilmicosin, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Administration of an experimental preparation of tilmicosin (20 mg/kg, SC) once to dairy cows at dry off might be useful for the treatment of S aureus IMIs.

  9. Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations

    PubMed Central

    Yu, Rilei; Craik, David J.; Kaas, Quentin

    2011-01-01

    α-Conotoxins potently inhibit isoforms of nicotinic acetylcholine receptors (nAChRs), which are essential for neuronal and neuromuscular transmission. They are also used as neurochemical tools to study nAChR physiology and are being evaluated as drug leads to treat various neuronal disorders. A number of experimental studies have been performed to investigate the structure-activity relationships of conotoxin/nAChR complexes. However, the structural determinants of their binding interactions are still ambiguous in the absence of experimental structures of conotoxin-receptor complexes. In this study, the binding modes of α-conotoxin ImI to the α7-nAChR, currently the best-studied system experimentally, were investigated using comparative modeling and molecular dynamics simulations. The structures of more than 30 single point mutants of either the conotoxin or the receptor were modeled and analyzed. The models were used to explain qualitatively the change of affinities measured experimentally, including some nAChR positions located outside the binding site. Mutational energies were calculated using different methods that combine a conformational refinement procedure (minimization with a distance dependent dielectric constant or explicit water, or molecular dynamics using five restraint strategies) and a binding energy function (MM-GB/SA or MM-PB/SA). The protocol using explicit water energy minimization and MM-GB/SA gave the best correlations with experimental binding affinities, with an R2 value of 0.74. The van der Waals and non-polar desolvation components were found to be the main driving force for binding of the conotoxin to the nAChR. The electrostatic component was responsible for the selectivity of the various ImI mutants. Overall, this study provides novel insights into the binding mechanism of α-conotoxins to nAChRs and the methodological developments reported here open avenues for computational scanning studies of a rapidly expanding range of wild-type and chemically modified α-conotoxins. PMID:21390272

  10. IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

    PubMed

    Wójtowicz, Agnieszka; Gresnigt, Mark S; Lecompte, Thanh; Bibert, Stephanie; Manuel, Oriol; Joosten, Leo A B; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans H; Weisser, Maja; Mueller, Nicolas J; Meylan, Pascal R; Steiger, Jürg; Kutalik, Zoltan; Pascual, Manuel; van Delden, Christian; van de Veerdonk, Frank L; Bochud, Pierre-Yves

    2015-05-15

    Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. [Neoliberalism in health: the torture of the health care workers of the Bogota's Instituto Materno Infantil (child and maternity hospital)].

    PubMed

    Abadía, César B; Pinilla, María Y A; Ariza, Katerine R; Ruíz, Héctor C S

    2012-06-01

    To link, from a historical point of view, the most significant transformations of the Instituto Materno Infantil (IMI) [the oldest child and maternity hospital of the country] during its process of crisis, closure and liquidation with the experiences of the hospital workers. To find experience-based and theoretical elements that can interconnect the process of health care privatization of the country with the workers' experiences of resistance and pain/suffering. Critically-oriented ethnography based on continuous collective field work, historical research (primary and secondary sources) and semi-structured interviews with 5 women who worked at the IMI for more than 15 years. A time line of 4 main periods: Los años de gloria [The golden years] (up to 1990); Llega el neoliberalismo [Neoliberalism arrives] (1990-2000); La crisis y las resistencias [Crisis and resistances] (2001-2005); and Liquidación [Liquidation (2006-20??)]. The narratives of the interviewed women unveil multiple aggressions that have intensified since 2006, have caused pain and suffering and are examples of violations of human and labour rights. We suggest to analyze the links between the different kinds of violence and pain and suffering as torture. This category is defined as the set of violent actions that cause physical and emotional pain, which are performed by actors in positions of power over other people who challenge that power and are part of modern States' ideological principles around a defined moral social order. For the IMI workers' case, the ideological principle that is being challenged is health care neoliberalism. From the analyses of bureaucracy, confinement, torturing agents, and the breaking-off of the body-mind unit we conclude that this relationship between neoliberalism and torture aims to eliminate the last health care workers of the country who had job stability and full-benefits through public labour contracts. Their elimination furthers the accumulation of capital generated by increasing over-exploitation of labour and commodification of health care.

  12. Evaluation of minor pathogen intramammary infection, susceptibility parameters, and somatic cell counts on the development of new intramammary infections with major mastitis pathogens.

    PubMed

    Reyher, K K; Dohoo, I R; Scholl, D T; Keefe, G P

    2012-07-01

    Major mastitis pathogens such as Staphylococcus aureus, Streptococcus uberis, Streptococcus dysgalactiae, and coliforms are usually considered more virulent and damaging to the udder than minor mastitis pathogens such as Corynebacterium spp. and coagulase-negative staphylococci (CNS). The current literature comprises several studies (n=38) detailing analyses with conflicting results as to whether intramammary infections (IMI) with the minor pathogens decrease, increase, or have no effect on the risk of a quarter acquiring a new IMI (NIMI) with a major pathogen. The Canadian Bovine Mastitis Research Network has a large mastitis database derived from a 2-yr data collection on a national cohort of dairy farms, and data from this initiative were used to further investigate the effect of IMI with minor pathogens on the acquisition of new major pathogen infections (defined as a culture-positive quarter sample in a quarter that had been free of that major pathogen in previous samples in the sampling period). Longitudinal milk samplings of clinically normal udders taken over several 6-wk periods as well as samples from cows pre-dry-off and postcalving were used to this end (n=80,397 quarter milk samples). The effects of CNS and Corynebacterium spp. on the major mastitis pathogens Staph. aureus, Strep. uberis, Strep. dysgalactiae, and coliform bacteria (Escherichia coli and Klebsiella spp.) were investigated using risk ratio analyses and multilevel logistic regression models. Quarter-, cow- and herd-level susceptibility parameters were also evaluated and were able to account for the increased susceptibility that exists within herds, cows and quarters, removing it from estimates for the effects of the minor pathogens. Increased quarter-level susceptibility was associated with increased risk of major pathogen NIMI for all pathogens except the coliforms. Increased somatic cell count was consistently associated with elevated risk of new major pathogen infections, but this was assumed to be a result of low sensitivity of bacteriology to diagnose major pathogen NIMI expediently and accurately. The presence of CNS in the sample 2 samplings before the occurrence of a NIMI increased the odds of experiencing a Staph. aureus NIMI 2.0 times, making the presence of CNS a risk factor for acquiring a Staph. aureus NIMI. Even with this extensive data set, power was insufficient to make a definitive statement about the effect of minor pathogen IMI on the acquisition of major pathogen NIMI. Definitively answering questions of this nature are likely to require an extremely large data set dedicated particularly to minor pathogen presence and NIMI with major pathogens. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Locating and Evaluating Sea-Disposed Munitions--Examples from the Hawaii Undersea Military Munitions Assessment (HUMMA) Project

    NASA Astrophysics Data System (ADS)

    Edwards, M.; Wilkens, R. H.; Kelley, C.; de Carlo, E. H.; MacDonald, K.; Garcia, S.; Vanwoerkom, M.; Payne, Z.; Dupra, V.; Rosete, M.; Cox, M.; Fineran, S.; King, J. C.; Carton, G.

    2009-12-01

    The Army, under its Environmental Quality Technology (EQT) Program funded the HUMMA Project to assess the location of, and potential risk to human health posed by, sea disposed munitions (discarded military munitions (DMM)) at a study site south of Pearl Harbor, Hawai‘i known as HI-05. These conventional and chemical munitions are believed to have been exposed to undersea biochemical and mechanical erosion since the late 1940’s. To locate <2-meter long DMM at depths of 300-600 meters, we used a series of nested surveys beginning with an IMI-120 sidescan sonar survey of HI-05. From backscatter data gridded into 0.5-2m cells, we identified trails of highly reflective targets as candidate study sites. We initially surveyed these sites using a towed video camera. Subsequently, during a 12-day program aboard the R/V Kaimikai-o-Kanaloa, we surveyed selected targets using PISCES submersibles and an RCV-150 remotely operated vehicle operated by the Hawaii Undersea Research Lab. Every trail of reflective targets identified in the IMI-120 data was subsequently shown to contain DMM of various types. In combination with completing optical surveys to augment the IMI-120 acoustic data, the PISCES submersibles collected 96 sediment and 24 water samples within 1 and 2 meters of high-interest DMM as well as comparative background sites. The Edgewood Chemical and Biological Center supported dive operations to ensure crew personnel were not exposed to chemical agents (CA) and processed samples on board to determine if CA was present. The processed samples were then packaged and shipped to various shore-based laboratories to determine the presence of energetics and metals. Upon completion of the diving program, various species of locally consumed snapper and shrimp were collected near several of the sediment and water sample sites for analogous laboratory analyses. Our approach proved to be highly successful, identifying in a 5-day long IMI-120 survey the location of dozens of munitions trails containing ~2,000 munitions. At the 0.5m grid cell size for the backscatter data, it is even possible to identify trails of different types of munitions. Backscatter maps were critical for directing PISCES operations during sampling, including returning to specific 1-m long munitions on separate dives. These maps now serve as the foundation of a database that will allow near-bottom instruments including submersibles to operate more safely in the 69 km2 field area. At the time of this abstract preparation, sample analysis is still underway, but it will be completed in time to present the results at the December meeting.

  14. Distribution of non-aureus staphylococci species in udder quarters with low and high somatic cell count, and clinical mastitis.

    PubMed

    Condas, Larissa A Z; De Buck, Jeroen; Nobrega, Diego B; Carson, Domonique A; Roy, Jean-Philippe; Keefe, Greg P; DeVries, Trevor J; Middleton, John R; Dufour, Simon; Barkema, Herman W

    2017-07-01

    The effect of non-aureus staphylococci (NAS) in bovine mammary health is controversial. Overall, NAS intramammary infections (IMI) increase somatic cell count (SCC), with an effect categorized as mild, mostly causing subclinical or mild to moderate clinical mastitis. However, based on recent studies, specific NAS may affect the udder more severely. Some of these apparent discrepancies could be attributed to the large number of species that compose the NAS group. The objectives of this study were to determine (1) the SCC of quarters infected by individual NAS species compared with NAS as a group, culture-negative, and major pathogen-infected quarters; (2) the distribution of NAS species isolated from quarters with low SCC (<200,000 cells/mL) and high SCC (≥200,000 cells/mL), and clinical mastitis; and (3) the prevalence of NAS species across quarters with low and high SCC. A total of 5,507 NAS isolates, 3,561 from low SCC quarters, 1,873 from high SCC quarters, and 73 from clinical mastitis cases, were obtained from the National Cohort of Dairy Farms of the Canadian Bovine Mastitis Research Network. Of quarters with low SCC, high SCC, or clinical mastitis, 7.6, 18.5, and 4.3% were NAS positive, respectively. The effect of NAS IMI on SCC was estimated using mixed-effect linear regression; prevalence of NAS IMI was estimated using Bayesian analyses. Mean SCC of NAS-positive quarters was 70,000 cells/mL, which was higher than culture-negative quarters (32,000 cells/mL) and lower than major pathogen-positive quarters (129,000 to 183,000 cells/mL). Compared with other NAS species, SCC was highest in quarters positive for Staphylococcus capitis, Staphylococcus gallinarum, Staphylococcus hyicus, Staphylococcus agnetis, or Staphylococcus simulans. In NAS-positive quarters, Staphylococcus xylosus (12.6%), Staphylococcus cohnii (3.1%), and Staphylococcus equorum (0.6%) were more frequently isolated from quarters with low SCC than other NAS species, whereas Staphylococcus sciuri (14%) was most frequently isolated from clinical mastitis cases. Finally, in NAS-positive quarters, Staphylococcus chromogenes, S. simulans, Staphylococcus epidermidis, and Staphylococcus haemolyticus were isolated with similar frequency from among low SCC and high SCC quarters and clinical mastitis cases. Staphylococcus chromogenes, S. simulans, S. xylosus, S. haemolyticus, S. epidermidis, S. agnetis, Staphylococcus arlettae, S. capitis, S. gallinarum, S. sciuri, and Staphylococcus warneri were more prevalent in high than in low SCC quarters. Because the NAS are a large, heterogeneous group, considering them as a single group rather than at the species, or even subspecies level, has undoubtedly contributed to apparent discrepancies among studies as to their distribution and importance in IMI and mastitis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. A Comparison of Aircraft Maintenance Organizational Structures

    DTIC Science & Technology

    1992-09-01

    Outputs ... ...................... 85 Appendix E : Double Cross-Validation ........... 117 Appendix F: Exchange of Independent Variables...splits into three major production branches (6). See Figure 8. 26 Aircraf t Interm ia•’ e Maintenance Off icerzI A ssistantAIKO I 1|A/ant a A Traiing...responsible for all aircraft maintenance activities, see Figure 9 (4:3). rdor ! E •; e Techn•1i Se~rvices Wff oE r I f .1 Bass Airaraf t Iaintenanoc E

  16. Microstructural Characterization of HSLA-100 GMA-Weldments

    DTIC Science & Technology

    1987-09-01

    Intermeiate Oxygen Regime ----------- 66 D.) Schematic CCT Diagram - --------------- 66 9 ACKNOWLEDGEMENTS I wish to express my appreciation to my thesis...have been observed in this research [review Figures 31 (a), (b) and 35 (a)]. Figure 38 (d) shows a schematic CCT diagram reported by Glover (Ref. 5) and...Regime B.) High Ox. gen Regime C. )Interme late Oxygen Regime D.1 Schematic CCT Diagram 66 LIST OF REFERENCES 1. Anderson, T.L., Hyatt J A West, J.C

  17. A survey of imidacloprid levels in water sources potentially frequented by honey bees (Apis mellifera) in the Eastern U.S.

    USDA-ARS?s Scientific Manuscript database

    This study was undertaken to examine contamination levels of imidacloprid (IMI), a water soluble neonicotinoid insecticide, in still or slow moving water sources of the sort often frequented by honey bees, Apis mellifera. Honey bees frequent open water to transport water into the hive for consumpti...

  18. Advance Planning Briefing for Industry. Technology Requirements Briefings

    DTIC Science & Technology

    2009-02-17

    procedure drills through complex multiplayer interactions representative of a motorcade under heavy attack. The tool shall provide a first-person...Integrated Munitions Effect Assessment IMI Interactive Multimedia Instruction IP Internet Protocol IPE Intelligence Preparation of the Environment IR...CTTSO Programs and Mission Areas/Subgroups 13 Requirement Descriptions Blast Effects and Mitigation (BX) 16 Chemical, Biological, Radiological, and

  19. Study on the Feasibility of Mass Area Ordnance Decontamination

    DTIC Science & Technology

    1974-08-15

    and Armor Plate Protection 11-50 11-20 Bucket Modifications 11-53 Appendices Figure Page III-1 The Relationship Between Rippability and Seismic...FK S. .. . ... L, i ! ,, ,,i , , W~AM0RPHIC ROK MINERALS 9 ORESm n, imI I’𔄃 1.. I 1. 1 .t’ I.* [ FIGURE III-l: The Relationship Between Rippability

  20. Development of an Integrated Moisture Index for predicting species composition

    Treesearch

    Louis R. Iverson; Charles T. Scott; Martin E. Dale; Anantha Prasad

    1996-01-01

    A geographic information system (GIS) approach was used to develop an Integrated Moisture Index (IMI), which was used to predict species composition for Ohio forests. Several landscape features (a slope-aspect shading index, cumulative flow of water downslope, curvature of the landscape, and the water-holding capacity of the soil) were derived from elevation and soils...

  1. Panama: Political and Economic Conditions and U.S. Relations

    DTIC Science & Technology

    2008-07-31

    but the September 1, 2007 election of Pedro Miguel González to head Panama’s legislature for one year delayed consideration. González is wanted in...term. Current Assembly president Pedro Miguel González, wanted in the United States for his alleged role in the murder of a U.S. serviceman in Panama in...Administration negotiated the Panama Canal Treaties. On September 1, 2007, Panama’s Legislative Assembly elected Pedro Miguel González of the ruling PRD

  2. Tailoring Multimedia Instruction to Soldier Needs

    DTIC Science & Technology

    2014-12-01

    Pretest Score (Mean % Items Correct) 39% 34% 48% 51% 51% 45% Posttest (Mean % Items Correct) 47% 44% 66% 60% 63% 56...Stepwise regression was used to examine the relationship between Soldiers’ posttest scores (criterion) and their pretest scores, training time, type of...differences among IMI types had no effect.) Pretest scores predicted posttest scores for both Adjust Indirect Fire (βstandardized = .66, t = 6.36

  3. Evaluation of Factors Contributing to the Achievement of Students Participating in a Culturally Responsive Curriculum in Hawai`i Public Schools

    ERIC Educational Resources Information Center

    Bowditch, Scott A.

    2013-01-01

    This research explored the effectiveness of "Ka Hana 'Imi Na 'auao," a culturally responsive science curriculum developed for Hawaiian and other students in Hawai'i high schools. An instrument, The Culturally Responsive Science Perception (CRSP) inventory was developed to measure students' (a) perceptions of their science self-efficacy,…

  4. 75 FR 38179 - Proposed Collection; Comment Request for Forms W-8BEN, W-8ECI, W-8EXP, and W-8IMY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... States Tax Withholding, Form W-8ECI, Certificate of Foreign Person's Claim for Exemption From Withholding on Income Effectively Connected With the Conduct of a Trade or Business in the United States, Form W-8EXP, Certificate of Foreign Government or Other Foreign Organization for United States Tax Withholding...

  5. [Prevention of intramammary infections in dairy cows by the use of a premilking teat dip method with a foaming iodophor dip agent].

    PubMed

    Falkenberg, U; Tenhagen, B A; Baumgärtner, B; Heuwieser, W

    2002-10-01

    In this study we investigated the efficacy of premilking teat dipping with a foaming iodophor teat dip in a negative controlled field study. Incidence of new intramammary infections (IMI), incidence of clinical mastitis, influence on somatic cell count (SCC) and the characteristics of udder tissue and teats were used as parameters to evaluate clinical efficacy. Predipping was compared with a negative control using a split-udder experimental design. Right teats were predipped with a foaming disinfectant containing 0.27% iodine while left teats served as controls. The latter were conventionally cleaned with damp cloth towels and dried manually with disposable paper towels ("best cleaning practice"). All teats were dipped after milking with the same dip. There were no differences between treated and control quarters with respect to incidence of new IMI during the study period (treated quarters: 6.6% vs. untreated: 6.95%), incidence of clinical mastitis (30 cases in the treatment group vs. 39 cases in the control group) and geometric mean of SCC of quarter milk samples. Spectrum of detected pathogens was also comparable. Condition of udder tissue and teat ducts did not differ between treated and control quarters.

  6. Evolutionary and social consequences of introgression of nontransgenic herbicide resistance from rice to weedy rice in Brazil.

    PubMed

    Merotto, Aldo; Goulart, Ives C G R; Nunes, Anderson L; Kalsing, Augusto; Markus, Catarine; Menezes, Valmir G; Wander, Alcido E

    2016-08-01

    Several studies have expressed concerns about the effects of gene flow from transgenic herbicide-resistant crops to their wild relatives, but no major problems have been observed. This review describes a case study in which what has been feared in transgenics regarding gene flow has actually changed biodiversity and people's lives. Nontransgenic imidazolinone-resistant rice (IMI-rice) cultivars increased the rice grain yield by 50% in southern Brazil. This increase was beneficial for life quality of the farmers and also improved the regional economy. However, weedy rice resistant to imidazolinone herbicides started to evolve three years after the first use of IMI-rice cultivars. Population genetic studies indicate that the herbicide-resistant weedy rice was mainly originated from gene flow from resistant cultivars and distributed by seed migration. The problems related with herbicide-resistant weedy rice increased the production costs of rice that forced farmers to sell or rent their land. Gene flow from cultivated rice to weedy rice has proven to be a large agricultural, economic, and social constraint in the use of herbicide-resistant technologies in rice. This problem must be taken into account for the development of new transgenic or nontransgenic rice technologies.

  7. Lessons with Living Harvest Mice: An empirical study of their effects on intrinsic motivation and knowledge acquisition

    NASA Astrophysics Data System (ADS)

    Wilde, Matthias; Hußmann, Jona Samuel; Lorenzen, Simone; Meyer, Annika; Randler, Christoph

    2012-12-01

    The aim of this study was to evaluate the effects of living animals on pupils' intrinsic motivation and knowledge. Various studies from the late 1970s and 1980s stress the high effectiveness of authentic learning experiences in pupils' knowledge acquisition. However, there are only few current empirical studies on this topic. The research question of our study is to assess whether the use of living animals in the biology classroom supports intrinsic motivation and knowledge acquisition. In a pre-/post-test design, 185 fifth graders received two different treatments: the experimental group (N = 74) was taught with living harvest mice (Micromys minutus) and the control group (N = 111) received lessons with the same content which was presented in short film clips on laptop computers. Knowledge acquisition was assessed with open-ended and closed questions, while intrinsic motivation was tested with an adapted version of the Intrinsic Motivation Inventory (IMI). There were no differences in knowledge acquisition between the treatments. However, the results of the IMI showed significant differences in favour of the experimental group in interest/enjoyment, perceived competence, and perceived autonomy. Thus, living animals exert a positive influence on motivation.

  8. Bilateral upper limb trainer with virtual reality for post-stroke rehabilitation: case series report.

    PubMed

    Sampson, Michael; Shau, Yio-Wha; King, Marcus James

    2012-01-01

    Stroke is a leading cause of disability with many survivors having upper limb (UL) hemiparesis. UL rehabilitation using bilateral exercise enhances outcomes and the Bilateral Upper Limb Trainer (BUiLT) was developed to provide symmetrical, bilateral arm exercise in a 'forced' and self-assistive manner, incorporating virtual reality (VR) to provide direction and task specificity to users as well as action observation-execution and greater motivation to exercise. The BUiLT + VR system was trialled on five post-stroke participants with UL hemiparesis: one sub-acute and four chronic. The intervention was supplied for 45 min, 4 days/week for 6 weeks. The Fugl-Meyer Upper Extremity score (FMA-UE) was used as the primary outcome measure. Secondary outcome measures used were UL isometric strength and the Intrinsic Motivation Inventory (IMI) questionnaire. The BUiLT + VR therapy increased FMA-UE scores from 1 to 5 and overall strength in the shoulder and elbow. Motivation at the end of intervention was positive. Therapy using the BUiLT + VR system is reliable, can be administered safely and has a positive trend of benefit as measured by the FMA-UE, isometric strength testing and IMI questionnaire.

  9. Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

    PubMed

    Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

    2013-03-01

    Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

  10. Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3{NIT(C6H4OPh)}]: A μ+ spin relaxation study

    NASA Astrophysics Data System (ADS)

    Arosio, Paolo; Corti, Maurizio; Mariani, Manuel; Orsini, Francesco; Bogani, Lapo; Caneschi, Andrea; Lago, Jorge; Lascialfari, Alessandro

    2015-05-01

    The spin dynamics of the molecular magnetic chain [Dy(hfac)3{NIT(C6H4OPh)}] were investigated by means of the Muon Spin Relaxation (μ+SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac)3{NIT(C6H4OPh)}] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing μ+SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, two stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate λinterm(T), associated with the intermediate relaxing component. The experimental λinterm(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to τ = τ0 exp(Δ/kBT), corresponding to a distribution of energy barriers Δ. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state.

  11. A GIS-derived integrated moisture index to predict forest composition and productivity of Ohio forests (U.S.A.)

    Treesearch

    Louis R. Iverson; Martin E. Dale; Charles T. Scott; Anantha Prasad; Anantha Prasad

    1997-01-01

    A geographic information system (GIS) approach was used in conjunction with forest-plot data to develop an integrated moisture index (IMI), which was then used to predict forest productivity (site index) and species composition for forests in Ohio. In this region, typical of eastern hardwoods across the Midwest and southern Appalachians, topographic aspect and position...

  12. Command and Functional Analysis of the Intelligence Systems Architecture Assessment

    DTIC Science & Technology

    1991-06-01

    muwiemuc syaw m a sy be umddvSAEu£4C EdwiqpndmqiW orelw The *idn 7obptqmalajwemu Wiybe mWI ,s~ft du SARC Tar Rd ?)mu SM imV) .6 h, Sewndwy Ang Dkmu Sputeu...for bawatiug 0 To nuabsizi. qqmiar e fmr*g kwvguqe tawuatiwu and bateup’eatio aida and nabe rujwhwl topwl CDEC thdka 7. ESTABLISHMENT. A. IMiTIAMiN

  13. Department of Defense Interface Standard Electromagnetic Environmental Effects Requirements for Systems

    DTIC Science & Technology

    2002-12-19

    effective tool in evaluating IMI. A5.2.2 Shipboard internal electromagnetic environment (EME). For ship applications, electric fields (peak V/m-rms...effects waveform parameters ........................................ 9 MIL-STD-464A v CONTENTS Page TABLES 2B Electromagnetic fields from near...blasting of hardware. 3.8 Lightning indirect effects. Electrical transients induced by lightning due to coupling of electromagnetic fields . 3.9

  14. Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input

    PubMed Central

    Städele, Carola; Heigele, Stefanie; Stein, Wolfgang

    2015-01-01

    Stable rhythmic neural activity depends on the well-coordinated interplay of synaptic and cell-intrinsic conductances. Since all biophysical processes are temperature dependent, this interplay is challenged during temperature fluctuations. How the nervous system remains functional during temperature perturbations remains mostly unknown. We present a hitherto unknown mechanism of how temperature-induced changes in neural networks are compensated by changing their neuromodulatory state: activation of neuromodulatory pathways establishes a dynamic coregulation of synaptic and intrinsic conductances with opposing effects on neuronal activity when temperature changes, hence rescuing neuronal activity. Using the well-studied gastric mill pattern generator of the crab, we show that modest temperature increase can abolish rhythmic activity in isolated neural circuits due to increased leak currents in rhythm-generating neurons. Dynamic clamp-mediated addition of leak currents was sufficient to stop neuronal oscillations at low temperatures, and subtraction of additional leak currents at elevated temperatures was sufficient to rescue the rhythm. Despite the apparent sensitivity of the isolated nervous system to temperature fluctuations, the rhythm could be stabilized by activating extrinsic neuromodulatory inputs from descending projection neurons, a strategy that we indeed found to be implemented in intact animals. In the isolated nervous system, temperature compensation was achieved by stronger extrinsic neuromodulatory input from projection neurons or by augmenting projection neuron influence via bath application of the peptide cotransmitter Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia activates the modulator-induced current IMI (a nonlinear voltage-gated inward current) that effectively acted as a negative leak current and counterbalanced the temperature-induced leak to rescue neuronal oscillations. Computational modelling revealed the ability of IMI to reduce detrimental leak-current influences on neuronal networks over a broad conductance range and indicated that leak and IMI are closely coregulated in the biological system to enable stable motor patterns. In conclusion, these results show that temperature compensation does not need to be implemented within the network itself but can be conditionally provided by extrinsic neuromodulatory input that counterbalances temperature-induced modifications of circuit-intrinsic properties. PMID:26417944

  15. [Frequency of hypotrophic births in the Warsaw population].

    PubMed

    Pawlus, Beata; Wiśniewski, Andrzej

    2010-01-01

    Newborn's reduced body mass and length are regarded as an important symptom. The diagnosis requires careful observation of the individual's course of growth and metabolic condition. Various criteria are used to diagnose hypotrophy; 3rd, 5th or 10th percentile body mass are the most common, although others recommend using a value of -2.0 SDS body mass and length. To define the frequency of body mass and length deficiency in newborns in the Warsaw population. 4096 children born in single deliveries in 2009 at one Warsaw hospital. Body dimensions at birth were compared against the following standards, taking gestation period and sex into consideration: 1. Usher and McLean (UML). 2. A standard generally used in Warsaw maternity wards, drawn up by the Mother and Baby Institute (IMiD). 3. A standard drawn up in Wielkopolska (WLKP). Hypotrophy was diagnosed retrospectively on the basis of -2.0 SDS body mass and/or body length and 10th percentile body mass criterion. Regardless of sex and the standard being applied, at least one of the analysed body dimensions fell at or below -2.0 SDS in approximately 1% of all children. In newborn boys hypotrophy was diagnosed significantly less frequently using the UML standard than using the national ones, while in newborn girls it was diagnosed less frequently using the IMiD standard than UML or WLKP. Birth mass below the 10th percentile was found in approximately 7% and in just over 3% of all newborns using the IMiD and WLKP standards respectively. The absence of national standards for body length at birth makes the -2.0 SDS criterion difficult to use, while basing the diagnosis purely on evaluating body mass results in too few diagnoses of hypotrophy. Using the 10th percentile criterion allows for diagnosing hypotrophy in a few percent of newborns, while the Warsaw and Wielkopolska standards result in more diagnoses. Taking population trends into account, we postulate the need to prepare new national standards of body dimensions of newborns based on the gestation period.

  16. Antibiofilm and antibacterial effects of specific chitosan molecules on Staphylococcus aureus isolates associated with bovine mastitis

    PubMed Central

    Asli, Abdelhamid; Brouillette, Eric; Ster, Céline; Ghinet, Mariana Gabriela; Brzezinski, Ryszard; Lacasse, Pierre; Jacques, Mario

    2017-01-01

    Staphylococcus aureus is one of the major pathogens causing bovine intramammary infections (IMIs) and mastitis. Mastitis is the primary cause for the use of antibiotics in dairy farms but therapeutic failure is often observed. One of the reasons for the lack of effectiveness of antibiotic therapy despite the observed susceptibility of bacterial isolates in vitro are bacterial biofilms. In this study, we used chitosan of well-defined molecular weight (0.4–0.6, 1.3, 2.6 and 4.0 kDa) and investigated their antibiofilm and antibacterial activities in in vitro and in vivo models related to S. aureus IMIs. A chitosan of at least 6 units of glucosamine was necessary for maximum antibacterial activity. The 2.6 and 4.0 kDa forms were able to prevent biofilm production by the biofilm hyperproducer strain S. aureus 2117 and a bovine MRSA (methicillin-resistant S. aureus). The intramammary administration of the 2.6 kDa chitosan showed no adverse effects in mice or in cows, as opposed to the slight inflammatory effect observed in mammary glands with the 4.0 kDa derivative. The 2.6 kDa chitosan killed bacteria embedded in pre-established biofilms in a dose-dependent manner with a >3 log10 reduction in CFU at 4 mg/ml. Also, the 2.6 kDa chitosan could prevent the persistence of the internalized MRSA into the mammary epithelial cell line MAC-T. An in vitro checkerboard assay showed that the 2.6 kDa chitosan produced a synergy with the macrolide class of antibiotics (e.g., tilmicosin) and reduced the MIC of both molecules by 2–8 times. Finally, the intramammary administration of the 2.6 kDa chitosan alone (P<0.01) or in combination with tilmicosin (P<0.0001) reduced the colonization of mammary glands in a murine IMI model. Our results suggest that the use of chitosan alone or in combination with a low dose of a macrolide could help reduce antibiotic use in dairy farms. PMID:28486482

  17. Ka Hana `Imi Na`auao: A Science Curriculum Project

    NASA Astrophysics Data System (ADS)

    Napeahi, K.; Roberts, K. D.; Galloway, L. M.; Stodden, R. A.; Akuna, J.; Bruno, B.

    2005-12-01

    In antiquity, the first people to step foot on what are now known as the Hawaiian islands skillfully traversed the Pacific Ocean using celestial navigation and learned observations of scientific phenomena. Long before the Western world ventured beyond the horizon, Hawaiians had invented the chronometer, built aqueduct systems (awai) that continue to amaze modern engineers, and had preventive health systems as well as a comprehensive knowledge of medicinal plants (including antivirals) which only now are working their way through trials for use in modern pharmacopia. Yet, today, Native Hawaiians are severely underrepresented in science-related fields, reflecting (in part) a failure of the Western educational system to nurture the potential of these resourceful students, particularly the many "at-risk" students who are presently over-represented in special education. A curriculum which draws from and incorporates traditional Hawaiian values and knowledge is needed to reinforce links to the inquiry process which nurtured creative thinking during the renaissance of Polynesian history. The primary goal of the Ka Hana `Imi Na`auao Project (translation: `science` or `work in which you seek enlightenment, knowledge or wisdom`) is to increase the number of Native Hawaiian adults in science-related postsecondary education and employment fields. Working closely with Native Hawaiian cultural experts and our high school partners, we will develop and implement a culturally responsive 11th and 12th grade high school science curriculum, infused with math, literacy and technology readiness skills. Software and assistive technology will be used to adapt instruction to individual learners` reading levels, specific disabilities and learning styles. To ease the transition from secondary to post-secondary education, selected grade 12 students will participate in planned project activities that link high school experiences with college science-related programs of study. Ka Hana `Imi Na`auao is funded through a grant awarded to the University of Hawaii Center on Disability Studies (R.A. Stodden, PI) from the U.S. Department of Education, Native Hawaiian Education Act. Project information and curricula are available at http://www.scihi.hawaii.edu/.

  18. Heifers infected with coagulase-negative staphylococci in early lactation have fewer cases of clinical mastitis and higher milk production in their first lactation than noninfected heifers.

    PubMed

    Piepers, S; Opsomer, G; Barkema, H W; de Kruif, A; De Vliegher, S

    2010-05-01

    Intramammary infections (IMI) in recently calved dairy heifers are more common than was formerly believed but their relevance for future performance has been studied only rarely. In the present study, the association between the IMI status of fresh heifers and their subsequent udder health, milk production, and culling in first lactation was explored. Quarter milk samples were collected between 1 and 4 d in milk (DIM) and between 5 and 8 DIM from 191 dairy heifers in 20 dairy herds for bacteriological culturing and somatic cell count (SCC) analysis. Monthly milk recording data including composite milk SCC and test-day milk yield (MY) were obtained for the first 285 DIM or until culling. Farmer-recorded clinical mastitis cases were available. Data were analyzed using mixed models and survival analysis. Approximately 80% of the fresh heifers (79.8%) had at least one culture-positive quarter. Coagulase-negative staphylococci (CNS) were the most frequently isolated pathogens (72%), followed by esculin-positive streptococci (4.6%) and Staphylococcus aureus (3.5%). Overall geometric mean SCC at quarter level decreased between the first and second samplings from 348,000 to 116,000 cells/mL. Heifers infected with CNS had an intermediate average test-day SCC (84,000 cells/mL) during the first 285 DIM compared with noninfected heifers (53,000 cells/mL) and heifers infected with major pathogens (195,000 cells/mL). Heifers infected with major pathogens had a much lower average daily MY (18.3kg) during first lactation compared with noninfected animals (21.3kg). That CNS-infected heifers out-produced their noninfected counterparts could be at least partially explained by their significantly lower incidence of clinical mastitis (incidence risk 3.6 vs. 21.0%) during first lactation compared with noninfected heifers. We conclude that although CNS cause the majority of IMI in heifers around calving, they should not be a reason for serious concern. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Whole Genome Sequencing of Fusarium fujikuroi Provides Insight into the Role of Secretory Proteins and Cell Wall Degrading Enzymes in Causing Bakanae Disease of Rice

    PubMed Central

    Bashyal, Bishnu M.; Rawat, Kirti; Sharma, Sapna; Kulshreshtha, Deepika; Gopala Krishnan, S.; Singh, Ashok K.; Dubey, Himanshu; Solanke, Amolkumar U.; Sharma, T. R.; Aggarwal, Rashmi

    2017-01-01

    Fusarium fujikuroi causing bakanae disease has emerged as one of the major pathogen of rice across the world. The study aims to comparative genomic analysis of Fusarium fujikuroi isolates and identification of the secretary proteins of the fungus involved in rice pathogenesis. In the present study, F. fujikuroi isolate “F250” was sequenced with an assembly size of 42.47 Mb providing coverage of 96.89% on reference IMI58289 genome. A total of 13,603 protein-coding genes were predicted from genome assembly. The average gene density in the F. fujikuroi genome was 315.10 genes per Mb with an average gene length of 1.67 kb. Additionally, 134,374 single nucleotide polymorphisms (SNPs) are identified against IMI58289 isolate, with an average SNP density of 3.11 per kb of genome. Repetitive elements represent approximately 270,550 bp, which is 0.63% of the total genome. In total, 3,109 simple sequence repeats (SSRs), including 302 compound SSRs are identified in the 8,656 scaffolds. Comparative analysis of the isolates of F. fujikuroi revealed that they shared a total of 12,240 common clusters with F250 showing higher similarity with IMI58289. A total of 1,194 secretory proteins were identified in its genome among which there were 356 genes encoding carbohydrate active enzymes (CAZymes) capable for degradation of complex polysaccharides. Out of them glycoside hydrolase (GH) families were most prevalent (41%) followed by carbohydrate esterase (CE). Out of them CE8 (4 genes), PL1 (10 genes), PL3 (5 genes), and GH28 (8 genes) were prominent plant cell wall degrading enzymes families in F250 secretome. Besides this, 585 genes essential for the pathogen–host interactions were also identified. Selected genes were validated through quantitative real-time PCR analyses in resistant and susceptible genotypes of rice at different days of inoculation. The data offers a better understanding of F. fujikuroi genome and will help us enhance our knowledge on Fusarium fujikuroi–rice interactions. PMID:29230233

  20. A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan

    PubMed Central

    Ohori, Manami; Inagaki, Yusuke; Shimooka, Yuko; Sugimura, Naoya; Ishihara, Ikuyo; Yoshida, Tomotaka

    2018-01-01

    The individualized occupational therapy (IOT) program is a psychosocial program that we developed to facilitate proactive participation in treatment and improve cognitive functioning and other outcomes for inpatients with acute schizophrenia. The program consists of motivational interviewing, self-monitoring, individualized visits, handicraft activities, individualized psychoeducation, and discharge planning. This multicenter, open-labeled, blinded-endpoint, randomized controlled trial evaluated the impact of adding IOT to a group OT (GOT) program as usual for outcomes in recently hospitalized patients with schizophrenia in Japanese psychiatric hospitals setting compared with GOT alone. Patients with schizophrenia were randomly assigned to the GOT+IOT group or the GOT alone group. Among 136 randomized patients, 129 were included in the intent-to-treat population: 66 in the GOT+IOT and 63 in the GOT alone groups. Outcomes were administered at baseline and discharge or 3 months following hospitalization including the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J), the Schizophrenia Cognition Rating Scale Japanese version, the Social Functioning Scale Japanese version, the Global Assessment of Functioning scale, the Intrinsic Motivation Inventory Japanese version (IMI-J), the Morisky Medication Adherence Scale-8 (MMAS-8), the Positive and Negative Syndrome Scale (PANSS), and the Japanese version of Client Satisfaction Questionnaire-8 (CSQ-8J). Results of linear mixed effects models indicated that the IOT+GOT showed significant improvements in verbal memory (p <0.01), working memory (p = 0.02), verbal fluency (p < 0.01), attention (p < 0.01), and composite score (p < 0.01) on the BACS-J; interest/enjoyment (p < 0.01), value/usefulness (p < 0.01), perceived choice (p < 0.01), and IMI-J total (p < 0.01) on the IMI-J; MMAS-8 score (p < 0.01) compared with the GOT alone. Patients in the GOT+IOT demonstrated significant improvements on the CSQ-8J compared with the GOT alone (p < 0.01). The present findings provide support for the feasibility in implementing an IOT program and its effectiveness for improving cognitive impairment and other outcomes in patients with schizophrenia. PMID:29621261

  1. A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan.

    PubMed

    Shimada, Takeshi; Ohori, Manami; Inagaki, Yusuke; Shimooka, Yuko; Sugimura, Naoya; Ishihara, Ikuyo; Yoshida, Tomotaka; Kobayashi, Masayoshi

    2018-01-01

    The individualized occupational therapy (IOT) program is a psychosocial program that we developed to facilitate proactive participation in treatment and improve cognitive functioning and other outcomes for inpatients with acute schizophrenia. The program consists of motivational interviewing, self-monitoring, individualized visits, handicraft activities, individualized psychoeducation, and discharge planning. This multicenter, open-labeled, blinded-endpoint, randomized controlled trial evaluated the impact of adding IOT to a group OT (GOT) program as usual for outcomes in recently hospitalized patients with schizophrenia in Japanese psychiatric hospitals setting compared with GOT alone. Patients with schizophrenia were randomly assigned to the GOT+IOT group or the GOT alone group. Among 136 randomized patients, 129 were included in the intent-to-treat population: 66 in the GOT+IOT and 63 in the GOT alone groups. Outcomes were administered at baseline and discharge or 3 months following hospitalization including the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J), the Schizophrenia Cognition Rating Scale Japanese version, the Social Functioning Scale Japanese version, the Global Assessment of Functioning scale, the Intrinsic Motivation Inventory Japanese version (IMI-J), the Morisky Medication Adherence Scale-8 (MMAS-8), the Positive and Negative Syndrome Scale (PANSS), and the Japanese version of Client Satisfaction Questionnaire-8 (CSQ-8J). Results of linear mixed effects models indicated that the IOT+GOT showed significant improvements in verbal memory (p <0.01), working memory (p = 0.02), verbal fluency (p < 0.01), attention (p < 0.01), and composite score (p < 0.01) on the BACS-J; interest/enjoyment (p < 0.01), value/usefulness (p < 0.01), perceived choice (p < 0.01), and IMI-J total (p < 0.01) on the IMI-J; MMAS-8 score (p < 0.01) compared with the GOT alone. Patients in the GOT+IOT demonstrated significant improvements on the CSQ-8J compared with the GOT alone (p < 0.01). The present findings provide support for the feasibility in implementing an IOT program and its effectiveness for improving cognitive impairment and other outcomes in patients with schizophrenia.

  2. 40-year trends in meal and snack eating behaviors of American adults.

    PubMed

    Kant, Ashima K; Graubard, Barry I

    2015-01-01

    Understanding changes in profiles of eating behaviors over time may provide insights into contributors to upward trajectories of obesity in the US population. Yet little is known about whether or not characteristics of meal and snack eating behaviors reported by adult Americans have changed over time. To examine time trends in the distribution of day's intake into individual meal and snack behaviors and related attributes in the US adult population. The study was observational with cross-sectional data from national surveys fielded over 40 years. Nationally representative dietary data from nine National Health and Nutrition Examination Surveys conducted from 1971-1974 to 2009-2010 (N=62,298 participants aged 20-74 years) were used to describe eating behaviors. The respondent-labeled eating behaviors examined included main meals (breakfast, lunch, and dinner), and snacks (before breakfast, between breakfast and lunch, between lunch and dinner, after dinner, or other). For each eating behavior, percent of reporters, relative contribution to 24-hour energy intake, the clock time of report, and intermeal/snack intervals were examined. Multivariable logistic and linear regression methods for analysis of complex survey data adjusted for characteristics of respondents in each survey. Over the 40-year span examined reports of each individual named main meal (or all three main meals) declined, but reports of only two out of three meals or the same meal more than once increased; the percentage of 24-hour energy from snacks reported between lunch and dinner or snacks that displaced meals increased; clock times of breakfast and lunch were later, and intervals between dinner and after-dinner snack were shorter. Changes in several snack reporting behaviors (eg, report of any snack or ≥2 snacks), were significant in women only. Several meal and snack eating behaviors of American adults changed over time, with a greater change in snack behaviors of women relative to men. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  3. 40-year trends in meal and snack eating behaviors of American adults

    PubMed Central

    Kant, Ashima K.; Graubard, Barry I.

    2014-01-01

    Background Understanding of changes in profiles of eating behaviors over time may provide insights into contributors to upward trajectories of obesity in the United States population. Yet, little is known about whether characteristics of meal and snack eating behaviors reported by adult Americans have changed over time. Objective This study examined time trends in the distribution of day’s intake into individual meal and snack behaviors and related attributes in the United States adult population. Design The study was observational with cross-sectional data from national surveys fielded over 40 years. Participant/setting Nationally representative dietary data from nine National Health and Nutrition Examination Surveys conducted from 1971–74 to 2009–2010 (n=62298; age 20–74 years) were used to describe eating behaviors. Outcomes examined The respondent-labeled eating behaviors examined included main meals (breakfast, lunch, and dinner), and snacks (before breakfast, between breakfast and lunch, between lunch and dinner, after dinner, or other). For each eating behavior, percent of reporters; relative contribution to 24-hour energy intake; the clock time of report; and intermeal/snack intervals were examined. Statistical Analysis Multivariable logistic and linear regression methods for analysis of complex survey data adjusted for characteristics of respondents in each survey. Results Over the 40-year span examined: 1) reports of each individual named main meal (or all three main meals) declined, but reports of only two out of three meals or the same meal more than once increased; 2) the percentage of 24-hour energy from snacks reported between lunch and dinner or snacks that displaced meals increased; 3) clock times of breakfast and lunch were later, and intervals between dinner and after dinner snack were shorter. Changes in several snack reporting behaviors (e.g., report of any snack or ≥2 snacks), were significant in women only. Conclusions Several meal and snack eating behaviors of American adults changed over time, with a greater change in snack behaviors of women relative to men. PMID:25088521

  4. Angular Motion of Projectiles with a Moving Internal Part.

    DTIC Science & Technology

    1977-02-01

    Ball Rotor T317 hellIntermal Projectile RingsM505 Fuze Quasi-linear Angular Motion N\\ ANSTRACT (-jCanhs si rveree side ff naeweemv end identify by...LIST OF FIGURES Figure Page 1. 20mm Shell T282E1 with Arming Ball Rotor .... .......... 20 2. Fast Mode Damping Rate for the 20mm T282E1...fuze has a spherical arming rotor in a cylindrical cavity with small but non-zero clearanc’es (Figure 1). The fourth sa.ell - the 8-inch T317 - showed

  5. The "Intentionality Measurement Instrument" [or "IMI"]: A Comprehensive Psychometric Instrument Based upon the Dual Quadrant Scalar Model of Intentionality That Is Designed to Measure Intent, Motive Type, and Disposition

    ERIC Educational Resources Information Center

    Osler, James Edward, II

    2016-01-01

    The overall aim of this paper is to provide an epistemological rational for the measurement of intentionality. The purpose of this narrative is to identify "Intentionality" as an arena of action in the dispositional learning domain can be measured using an "Intentionality Measurement Instrument" [also referred by the acronym…

  6. New Tools and Metrics for Evaluating Army Distributed Learning

    DTIC Science & Technology

    2011-01-01

    courseware. Designing DL to provide for more opportunities for interaction with instructors and peers is likely to increase student engagement in IMI...toward blended learning may achieve these goals. Student engagement may also be fostered to the extent that the course pro- vides sufficient numbers of... student engagement . • Design and implement DL in ways that provide greater opportunities to interact with instructors and peers. • Enforce policy of

  7. Integrated Maintenance Information System (IMIS) Diagnostic Module Redesign

    DTIC Science & Technology

    1990-12-01

    Government- related procurement, the United States Government incurs no responsibility or any obligation whatsoever. The fact that the Government may have...invention that may in any way be related thereto. The Public Affairs Office has reviewed this report, and it is releasable to the National Technical...instance of the controller class is needed to perform diagnostics. This instance creates, monitors, and controls one or more diagnostic groups . This process

  8. Performance Assessment Tools for Distance Learning and Simulation: Knowledge, Models and Tools to Improve the Effectiveness of Naval Distance Learning

    DTIC Science & Technology

    2006-06-01

    34/> <!-- someapplet.imi -- > <property narne="appletcontent"’ value="somecontent jar"!> <!- - someapplet.lml -- > <property narne="jnlpcodebasedir" value= gizmo "!> gizmo ...property name="jnlphref"’ value="gizmo.jnlp",’> 0!- - gizmo.jnlp -- > <property narne="jnlptitle"’ value="Nifty Gizmo !/> <!-- nifty gizmo

  9. Effects of repeated prescribed fires on the structure, composition, and regeneration of mixed-oak forests in Ohio

    Treesearch

    Todd F. Hutchinson; Elaine Kennedy Sutherland; Daniel A. Yaussy

    2005-01-01

    This study quantifies prescribed fire effects at four sites in southern Ohio, from 1995 to 2002. Each site had three treatment units: an unburned control, a unit burned 2x (1996 and 1999), and a unit burned 4 x (1996-1999). Vegetation plots were stratified by an integrated moisture index (IMI) into xeric, intermediate, and mesic classes. Prior to treatments, oak (...

  10. Interactive Multimedia Instruction for Training Self-Directed Learning Techniques

    DTIC Science & Technology

    2016-06-01

    feedback and input on the content, format, and pedagogical approach of the lesson. This survey could be e-mailed to the principal ARI researcher for...peers in self-directed learning. Some examples of the metaphorical relationships and common examples woven into this IMI are identified in Table 1...20 Table 1 Metaphorical Relationships and Illustrations Used in Self-Directed Learning Training Military or Common Example Self-Directed

  11. Interaction between Water Borne Waves and Seismic Waves in the Ocean Bottom: The Forward- and Inverse Problem,

    DTIC Science & Technology

    1986-04-15

    Petroleum Directorate for supplying- and giving consent to publish the shot data. The financial travel support given by the Royal Norwegian Council for...9i 4CY - 30 o 0 0 0 0 0 0 A 0 0 0 0 140R. 4AVENUMERC i/Mi Figure 3. 17: F-k diagram for shot number 100. A: surfi.sc ,nt linear salp

  12. Integrated Maintenance Information System (IMIS): A Maintenance Information Delivery Concept.

    DTIC Science & Technology

    1987-11-01

    InterFace Figure 2. Portable Maintenance Computer Concept. provide advice for difficult fault-isolation problems . The technician will be able to accomplish...faced with an ever-growing number of paper-based technical orders (TOs). This has greatly increased costs and distribution problems . In addition, it has...compounded problems associ- ated with ensuring accurate data and the lengthy correction times involved. To improve the accuracy of technical data and

  13. 78 FR 63570 - Proposed Collection; Comment Request for Forms W-8BEN, W-8BEN-E, W-8ECI, W-8EXP, and W-8IMY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... Owner for United States Tax Withholding, Form W-8BEN-E, Certificate of Status of Beneficial Owner for United States Tax Withholding, Form W-8ECI, Certificate of Foreign Person's Claim for Exemption From Withholding on Income Effectively Connected With the Conduct of a Trade or Business in the United States, Form...

  14. Characterization of a genetically distinct subpopulation of Staphylococcus haemolyticus isolated from milk of cows with intramammary infections.

    PubMed

    Wanecka, Anna; Król, Jarosław; Twardoń, Jan; Mrowiec, Jacek; Bania, Jacek; Korzeniowska-Kowal, Agnieszka; Tobiasz, Anna

    2018-02-01

    The aim of this paper is to describe a novel subpopulation of Staphylococcus haemolyticus isolated from intramammary gland infections (IMI) in cattle. In total, eight isolates originating from milk samples from two unrelated dairy farms were examined phenotypically (using the ID 32 STAPH system) and genotypically. These isolates had almost identical sequences of each of the housekeeping genes examined (dnaJ, rpoB and sodA) but these sequences displayed similarity of only ∼92.5%, 95.0% and 96.8%, respectively, with known S. haemolyticus sequences. The atypical isolates could also be distinguished biochemically by the positive β-galactosidase test (with 2-naphthyl-β-d-galactopyranoside as the substrate). All the isolates were identified as S. haemolyticus upon MALDI-TOF analysis but half of them, that achieved scores 1.7-1.999 (not reliable species identification), required expanding the commercial database for secure identification. Our study has shown that IMI in cattle may be caused by two distinct subpopulations of S. haemolyticus, differing clearly by some genotypic and phenotypic properties. The first of these subpopulations seems to be common to many hosts (including humans), whereas the second (possibly at the subspecies rank) is, so far, found only in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. [The clinical effectiveness of a post milking teat disinfection method with a foaming iodophor teat dip].

    PubMed

    Falkenberg, U; Tenhagen, B A; Heuwieser, W; Kalbe, P; Klünder, G; Baumgärtner, B

    2003-02-01

    The effect of postmilking teat dipping with a foaming iodophor agent on incidence of intramammary infections (IMI), incidence of clinical mastitis, somatic cell count and the characteristics of udder tissue and teat was investigated in a positively controlled field study. Two groups of animals were compared. Teats were dipped with a foaming iodophor in the treatment group (TG, 122 animals) while teats in the control group (CG, 121 animals) were dipped with a conventional iodophor teat dip with the same iodine content. A bacteriological examination of quarter milk samples divided the study period in two parts. The incidence of new IMI did not differ between the groups (1st part of trial: TG vs. CG: 6.84% vs. 9.16%, 2nd part of trial: 7.78% vs. 7.82%). There were no differences between the treatment groups regarding incidence of clinical mastitis. We detected 0.64 clinical cases per 100 days in the treatment group vs. 0.50 in the control group. The development of SCC was comparable in both groups. Teat skin and teat duct conditions showed variation during the study period. Clinical efficacy of postmilking teat disinfection with a foaming iodophor was comparable to the treatment with a conventional iodophor product.

  16. The Benefits of Mouse Keeping—an Empirical Study on Students' Flow and Intrinsic Motivation in Biology Lessons

    NASA Astrophysics Data System (ADS)

    Meyer, Annika; Klingenberg, Konstantin; Wilde, Matthias

    2016-02-01

    Contact with living animals is an exceptional possibility within biology education to facilitate an intense immersion into the study topic and even allow for a flow experience (Csikszentmihalyi 2000). Further, it might affect the perceptions of the students' basic needs for autonomy and competence and thereby their quality of motivation (Deci and Ryan 1985, 2002). Still, there is little empirical evidence about the duration of the exposure with living animals that is required. We investigated the students' flow experience, and the students' motivation, reported retrospectively in three different treatments: lessons involving short-term or long-term contact with living harvest mice and a control group without living animals. Our sample consisted of 156 fifth graders (10.76 years, SD = 0.513). The test instruments were adapted versions of the Flow Short Scale (FSS, Rheinberg et al. 2003) and of the Intrinsic Motivation Inventory (IMI, Ryan 1982). As expected, the control group produced significantly lower scores for both FSS and IMI. In addition, we found a significant difference between students with short-term versus long-term contact. Whereas the flow experience was indistinguishable for all pupils who had contact with living animals, those with long-term experience reported significantly higher intrinsic motivation.

  17. Efficacy of recombinant bovine epidermal growth factor in the treatment of experimental subclinical Staphylococcus aureus mastitis in a ewe model.

    PubMed

    Gabadage, Kamal; Chirino-Trejo, Manuel; Campbell, John; Luby, Christopher

    2017-01-01

    Staphylococcus aureus is the most common contagious mastitis pathogen of dairy cattle. Antimicrobial treatment of infected cattle results in variable cure rates. Epidermal growth factor (EGF) plays an important role in the modulation of host innate immune responses and the regulation of mammary epithelial regeneration, indicating that EGF may be useful as a treatment for mastitis. A pilot study was conducted to evaluate the efficacy of recombinant bovine EGF (rbEGF) for the treatment of S aureus intramammary infection (IMI) using an ovine model. Each ewe was experimentally infected with S aureus in both udder halves. One udder half of each ewe received one of two treatments: EGF (n=13) or pirlimycin (n=13). The contralateral udder half of each ewe received sterile saline as a control. The bacteriological cure rate following rbEGF was significantly lower (15 per cent) than that attained with pirlimycin hydrochloride (61 per cent) and did not differ from that following treatment with sterile saline. Cure rates following treatment with rbEGF were not significantly different to those following sterile saline. Given that EGF is associated with modulation of host immunity and wound healing, future studies into EGF should not focus on whether EGF increases cure rates of S aureus IMI.

  18. mirPub: a database for searching microRNA publications.

    PubMed

    Vergoulis, Thanasis; Kanellos, Ilias; Kostoulas, Nikos; Georgakilas, Georgios; Sellis, Timos; Hatzigeorgiou, Artemis; Dalamagas, Theodore

    2015-05-01

    Identifying, amongst millions of publications available in MEDLINE, those that are relevant to specific microRNAs (miRNAs) of interest based on keyword search faces major obstacles. References to miRNA names in the literature often deviate from standard nomenclature for various reasons, since even the official nomenclature evolves. For instance, a single miRNA name may identify two completely different molecules or two different names may refer to the same molecule. mirPub is a database with a powerful and intuitive interface, which facilitates searching for miRNA literature, addressing the aforementioned issues. To provide effective search services, mirPub applies text mining techniques on MEDLINE, integrates data from several curated databases and exploits data from its user community following a crowdsourcing approach. Other key features include an interactive visualization service that illustrates intuitively the evolution of miRNA data, tag clouds summarizing the relevance of publications to particular diseases, cell types or tissues and access to TarBase 6.0 data to oversee genes related to miRNA publications. mirPub is freely available at http://www.microrna.gr/mirpub/. vergoulis@imis.athena-innovation.gr or dalamag@imis.athena-innovation.gr Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  19. Candida keroseneae sp. nov., a novel contaminant of aviation kerosene.

    PubMed

    Buddie, A G; Bridge, P D; Kelley, J; Ryan, M J

    2011-01-01

    To characterize and identify a novel contaminant of aviation fuel. Micro-organisms (yeasts and bacteria) were isolated from samples of aviation fuel. A yeast that proved to have been unrecorded previously was isolated from more than one fuel sample. This novel yeast proved to be a new species of Candida and is described here. Ribosomal RNA gene sequence analyses of internal transcribed spacer (ITS) regions (including 5·8S subunit) plus the 26S D1/D2 domains showed the strains to cluster within the Candida membranifaciens clade nearest to, but distinct from, Candida tumulicola. Phenotypic tests were identical for both isolates. Physiological and biochemical tests supported their position as a separate taxon. The yeast was assessed for its effect on the main constituent hydrocarbons of aviation fuel. Two strains (IMI 395605(T) and IMI 395606) belonging to the novel yeast species, Candida keroseneae, were isolated from samples of aircraft fuel (kerosene), characterized and described herein with reference to their potential as contaminants of aviation fuel. As a result of isolating a novel yeast from aviation fuel, the implications for microbial contamination of such fuel should be considered more widely than previously thought. © 2010 CAB International. Letters in Applied Microbiology © 2010 The Society for Applied Microbiology.

  20. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    PubMed

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  1. IMIS: An intelligence microscope imaging system

    NASA Technical Reports Server (NTRS)

    Caputo, Michael; Hunter, Norwood; Taylor, Gerald

    1994-01-01

    Until recently microscope users in space relied on traditional microscopy techniques that required manual operation of the microscope and recording of observations in the form of written notes, drawings, or photographs. This method was time consuming and required the return of film and drawings from space for analysis. No real-time data analysis was possible. Advances in digital and video technologies along with recent developments in article intelligence will allow future space microscopists to have a choice of three additional modes of microscopy: remote coaching, remote control, and automation. Remote coaching requires manual operations of the microscope with instructions given by two-way audio/video transmission during critical phases of the experiment. When using the remote mode of microscopy, the Principal Investigator controls the microscope from the ground. The automated mode employs artificial intelligence to control microscope functions and is the only mode that can be operated in the other three modes as well. The purpose of this presentation is to discuss the advantages and disadvantages of the four modes of of microscopy and how the IMIS, a proposed intelligent microscope imaging system, can be used as a model for developing and testing concepts, operating procedures, and equipment design of specifications required to provide a comprehensive microscopy/imaging capability onboard Space Station Freedom.

  2. A brief review of salient factors influencing adult eating behaviour.

    PubMed

    Emilien, Christine; Hollis, James H

    2017-12-01

    A better understanding of the factors that influence eating behaviour is of importance as our food choices are associated with the risk of developing chronic diseases such as obesity, CVD, type 2 diabetes or some forms of cancer. In addition, accumulating evidence suggests that the industrial food production system is a major contributor to greenhouse gas emission and may be unsustainable. Therefore, our food choices may also contribute to climate change. By identifying the factors that influence eating behaviour new interventions may be developed, at the individual or population level, to modify eating behaviour and contribute to society's health and environmental goals. Research indicates that eating behaviour is dictated by a complex interaction between physiology, environment, psychology, culture, socio-economics and genetics that is not fully understood. While a growing body of research has identified how several single factors influence eating behaviour, a better understanding of how these factors interact is required to facilitate the developing new models of eating behaviour. Due to the diversity of influences on eating behaviour this would probably necessitate a greater focus on multi-disciplinary research. In the present review, the influence of several salient physiological and environmental factors (largely related to food characteristics) on meal initiation, satiation (meal size) and satiety (inter-meal interval) are briefly discussed. Due to the large literature this review is not exhaustive but illustrates the complexity of eating behaviour. The present review will also highlight several limitations that apply to eating behaviour research.

  3. Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3(NIT(C6H4OPh))]: A μ{sup +} spin relaxation study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arosio, Paolo, E-mail: paolo.arosio@guest.unimi.it; Orsini, Francesco; Corti, Maurizio

    2015-05-07

    The spin dynamics of the molecular magnetic chain [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] were investigated by means of the Muon Spin Relaxation (μ{sup +}SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing μ{sup +}SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, twomore » stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate λ{sub interm}(T), associated with the intermediate relaxing component. The experimental λ{sub interm}(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to τ = τ{sub 0} exp(Δ/k{sub B}T), corresponding to a distribution of energy barriers Δ. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state.« less

  4. A Comparison of Interactive Multimedia Instruction Designs Addressing Soldiers Learning Needs

    DTIC Science & Technology

    2016-03-01

    tailored training group would have higher point gains from pretest to posttest for the less familiar content domain (Adjust Indirect Fire) compared to...and posttest scores and user experiences, a correlation analysis was conducted. Soldiers who tended to have higher scores on the pretest also had...Soldiers enrolled in the Warrior Leaders Course at Fort Benning, GA. All the IMI variations were associated with increased test scores on posttests , but

  5. The Prospects for Increasing the Reuse of Digital Training Content

    DTIC Science & Technology

    2009-01-01

    reuse, and using mandates or financial pressure to stimulate reuse. One mechanism for addressing incentive issues is the high- level directive that...the average cost of developing interactive multimedia instruction (IMI), level 2–3,2 in 2007 was $24,700 (Brandon Hall Research, 2007). The 1 One... Level refers to “ levels of interactivity” between the learner and DL media, with higher levels involving more learner participation. Levels of

  6. Designing Interactive Multimedia Instruction to Address Soldiers’ Learning Needs

    DTIC Science & Technology

    2014-12-01

    A point of need design seeks to identify and meet specific learning needs. It does so by focusing on the learning needs of an identified group ...instructional design and tailored training techniques to address the Army Learning Model (ALM) point of need concept. The point of need concept focuses both on ...developing six IMI exemplars focused on point of need training, including three variations of needs-focused designs : familiarization, core, and tailored

  7. Radiation Effects on Transmission in Optical Fiber Systems.

    DTIC Science & Technology

    1981-06-02

    TRANSMSSION - ~IN OPTCAL FIBE SYSTEMS UMATED STATE NAVAL ACADEMY * ANNAPOLIS, MARYLAND * 1981 * -~~ Thm dooummt bus bur apwgd hi pubic AWNm mi Imi it dlbutlou...nanometers. Of the fibers studied, two were high purity silica fibers. An important result of the study was that the radiation induced damage was...wavelength related. The induced damage decreased rapidly as the wavelength increased from 800 to 1100 nanometers, with minimal damage noted above 1300

  8. FY83 Posture Report: Research, Development, Engineering and Acquisition.

    DTIC Science & Technology

    1983-01-01

    to provide staff management and con- fluids, corrosion preventives, chemistry , chemical trol of Belvoir R&D Center’s force structure through the...vialiing boith FV82 antI FY83 fundsi. Early mianagenlerit r atar refletotrs anti c4tint racting fair sei-imi-generat itir iietlingp estabrlisliedi the phi...ft) to accommodate boats such as the fabrics. paper chemistry , preservatives, fuels, optical LCU, LCM-8. Ribbon Bridge Erection Boat, Small Tug. and

  9. EEG topography and tomography (LORETA) in diagnosis and pharmacotherapy of depression.

    PubMed

    Saletu, B; Anderer, P; Saletu-Zyhlarz, G M

    2010-10-01

    Earlier investigations suggested an involvement of the right hemisphere and the left prefrontal cortex (PFC) in the pathogenesis of depression. This paper presents our own electroencephalographic (EEG) topography and low-resolution brain electromagnetic tomography (LORETA) data obtained in unmedicated depressed patients, and the effects of two representative drugs of non-sedative and sedative antidepressants, i.e., citalopram (CIT) and imipramine (IMI), as compared with placebo in normal subjects. Sixty female menopausal syndrome patients with the diagnosis of a depressive episode without psychotic symptoms as well as 30 healthy controls were investigated. Concerning the effects of antidepressants, normal healthy subjects received single oral doses of 20 mg CIT, 75 mg IMI and placebo p.o. A 3-min vigilance-controlled EEG and a 4-min resting EEG was recorded pre- and post-drug administration and analyzed by means of EEG mapping and LORETA. In the EEG mapping, depressed patients demonstrated a decrease in absolute power in all frequency bands, an augmentation of relative delta/theta and beta and a decrease in alpha activity as well as a slowing of the delta/theta centroid and an acceleration of the alpha and beta centroid, which suggests vigilance decrements. In the alpha asymmetry index, they showed right frontal hyper- and left frontal hypoactivation correlated with the Hamilton Depression Score (HAMD). LORETA predominantly revealed decreased power in the theta and alpha-1 frequency band. Negative correlations between theta power and the HAMD were observed in the ventro-medial PFC, the bilateral rostral anterior cingulate cortex (ACC) and the left insular cortex; between alpha-1 power and the HAMD in the right PFC. In the EEG mapping of antidepressants, 20 mg CIT showed mainly activating, 75 mg IMI partly sedative properties. LORETA revealed that CIT increased alpha-2, beta-1, beta-2 and beta-3 power more over the right than over the left hemisphere. However, also a left temporal and frontal delta increase was observed. In conclusion, EEG topography and tomography of depressed menopausal patients demonstrated a right frontal hyper- and left frontal hypoactivation in the alpha asymmetry index as well as a vigilance decrease, with a right-hemispheric preponderance. Within antidepressants at least 2 subtypes may be distinguished from the electrophysiological point of view, a non-sedative and a sedative. LORETA identifies cerebral generators responsible for the pathogenesis of depression as well as for the mode of action of antidepressants.

  10. Routine determination of sulfonylurea, imidazolinone, and sulfonamide herbicides at nanogram-per-liter concentrations by solid-phase extraction and liquid chromatography/mass spectrometry

    USGS Publications Warehouse

    Furlong, E.T.; Burkhardt, M.R.; Gates, Paul M.; Werner, S.L.; Battaglin, W.A.

    2000-01-01

    Sulfonylurea (SU), imidazolinone (IMI), and sulfonamide (SA) herbicides are new classes of low-application-rate herbicides increasingly used by farmers. Some of these herbicides affect both weed and crop species at low dosages and must be carefully used. Less is known about the effect of these compounds on non-crop plant species, but a concentration of 100 ng/l in water has been proposed as the threshold for possible plant toxicity for most of these herbicides. Hence, analytical methods must be capable of detecting SUs, IMIs, and SAs at concentrations less than 100 ng/l in ambient water samples. The authors developed a two-cartridge, solid-phase extraction method for isolating 12 SU, 3 IMI, and 1 SA herbicides by using high-performance liquid chromatography/electrospray ionization-mass spectrometry (HPLC/ESI-MS) to identify and quantify these herbicides to 10 ng/l. This method was used to analyze 196 surface- and ground-water samples collected from May to August 1998 throughout the Midwestern United States, and more than 100 quality-assurance and quality-control samples. During the 16 weeks of the study, the HPLC/ESI-MS maintained excellent calibration linearity across the calibration range from 5 to 500 ng/l, with correlation coefficients of 0.9975 or greater. Continuing calibration verification standards at 100-ng/l concentration were analyzed throughout the study, and the average measured concentrations for individual herbicides ranged from 93 to 100 ng/l. Recovery of herbicides from 27 reagent-water samples spiked at 50 and 100 ng/l ranged from 39 to 92%, and averaged 73%. The standard deviation of recoveries ranged from 14 to 26%, and averaged 20%. This variability reflects multiple instruments, operators, and the use of automated and manual sample preparation. Spiked environmental water samples had similar recoveries, although for some herbicides, the sample matrix enhanced recoveries by as much as 200% greater than the spiked concentration. This matrix enhancement was sample- and compound-dependent. Concentrations of herbicides in unspiked duplicate environmental samples were typically within 25% of each other. The results demonstrate the usefulness of HPLC/ESI-MS for determining low-application-rate herbicides at ambient concentrations. Copyright (C) 2000 Elsevier Science B.V.

  11. Whole-genome sequence of the orchid anthracnose pathogen Colletotrichum orchidophilum.

    PubMed

    Baroncelli, Riccardo; Sukno, Serenella; Sarrocco, Sabrina; Cafà, Giovanni; Le Floch, Gaetan; Thon, Michael R

    2018-04-12

    Colletotrichum orchidophilum is a plant pathogenic fungus infecting a wide range of plant species belonging to the family Orchidaceae. Besides its economic impact, C. orchidophilum has been used in recent years in evolutionary studies as it represents the closest related species to the C. acutatum species complex. Here we present the first draft whole-genome sequence of C. orchidophilum IMI 309357, providing a resource for future research on anthracnose of Orchidaceae and other hosts.

  12. Archaeological Test Sampling of Sites within the La Quinta Flood Control Channel Easement,

    DTIC Science & Technology

    1980-03-01

    J L CRAIB MAR 80UNCLASSIFIED DACW@9-80-M-0975 F/G 5/6 NL | EmhhhhhhommhhlmEEIE hhhhhl I E5Ehhhhhhhhlh IIllfllfflfflffllfllf U-IIIIII a J 12 !EM imi.I...ima ii~ti -- I .u 1111125 11114 111116 MICROCOPY RESOLUTION TEST CHART NATIONAL BUR.AU OF STANDARDS-1963- A K- Lo’ • ~ ~ ~ ~ ~ ~ ~ ~ e 4e...66 REFERENCES CITED ............................................... 71 APPENDIX A - Triangulation Points for Site Datum Stakes ........ 73

  13. Biopharmaceutics data management system for anonymised data sharing and curation: First application with orbito IMI project.

    PubMed

    Lacy-Jones, Kristin; Hayward, Philip; Andrews, Steve; Gledhill, Ian; McAllister, Mark; Abrahamsson, Bertil; Rostami-Hodjegan, Amin; Pepin, Xavier

    2017-03-01

    The OrBiTo IMI project was designed to improve the understanding and modelling of how drugs are absorbed. To achieve this 13 pharmaceutical companies agreed to share biopharmaceutics drug properties and performance data, as long as they were able to hide certain aspects of their dataset if required. This data was then used in simulations to test how three in silico Physiological Based Pharmacokinetic (PBPK) tools performed. A unique database system was designed and implemented to store the drug data. The database system was unique, in that it had the ability to make different sections of a dataset visible or hidden depending on the stage of the project. Users were also given the option to hide identifying API attributes, to help prevent identification of project members from previously published data. This was achieved by applying blinding strategies to data parameters and the adoption of a unique numbering system. An anonymous communication tool was proposed to exchange comments about data, which enabled its curation and evolution. This paper describes the strategy adopted for numbering and blinding of the data, the tools developed to gather and search data as well as the tools used for communicating around the data with the aim of publicising the approach for other pre-competitive research between organisations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Getting Digital Assets from Public-Private Partnership Research Projects through "The Valley of Death," and Making Them Sustainable.

    PubMed

    Aartsen, Wendy; Peeters, Paul; Wagers, Scott; Williams-Jones, Bryn

    2018-01-01

    Projects in public-private partnerships, such as the Innovative Medicines Initiative (IMI), produce data services and platforms (digital assets) to help support the use of medical research data and IT tools. Maintaining these assets beyond the funding period of a project can be a challenge. The reason for that is the need to develop a business model that integrates the perspectives of all different stakeholders involved in the project, and these digital assets might not necessarily be addressing a problem for which there is an addressable market of paying customers. In this manuscript, we review four IMI projects and the digital assets they produced as a means of illustrating the challenges in making digital assets sustainable and the lessons learned. To progress digital assets beyond proof-of-concept into widely adopted tools, there is a need for continuation of multi-stakeholder support tailored to these assets. This would be best done by implementing a structure similar to the accelerators that are in place to help transform startup businesses into growing and thriving businesses. The aim of this article is to highlight the risk of digital asset loss and to provoke discussion on the concept of developing an "accelerator" for digital assets from public-private partnership research projects to increase the chance that digital assets will be sustained and continue to add value long after a project has ended.

  15. Synthesis, spectroscopic characterizations, crystal structures and DFT studies of nalidixic acid carbonyl hydrazones derivatives

    NASA Astrophysics Data System (ADS)

    Bergamini, F. R. G.; Ribeiro, M. A.; Lancellotti, M.; Machado, D.; Miranda, P. C. M. L.; Cuin, A.; Formiga, A. L. B.; Corbi, P. P.

    2016-09-01

    This article describes the synthesis and characterization of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide (hzd) and six carbonyl hydrazones derivatives of the nalidixic with 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene(h4py) and (2-hydroxyphenyl)methylidene (hsali). The carbonyl hydrazones were characterized by elemental and ESI-QTOF-MS analyses, IR and detailed NMR spectroscopic measurements. The 2D NMR experiments allowed the unambiguous assignment of the hydrogen, carbon and nitrogen atoms, which have not been reported for nalidixic acid carbonyl hydrazone derivatives so far. Crystal structures of hzd and the new carbonyl hydrazones h2imi, hpyrr and h3py were determined by X-ray diffraction studies. Although the synthesis of hzd was reported decades ago, the hzd crystal structure have not been reported yet. Geometric optimizations of all the characterized structures were performed with the aid of DFT studies. Despite the fact that the hydrazones with 2-pyridine carboxylic acid (h2py) and salicyl aldehyde (hsali) were already reported by literature, a detailed spectroscopic study followed by DFT studies are also reported for such compounds in this manuscript. Antimicrobial studies of the compounds are also presented.

  16. Evaluation of the Antioxidant Activities and Tyrosinase Inhibitory Property from Mycelium Culture Extracts

    PubMed Central

    Park, Ki Moon; Kwon, Kyung Min; Lee, Seung Ho

    2015-01-01

    Since mushrooms have many bioactive components, they have been used as components in folk medicine. Because mycelium has an advantage when it comes to large-scale production, this study aimed to evaluate the antioxidant properties and anti-tyrosinase activity from 55 mycelia in culture media. Relatively high 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity was detected from the ethanol extract of culture media including mycelium (EECiM) of Morchella esculenta var. esculenta (MEVE), Auricularia polytricha (APO), Tremella aurantia (TAU), Volvariella bombycina (VBO), and Oudemansiella sp. (Osp), which also showed strong reducing power and inhibitory activity in relation to the thiobarbituric acid (TBA) value. On the other hand, relatively high tyrosinase inhibitory activity was detected in Inonotus mikadoi (IMI), Coriolus versicolor (CVE), Volvariella volvacea (VVO), Panellus serotinus (PSE), Auricularia auricula (AAU), and Fomitopsis sp. (Fsp). Interestingly, the APO EECiM exhibited the highest DPPH radical scavenging rate (77.5 ± 4.3%) and reducing power (1.18 ± 0.041), while the highest inhibitory power of the TBA value and antityrosinase activity were detected in that of TAU (64.5 ± 4.1%) and IMI (46.0 ± 7.5%), respectively. Overall, our study suggested potential candidates for EECiMs that exhibited powerful antioxidant and tyrosinase inhibitory properties and might be used as natural antioxidant tyrosinase inhibitor. PMID:26345142

  17. Optimization of laccase production by Pleurotus ostreatus IMI 395545 using the Taguchi DOE methodology.

    PubMed

    Periasamy, Rathinasamy; Palvannan, Thayumanavan

    2010-12-01

    Production of laccase using a submerged culture of Pleurotus orstreatus IMI 395545 was optimized by the Taguchi orthogonal array (OA) design of experiments (DOE) methodology. This approach facilitates the study of the interactions of a large number of variables spanned by factors and their settings, with a small number of experiments, leading to considerable savings in time and cost for process optimization. This methodology optimizes the number of impact factors and enables to calculate their interaction in the production of industrial enzymes. Eight factors, viz. glucose, yeast extract, malt extract, inoculum, mineral solution, inducer (1 mM CuSO₄) and amino acid (l-asparagine) at three levels and pH at two levels, with an OA layout of L18 (2¹ × 3⁷) were selected for the proposed experimental design. The laccase yield obtained from the 18 sets of fermentation experiments performed with the selected factors and levels was further processed with Qualitek-4 software. The optimized conditions shared an enhanced laccase expression of 86.8% (from 485.0 to 906.3 U). The combination of factors was further validated for laccase production and reactive blue 221 decolorization. The results revealed an enhanced laccase yield of 32.6% and dye decolorization up to 84.6%. This methodology allows the complete evaluation of main and interaction factors. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  18. Predicting story goodness performance from cognitive measures following traumatic brain injury.

    PubMed

    Lê, Karen; Coelho, Carl; Mozeiko, Jennifer; Krueger, Frank; Grafman, Jordan

    2012-05-01

    This study examined the prediction of performance on measures of the Story Goodness Index (SGI; Lê, Coelho, Mozeiko, & Grafman, 2011) from executive function (EF) and memory measures following traumatic brain injury (TBI). It was hypothesized that EF and memory measures would significantly predict SGI outcomes. One hundred sixty-seven individuals with TBI participated in the study. Story retellings were analyzed using the SGI protocol. Three cognitive measures--Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001) Sorting Test, Wechsler Memory Scale--Third Edition (WMS-III; Wechsler, 1997) Working Memory Primary Index (WMI), and WMS-III Immediate Memory Primary Index (IMI)--were entered into a multiple linear regression model for each discourse measure. Two sets of regression analyses were performed, the first with the Sorting Test as the first predictor and the second with it as the last. The first set of regression analyses identified the Sorting Test and IMI as the only significant predictors of performance on measures of the SGI. The second set identified all measures as significant predictors when evaluating each step of the regression function. The cognitive variables predicted performance on the SGI measures, although there were differences in the amount of explained variance. The results (a) suggest that storytelling ability draws on a number of underlying skills and (b) underscore the importance of using discrete cognitive tasks rather than broad cognitive indices to investigate the cognitive substrates of discourse.

  19. Tumor-infiltrating Tim-3+ T cells proliferate avidly except when PD-1 is co-expressed: Evidence for intracellular cross talk

    PubMed Central

    Li, Jing; Shayan, Gulidanna; Avery, Lyndsay; Jie, Hyun-Bae; Gildener-Leapman, Neil; Schmitt, Nicole; Lu, Bin Feng; Kane, Lawrence P.; Ferris, Robert L.

    2016-01-01

    ABSTRACT Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes (TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3 is proposed to mark more extensively exhausted cells, although the mechanisms underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have identified a large subset of non-responder patients, likely due to expression of alternative checkpoint molecules like Tim-3. We investigated the phenotypic and functional characteristics of T cells with differential expression of PD-1 (high/low) and Tim-3 (positive/negative), using TIL directly isolated from head and neck squamous cell carcinomas (HNSCC). Unexpectedly, we found that expression of Tim-3 alone does not necessarily mark TIL as dysfunctional/exhausted. In Tim-3-TIL, PD-1 levels correlate with T cell dysfunction, with a PD-1low/intermed phenotype identifying recently activated and still functional cells, whereas PD-1hiTim-3− T cells are actually exhausted. Nonetheless, PD-1intermed cells are still potently suppressed by PD-L1. PD-1 expression was associated with reduced phosphorylation of ribosomal protein S6 (pS6), whereas Tim-3 expression was associated with increased pS6. Using a novel mouse model for inducible Tim-3 expression, we confirmed that expression of Tim-3 does not necessarily render T cells refractory to further activation. These results suggest the existence of PD-1 and Tim-3 crosstalk in regulating antitumor T cell responses, with important implications for anti-PD-1 immunotherapy. PMID:27853635

  20. Radio-induced inherited sterility in Heliothis zea (Boddie)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carpenter, J.E.

    1985-01-01

    Heliothis zea (Boddie) (Lepidoptera: Noctuidae) males and females were irradiated with substerilizing doses of radiation. These moths were inbred and outcrossed and observed for their ability to reproduce. The inherited deleterious effects resulting from the irradiated P/sub 1/ males were recorded for several generations. Larvae from both irradiated (10 krad) and normal parents were compared for their ability to survive under field conditions on whole-stage sweet corn and these results were compared with those from a laboratory study using meridic diet. Irradiated males and females and F/sub 1/ males from an irradiated (10 krad) male x normal female cross weremore » released in the field and in field cages and observed for their ability to search/attract and secure a mate. Females that had mated with normal and irradiated (10 krad) males were studied to determine the effect of different mating histories on the subsequent mating propensity of the females. A 10-krad dose of radiation induced deleterious effects which were inherited through the F/sub 2/ generation. These radiation-induced deleterious effects were similar to those reported in other species of Lepidoptera. The relationship between the survival of normal larvae and larvae from irradiated parents was similar under laboratory and field rearing conditions. Females mated to normal males and males irradiated with 10 krad had the same mating propensity and experienced the same intermating interval. These effects of substerilizing doses of radiation and inherited sterility on the reproductive ability and behavior of H. zea suggest that a great potential exists for population suppression.« less

  1. Genetic and agronomic assessment of cob traits in corn under low and normal nitrogen management conditions.

    PubMed

    Jansen, Constantin; Zhang, Yongzhong; Liu, Hongjun; Gonzalez-Portilla, Pedro J; Lauter, Nick; Kumar, Bharath; Trucillo-Silva, Ignacio; Martin, Juan Pablo San; Lee, Michael; Simcox, Kevin; Schussler, Jeff; Dhugga, Kanwarpal; Lübberstedt, Thomas

    2015-07-01

    Exploring and understanding the genetic basis of cob biomass in relation to grain yield under varying nitrogen management regimes will help breeders to develop dual-purpose maize. With rising energy demands and costs for fossil fuels, alternative energy from renewable sources such as maize cobs will become competitive. Maize cobs have beneficial characteristics for utilization as feedstock including compact tissue, high cellulose content, and low ash and nitrogen content. Nitrogen is quantitatively the most important nutrient for plant growth. However, the influence of nitrogen fertilization on maize cob production is unclear. In this study, quantitative trait loci (QTL) have been analyzed for cob morphological traits such as cob weight, volume, length, diameter and cob tissue density, and grain yield under normal and low nitrogen regimes. 213 doubled-haploid lines of the intermated B73 × Mo17 (IBM) Syn10 population have been resequenced for 8575 bins, based on SNP markers. A total of 138 QTL were found for six traits across six trials using composite interval mapping with ten cofactors and empirical comparison-wise thresholds (P = 0.001). Despite moderate to high repeatabilities across trials, few QTL were consistent across trials and overall levels of explained phenotypic variance were lower than expected some of the cob trait × trial combinations (R (2) = 7.3-43.1 %). Variation for cob traits was less affected by nitrogen conditions than by grain yield. Thus, the economics of cob usage under low nitrogen regimes is promising.

  2. Span of Control and Initiative: Is More, Less?

    DTIC Science & Technology

    1990-12-18

    Theory., (Homewood: Richard D. Irwin, 1976), pp. 36, 45; Andrew D. Szilagyi and Marc J. Wallace , Organizational Behavior al .Permane 3d ed. (Santa Monica...325; Koontz, p. 242; Koontz, ReagIMI pp. 219, 221; Litterer, p. 573; Moore, p. 1-44; Porter, p. 252; Szilagyi , p. 453. 40. Albers, pp. 155-156; Allen...Litterer, p. 562; Szilagyi , p. 453. 46. Ibid. 47. William S. Lind, "The Changing Face of War: Into the Fourth Generation," p. 2. 48. Schneider, p. 37. 49

  3. Installation Restoration Program Stage 2-1 Remedial Investigation. Beale Air Force Base, Marysville, California. Volume 3. Appendix B - K

    DTIC Science & Technology

    1991-03-29

    I0IYOiHPI1 ISenu n!W .46 ,.II I J LIo Yg I 0 lf I IJliGn I r IM,I I.E_ I IVAna di mjdIIi ~ LaIIII j~inc zo- 20 III IT _______ di ~ ’n F-256 / ____CHZN...VJ is the lijit of detecticq fcr ’thit cvicmud. ba~ ern 1flutic-1. irdicates in estisated trice a lh ANAL Y ST :________________ OrRF.OED BY

  4. A Structural Weight Estimation Program (SWEEP) for Aircraft. Volume 2 - Program Integration and Data Management Module. Part 1: Program Integration

    DTIC Science & Technology

    1974-06-01

    MWl.OMSI«S>.0*tHlT«l,«lll«i OIIOSIOH OWIItl.OVHfMl ,D«VIMl .OMIIWOI . OVNI IMI .OVUIl IOMl oiicisiiM toiiMi, anii in lOUIvaOMX IOIII.TCinilll...0VII7lll.lD«VIII.DV»«lll. I IIMIII.DV«>IIII.IO«NI|1.0Vlt7IM.IOWTlll.DVIII2IM NMWUMK llonil.DVOIMIll. IVHI11 . OVNI tl II c OU ««MlLDVlll.tUOIfl

  5. Semiempirical Dissipation Source Functions for Ocean Waves. Part 1: Definition, Calibration, and Validation

    DTIC Science & Technology

    2010-09-01

    REPORT DATE (DD-MM- YYYY) 02-03-2011 2. REPORT TYPE Journal Article 3 . DATES COVERED (From - To) 4. TITLE AND SUBTITLE Semiempirical Dissipation...Spectral wave modeling has been performed for the "£_ <• , r. , r , r M> l . en • .u u i .• rll ;imi nl .K. •ihr (l’ last...wind output). The nonlinear scattering term Sn\\ repre- sents all processes that lead to an exchange of wave en - ergy between the different spectral

  6. Easy Impossibility Proofs for Distributed Concensus Problems.

    DTIC Science & Technology

    1985-07-01

    device F such that in any system t which u rums F, dhe behavor of each outedge (4.9) b Er In this case, we write FA(E.Ed for F. This axiom expmees a pom...node ad edO bebaiorn SylLSimilarly. Iflbasysm dien A is dwsystcmobtained byscwafteswaydock In 1y h. Intuitively, a scled dock or behavor is in the...Agency Branch Office, Pasadena ATTN: Program MonagemeIIIIIIntIMIS 1030 gast Green Street 1400 Wilson Boulevard Pasadena, CA 91106 Arlington, VA 22209 (1

  7. Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

    PubMed

    Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

    2018-03-01

    Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

  8. Comparative evaluation of a new commercial media, the CHROMAgar™ mSuperCARBA™, for the detection of carbapenemase-producing Enterobacteriaceae.

    PubMed

    Amar, Ma'ayan; Shalom, Ohad; Adler, Amos

    2017-05-01

    A new chromogenic-based medium (mSuperCARBA™) was tested for screening carbapenemase-producing Enterobacteriaceae (CPE). mSuperCARBA™ was more sensitive (83%) in detecting CPE isolates (n=69, including KPC, NDM, OXA-48, VIM, and IMI) compared with CHROMAgar™-KPC (65%) and MacConkey agar with Imipenem (69%) with comparable specificity for non carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (n=29). Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Development of Barrier Materials for Flexible Aircraft Engine Containers

    DTIC Science & Technology

    1977-05-01

    niif ^»imi,ii ^WMM 1 i...ÄWMHWÜippHI ■" ’ " ■ " -" I—i»*f^^ MM^Mimai ^m t Figure 7. Figure 8. Figure 9 . Figure 10. Figure 11. Figure 12. Figure 13. Figure 14. Figure...Evaluation Program 8 Barrier Material Test Data 9 iv % •■■~v’ ■ ■Ä’ ■" mam --"■- ——,«. ms"-- «r MlMiafhf^ - ■"’ ^-g^aaa--^-^^"’^-’

  10. The influence of feeding and fasting on plasma metabolites in the dogfish shark (Squalus acanthias).

    PubMed

    Wood, Chris M; Walsh, Patrick J; Kajimura, Makiko; McClelland, Grant B; Chew, Shit F

    2010-04-01

    Dogfish sharks are opportunistic predators, eating large meals at irregular intervals. Here we present a synthesis of data from several previous studies on responses in plasma metabolites after natural feeding and during prolonged fasting (up to 56days), together with new data on changes in plasma concentrations of amino acids and non-esterified fatty acids. Post-prandial and long-term fasting responses were compared to control sharks fasted for 7days, a typical inter-meal interval. A feeding frenzy was created in which dogfish were allowed to feed naturally on dead teleosts at two consumed ration levels, 2.6% and 5.5% of body weight. Most responses were more pronounced at the higher ration level. These included increases in urea and TMAO concentrations at 20h, followed by stability through to 56days of fasting. Ammonia levels were low and exhibited little short-term response to feeding, but declined to very low values during the extended fast. Glucose and beta-hydroxybutyrate both fell after feeding, the latter to a greater and more prolonged extent (up to 60h), whereas acetoacetate did not change. During prolonged fasting, glucose concentrations were well regulated, but beta-hydroxybutyrate increased to 2-3-fold control levels. Total plasma amino acid concentrations increased in a biphasic fashion, with peaks at 6-20h, and 48-60h after the meal, followed by homeostasis during the extended fast. Essential and non-essential amino acids generally followed this same pattern, though some exhibited different trends after feeding: taurine, beta-alanine, and glycine (decreases or stability), alanine and glutamine (modest prolonged increases), and threonine, serine, asparagine, and valine (much larger short-term increases). Plasma non-esterified fatty acid concentrations declined markedly through 48h after the 2.6% meal. These data are interpreted in light of companion studies showing elevations in aerobic metabolic rate, urea production, rectal gland function, metabolic base excretion, and activation of ornithine-urea cycle and aerobic enzymes after the meal, and muscle N-depletion but maintenance of osmolality and urea production during long-term fasting.

  11. Dynamics and structure of the Alpine Fold Belt

    NASA Technical Reports Server (NTRS)

    Kahle, H. G.

    1985-01-01

    The structure and present-day dynamics of the Alps interms of geodesy and gravimetry are discusssed. A strong correlation of precise leveling and isostatic gravity along the central Alpine chain, especially in Canton Graubunden, East Switzerland are shown. It is assumed that the uplift is partly controlled by isostatic rebound effects. Field observations indicate that these phenomena are still active in the Alps. The study of the uplift processes by applying a number of geodetic and gravimetric measuring techniques, such as the determination of nonperiodic secular variations of gravity, of the deflections of the vertical and tilt changes monitored by hydrostatic leveling is proposed.

  12. Flight Operations in the Sells Airspace Overlying the Tohono O’Odham Indian Reservation and Organ Pipe Cactus Nat’l Monument. Volume 2

    DTIC Science & Technology

    1988-08-01

    by crash- associated fires. I -2 An Epual Opportunity Agency b. all off-road tracks created by vehicles driven to the site to retrieve the wreakage...require responses: 1. The DEIS established that in 1977, 10,394 supersonic sorties capable of creating sonic booms were flown in the Sells Airspace, DEIS...report discuss the effect of a typical case of a F-16 aircraft flying at interme- diate power and z00 feet AGL creating a noise of 103dB. RDEI3 §4.3.2.1

  13. A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function

    PubMed Central

    Liu, Yaobin; Huang, Xiangao; He, Xian; Zhou, Yanqing; Jiang, Xiaogang; Chen-Kiang, Selina; Jaffrey, Samie R.; Xu, Guoqiang

    2015-01-01

    The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomide and pomalidomide are highly effective in treating clinical indications. Thalidomide binds to cereblon (CRBN), a substrate receptor of the cullin-4 really interesting new gene (RING) E3 ligase complex. Here, we examine the effect of thalidomide and its analogs on CRBN ubiquitination and its functions in human cell lines. We find that the ubiquitin modification of CRBN includes K48-linked polyubiquitin chains and that thalidomide blocks the formation of CRBN-ubiquitin conjugates. Furthermore, we show that ubiquitinated CRBN is targeted for proteasomal degradation. Treatment of human myeloma cell lines such as MM1.S, OPM2, and U266 with thalidomide (100 μM) and its structural analog lenalidomide (10 μM) results in stabilization of CRBN and elevation of CRBN protein levels. This in turn leads to the reduced level of CRBN target proteins and enhances the sensitivity of human multiple myeloma cells to IMiDs. Our results reveal a novel mechanism by which thalidomide and its analogs modulate the CRBN function in cells. Through inhibition of CRBN ubiquitination, thalidomide and its analogs allow CRBN to accumulate, leading to the increased cullin-4 RING E3 ligase-mediated degradation of target proteins.—Liu, Y., Huang, X., He, X., Zhou, Y., Jiang, X., Chen-Kiang, S., Jaffrey, S. R., Xu, G. A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function. PMID:26231201

  14. [Hospital San Juan de Dios: actor and victim of the public policies in Colombia].

    PubMed

    Pinilla, María Y; Abadía, César E

    2017-01-01

    In this article, we narrate and analyze the historical configuration that a group of female workers and a collective of social organizations made about the Hospital San Juan de Dios (HSJD) and Instituto Materno Infantil (IMI) in Bogotá, Colombia, within the neoliberal crisis in health. Our ethnographic research intersects the Latinamerican traditions of collaborative ethnography and historic anthropology. The research was conducted in two sites. In the first one, from 2005 until 2015, we had informal conversations and conducted workshops and semi-structured interviews with IMI workers. The second site corresponds to our participation in the deliberations of the Mesa Jurídica por el San Juan de Dios (2008-2009), which aimed to elevate a class action to defend the hospitals. We found that workers and social organizations made use of the colonial origin of the hospitals and their institutionalization as center of welfare policies in the country as a way to highlight their patrimonial, historical, educational and social importance. This historical construction critiques efforts that negate or transform the public character of the hospitals and helped them carry on different actions to denounce the neoliberal health care reform as the cause of the hospitals most important crisis and closing. The different actors denounce the change in the hospitals-state relationship, which transited from being central for the development of social policies to reflecting a symbolic and material elimination of the hospitals. Such transition benefits the market interests established by the neoliberal model.

  15. Motivation Measures in Sport: A Critical Review and Bibliometric Analysis.

    PubMed

    Clancy, Rachel B; Herring, Matthew P; Campbell, Mark J

    2017-01-01

    Motivation is widely-researched, in both sport psychology and other fields. As rigorous measurement is essential to understanding this latent construct, a critical appraisal of measurement instruments is needed. Thus, the purpose of this review was to evaluate the six most highly cited motivation measures in sport. Peer-reviewed articles published prior to August 2016 were searched to identify the six most highly cited motivation questionnaires in sport: Sport Motivation Scale (SMS), Intrinsic Motivation Inventory (IMI), Situational Motivational Scale (SIMS), Perceptions of Success Questionnaire (POSQ), Behavioural Regulation in Sport Questionnaire (BRSQ), and Task and Ego Orientation in Sport Questionnaire (TEOSQ). The questionnaires were then evaluated and discussed in four sections: Development, Reliability, Correlates, and Summary. Bibliometric data were also calculated (average weighted impact factor) and assessed (e.g., citations per year) to evaluate the impact of the use of each questionnaire. Despite some variance in their psychometric properties, conceptualization, structure, and utility, the six questionnaires are psychometrically strong instruments for quantifying motivation that are widely supported in the literature. Bibliometric analyses suggested that the IMI ranks first and the SMS ranks sixth according to the average weighted impact factors of their original publications. Consideration of each questionnaire's psychometric strengths/limitations, and conceptualization of motivation in the context of specific research questions should guide researchers in selecting the most appropriate instrument to measure motivation in sport. The average weighted impact factor of each questionnaire is a useful value to consider as well. With these points in mind, recommendations are provided.

  16. Getting Digital Assets from Public–Private Partnership Research Projects through “The Valley of Death,” and Making Them Sustainable

    PubMed Central

    Aartsen, Wendy; Peeters, Paul; Wagers, Scott; Williams-Jones, Bryn

    2018-01-01

    Projects in public–private partnerships, such as the Innovative Medicines Initiative (IMI), produce data services and platforms (digital assets) to help support the use of medical research data and IT tools. Maintaining these assets beyond the funding period of a project can be a challenge. The reason for that is the need to develop a business model that integrates the perspectives of all different stakeholders involved in the project, and these digital assets might not necessarily be addressing a problem for which there is an addressable market of paying customers. In this manuscript, we review four IMI projects and the digital assets they produced as a means of illustrating the challenges in making digital assets sustainable and the lessons learned. To progress digital assets beyond proof-of-concept into widely adopted tools, there is a need for continuation of multi-stakeholder support tailored to these assets. This would be best done by implementing a structure similar to the accelerators that are in place to help transform startup businesses into growing and thriving businesses. The aim of this article is to highlight the risk of digital asset loss and to provoke discussion on the concept of developing an “accelerator” for digital assets from public–private partnership research projects to increase the chance that digital assets will be sustained and continue to add value long after a project has ended. PMID:29594123

  17. Motivation Measures in Sport: A Critical Review and Bibliometric Analysis

    PubMed Central

    Clancy, Rachel B.; Herring, Matthew P.; Campbell, Mark J.

    2017-01-01

    Motivation is widely-researched, in both sport psychology and other fields. As rigorous measurement is essential to understanding this latent construct, a critical appraisal of measurement instruments is needed. Thus, the purpose of this review was to evaluate the six most highly cited motivation measures in sport. Peer-reviewed articles published prior to August 2016 were searched to identify the six most highly cited motivation questionnaires in sport: Sport Motivation Scale (SMS), Intrinsic Motivation Inventory (IMI), Situational Motivational Scale (SIMS), Perceptions of Success Questionnaire (POSQ), Behavioural Regulation in Sport Questionnaire (BRSQ), and Task and Ego Orientation in Sport Questionnaire (TEOSQ). The questionnaires were then evaluated and discussed in four sections: Development, Reliability, Correlates, and Summary. Bibliometric data were also calculated (average weighted impact factor) and assessed (e.g., citations per year) to evaluate the impact of the use of each questionnaire. Despite some variance in their psychometric properties, conceptualization, structure, and utility, the six questionnaires are psychometrically strong instruments for quantifying motivation that are widely supported in the literature. Bibliometric analyses suggested that the IMI ranks first and the SMS ranks sixth according to the average weighted impact factors of their original publications. Consideration of each questionnaire's psychometric strengths/limitations, and conceptualization of motivation in the context of specific research questions should guide researchers in selecting the most appropriate instrument to measure motivation in sport. The average weighted impact factor of each questionnaire is a useful value to consider as well. With these points in mind, recommendations are provided. PMID:28337165

  18. Measuring motivation in schizophrenia: Is a general state of motivation necessary for task-specific motivation?

    PubMed Central

    Choi, Jimmy; Choi, Kee-Hong; Reddy, Felice; Fiszdon, Joanna M.

    2014-01-01

    Despite the important role of motivation in rehabilitation and functional outcomes in schizophrenia, to date, there has been little emphasis on how motivation is assessed. This is important, since different measures may tap potentially discrete motivational constructs, which in turn may have very different associations to important outcomes. In the current study, we used baseline data from 71 schizophrenia spectrum outpatients enrolled in a rehabilitation program to examine the relationship between task-specific motivation, as measured by the Intrinsic Motivation Inventory (IMI), and a more general state of volition/initiation, as measured by the three item Quality of Life (QLS) motivation index. We also examined the relationship of these motivation measures to demographic, clinical and functional variables relevant to rehabilitation outcomes. The two motivation measures were not correlated, and participants with low general state motivation exhibited a full range of task-specific motivation. Only the QLS motivation index correlated with variables relevant to rehabilitation outcomes. The lack of associations between QLS motivation index and IMI subscales suggests that constructs tapped by these measures may be divergent in schizophrenia, and specifically that task-specific intrinsic motivation is not contingent on a general state of motivation. That is, even in individuals with a general low motivational state (i.e. amotivation), interventions aimed at increasing task-specific motivation may still be effective. Moreover, the pattern of interrelationships between the QLS motivation index and variables relevant to psychosocial rehabilitation supports its use in treatment outcome studies. PMID:24529609

  19. Cadmium induces cadmium-tolerant gene expression in the filamentous fungus Trichoderma harzianum.

    PubMed

    Cacciola, Santa O; Puglisi, Ivana; Faedda, Roberto; Sanzaro, Vincenzo; Pane, Antonella; Lo Piero, Angela R; Evoli, Maria; Petrone, Goffredo

    2015-11-01

    The filamentous fungus Trichoderma harzianum, strain IMI 393899, was able to grow in the presence of the heavy metals cadmium and mercury. The main objective of this research was to study the molecular mechanisms underlying the tolerance of the fungus T. harzianum to cadmium. The suppression subtractive hybridization (SSH) method was used for the characterization of the genes of T. harzianum implicated in cadmium tolerance compared with those expressed in the response to the stress induced by mercury. Finally, the effects of cadmium exposure were also validated by measuring the expression levels of the putative genes coding for a glucose transporter, a plasma membrane ATPase, a Cd(2+)/Zn(2+) transporter protein and a two-component system sensor histidine kinase YcbA, by real-time-PCR. By using the aforementioned SSH strategy, it was possible to identify 108 differentially expressed genes of the strain IMI 393899 of T. harzianum grown in a mineral substrate with the addition of cadmium. The expressed sequence tags identified by SSH technique were encoding different genes that may be involved in different biological processes, including those associated to primary and secondary metabolism, intracellular transport, transcription factors, cell defence, signal transduction, DNA metabolism, cell growth and protein synthesis. Finally, the results show that in the mechanism of tolerance to cadmium a possible signal transduction pathway could activate a Cd(2+)/Zn(2+) transporter protein and/or a plasma membrane ATPase that could be involved in the compartmentalization of cadmium inside the cell.

  20. Cow characteristics and their association with udder health after different dry period lengths.

    PubMed

    van Hoeij, R J; Lam, T J G M; de Koning, D B; Steeneveld, W; Kemp, B; van Knegsel, A T M

    2016-10-01

    Shortening or omitting the dry period (DP) in dairy cows is of interest because of potential beneficial effects on energy balance and metabolic health. Reported effects of a short or omitted dry period on udder health are ambiguous. This study aimed to evaluate the effect of no DP (0d), a short DP (30d), or a conventional DP (60 d) on the occurrence of intramammary infections (IMI) during the precalving period and on somatic cell counts (SCC), elevations of SCC (SCC≥200,000 cells/mL), and clinical mastitis in the subsequent lactation. The study also aimed to analyze which prepartum cow characteristics are associated with udder health after different DP lengths. Holstein-Friesian dairy cows (n=167) were randomly assigned to a DP length (0, 30, or 60 d). Cows with a 0-d DP had a greater occurrence of chronic IMI and a lower occurrence of cured IMI during the precalving period than cows with a 30-d or 60-d DP. Postpartum average SCC for lactation was greater in cows with a 0-d DP than in cows with a 30-d or 60-d DP. The number of cows with at least 1 elevation of SCC, the number of elevations of SCC per affected cow, the number of cows treated for clinical mastitis, and the number of cases of mastitis per affected cow did not differ among DP lengths. Cow characteristics related to postpartum average SCC for lactation were DP length, parity, and the following interactions: DP length with prepartum elevation of SCC, DP length with fat- and protein-corrected milk (FPCM) reduction between 150 and 67d prepartum, DP length with parity and with average SCC for lactation, and last FPCM before the conventional drying-off day with average SCC for lactation. Cows with prepartum parity 1 had a lower occurrence of at least 1 elevation of SCC in subsequent lactation compared with cows with parity >2. Last SCC before the conventional drying-off day was positively associated with occurrence of clinical mastitis in the subsequent lactation. In this study, DP length was not a risk factor for either elevation of SCC or occurrence of clinical mastitis in the subsequent lactation. The identified cow characteristics could be used in a decision support model to optimize DP length for individual cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. Effectiveness and cost-effectiveness of a guided Internet- and mobile-based intervention for the indicated prevention of major depression in patients with chronic back pain-study protocol of the PROD-BP multicenter pragmatic RCT.

    PubMed

    Sander, L; Paganini, S; Lin, J; Schlicker, S; Ebert, D D; Buntrock, C; Baumeister, H

    2017-01-21

    Reducing the disease burden of major depressive disorder (MDD) is of major public health relevance. The prevention of depression is regarded as one possible approach to reach this goal. People with multiple risk factors for MDD such as chronic back pain and subthreshold depressive symptoms may benefit most from preventive measures. The Internet as intervention setting allows for scaling up preventive interventions on a public mental health level. This study is a multicenter pragmatic randomized controlled trial (RCT) of parallel design aiming to investigate the (cost-) effectiveness of an Internet- and mobile-based intervention (IMI) for the prevention of depression in chronic back pain patients (PROD-BP) with subthreshold depressive symptoms. eSano BackCare-DP is a guided, chronic back pain-specific depression prevention intervention based on cognitive behavioral therapy (CBT) principles comprising six weekly plus three optional modules and two booster sessions after completion of the intervention. Trained psychologists provide guidance by sending feedback messages after each module. A total of 406 patients with chronic back pain and without a depressive disorder at baseline will be recruited following orthopedic rehabilitation care and allocated to either intervention or treatment-as-usual (TAU). Primary patient-relevant endpoint of the trial is the time to onset of MDD measured by the telephone-administered Structured Clinical Interview for DSM (SCID) at baseline and 1-year post-randomization. Key secondary outcomes are health-related quality of life, depression severity, pain intensity, pain-related disability, ability to work, intervention satisfaction and adherence as well as side effects of the intervention. Online assessments take place at baseline and 9 weeks as well as 6 and 12 months post-randomization. Cox regression survival analysis will be conducted to estimate hazard ratio at 12-month follow-up. Moreover, an economic analysis will be conducted from a societal and public health perspective. This is the first study examining an IMI for depression prevention in a sample of chronic pain patients. If this implementation of a depression prevention IMI into orthopedic aftercare proves effective, the intervention could be integrated into routine care with minimal costs and extended for use with other chronic diseases. Results will have implications for researchers, health care providers and public health policy makers. The trial is registered at the WHO International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS): DRKS00007960 . Registered 12 August 2015.

  2. Observations of the California Countercurrent.

    DTIC Science & Technology

    1984-06-01

    m S. P. Tucker Approved for public release; distribut ion tin] imi ted. UnCLASS IFIED W S4(CWftIY CLASSIVICATIOkO r 7.1% PAGE "Wh., Owe Ent.,eai...Idtinity by block number) - -R6sults from moored current meters, 150-350 m , Uru describec~for ai region over the continental slope off Cape San Martin...from ,.ored current net e r 15) - 35q m , are z2-CUS.eJ tar a region over th1e continental _sioLp, .2 "a,, .San rrtin, Cali orn ra . .I nLlarv 1979 to

  3. The Role of Leadership in Navy Program Offices. Executive Summary

    DTIC Science & Technology

    1973-05-01

    PROGRAM MANAGEMENT COURSE- SSTUDENT STUDY PROGRAM Fort Beivoir, Virginia, 22060 THE ROLE OF LEADERSHIP IN NAVY PROGRAM OFFICES STUDY REPORT PMC 73-1...jLa I1 • 1. Men at the Top. Osborne kLliott 1 2. "Understanding Leadership ". W. 0. H. Prentice, HBR Sep- Oct 1966 j 3. "A Theory of Human Motivation...Drucker, IMI reprint 9. Technical Management Institute Thifnkpiece, " Leadership " 1 • 0. "The Effective Manager ". Peter Drucker, LMI r~print 11. Sur-ival In

  4. Testing Methods for Integrated Circuit Chips.

    DTIC Science & Technology

    1986-03-27

    DWf <I IAV ~IMi MORY OUT LOGIC~~ IPOGRAM ASYC S’E4i E...* 16o, CO% T ROL CO%TROL 32 Figure 2 . 14 VLSI Tester Block Diagram. registers, memory and test...neral-pIurpos’ processor wi th standard bus- inte-rfaco se-rves as,- th- test control Ii’r and ( 2 ) a c-ustom VLSI test Controller inti-rfacing direc(_t1...Engineering 2 WTWTY ABSTRACT Provision for the functional testing of fabricated VLSI chips frequently involves as much design effort as the orig- _ inal

  5. Application of Advanced Decision-Analytic Technology to Rapid Deployment Joint Task Force Problems

    DTIC Science & Technology

    1981-06-01

    CHANGE 9 DIEGO GARCIA CHANGE 5: MOMPANA/K FROM I. SO FROM 2: AIRFIELD IMIS TO 2 AIRFIELD IMPS+DRI/II TO 6: COMM/NAV AIDS bENEF IT COET BENEFIT COFF 410...meetings: (1) To organize , display, and update the working group’s judgements about the relative costs and benefits of each level of each variable in...benefit to the organization . (3) Assess costs - In the DESIGN software, there is one type of limited resource to be allocated to the variables. This

  6. Proceedings of the NSW Thermal Workshop, Held in Virginia Beach, Virginia on 16-17 September 1991

    DTIC Science & Technology

    1992-09-01

    average of only 1.2 ’C over the 4- and 6-hour trials. HOT/DRY STRESS PHYSIOLOGICAL RESPONSES Heat stroke: we see a rapid rise in core temperature to...protective measurement? And yet, my data will show an average low core temperature for all the "guys." Say these two guys are average or got to 350 C. 125...nations. LARRY W. LAUGHLIN CAPT, MC, USN Commanding Officer Naval Medical Research institute SJUpl’rtfV StIICAICION Oi iMi PACA REPORT DOCUMENTATION

  7. Flame Resistant Foam

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Solimide manufactured by Imi-Tech Corporation, is a lightweight fire resistant material produced under a manufacturing process that allows it to be uniformly foamed. Can be produced in a variety of densities and structural configurations and remains resilient under exposure to temperatures ranging from minus 300 to plus 500 degrees Fahrenheit. Is resistant to open flame and generates virtually no smoke or toxic by-products. Used in aircraft for its superior damping characteristics, lighter weight and fire barrier properties, it's also applicable to ships and surface transportation systems such as transit cars, trains, buses and automobiles.

  8. M-X Environmental Technical Report. Environmental Characteristics of Alternative Designated Deployment Areas, Wilderness and Significant Natural Areas.

    DTIC Science & Technology

    1980-12-22

    National Forest in northeastern Nevada, and Lone Peak in the Uinta and Wasatch National Forest of central Utah. Each of these areas is more than 60 miles...natural landmarks was obtained from a compre- hensive study of the Great Basin (Bostick et al., 1975) and updated with information from DNL and Nevada...Montains~ 0 ALM :Battle Mtns) 35rks 42.000 .4% 53 I-- Iee -A~IMI Ditrc 10- - - 57 Se"lpeSes - - --- se Midle Img ie. Sle on. - --- 122 Gas . Fairvie

  9. Defense Standardization Program Status of Standardization Projects

    DTIC Science & Technology

    1993-09-30

    GS N 7320 0903 A-A-XXX VEGETABLE PEELING MACHINE ELEC GL B4 A 931 934 934 A GL YDI 99 GS N 7320 0904 MIL-D-13053D NOT 1 DOUGH TROUGHS GL H5 932 941...934 G GL YDi 99 GS U 7320 0906 MIL-D-2471D DOUGH DIVIDING MACHINE GL H5 931 941 934 G GL YDV 99 GS U 7320 0907 MIL-B-43386B NOT 1 BIN INGRE MOBILE GL...H5 932 941 934 G GL YDI 99 GS U 7320 0908 MIL-D-2351C DOUGH INTERMED PRF MACHINE GL H5 932 941 934 G GL YDV 99 GS U 7320 0909 MIL-D-2352C DOUGH

  10. Reduced intestinal brain-derived neurotrophic factor increases vagal sensory innervation of the intestine and enhances satiation.

    PubMed

    Biddinger, Jessica E; Fox, Edward A

    2014-07-30

    Brain-derived neurotrophic factor (BDNF) is produced by developing and mature gastrointestinal (GI) tissues that are heavily innervated by autonomic neurons and may therefore control their development or function. To begin investigating this hypothesis, we compared the morphology, distribution, and density of intraganglionic laminar endings (IGLEs), the predominant vagal GI afferent, in mice with reduced intestinal BDNF (INT-BDNF(-/-)) and controls. Contrary to expectations of reduced development, IGLE density and longitudinal axon bundle number in the intestine of INT-BDNF(-/-) mice were increased, but stomach IGLEs were normal. INT-BDNF(-/-) mice also exhibited increased vagal sensory neuron numbers, suggesting that their survival was enhanced. To determine whether increased intestinal IGLE density or other changes to gut innervation in INT-BDNF(-/-) mice altered feeding behavior, meal pattern and microstructural analyses were performed. INT-BDNF(-/-) mice ate meals of much shorter duration than controls, resulting in reduced meal size. Increased suppression of feeding in INT-BDNF(-/-) mice during the late phase of a scheduled meal suggested that increased satiation signaling contributed to reduced meal duration and size. Furthermore, INT-BDNF(-/-) mice demonstrated increases in total daily intermeal interval and satiety ratio, suggesting that satiety signaling was augmented. Compensatory responses maintained normal daily food intake and body weight in INT-BDNF(-/-) mice. These findings suggest a target organ-derived neurotrophin suppresses development of that organ's sensory innervation and sensory neuron survival and demonstrate a role for BDNF produced by peripheral tissues in short-term controls of feeding, likely through its regulation of development or function of gut innervation, possibly including augmented intestinal IGLE innervation. Copyright © 2014 the authors 0270-6474/14/3410379-15$15.00/0.

  11. The influence of dietary patterns on acne vulgaris in Koreans.

    PubMed

    Jung, Jae Yoon; Yoon, Mi Young; Min, Seong Uk; Hong, Jong Soo; Choi, Yu Sung; Suh, Dae Hun

    2010-01-01

    The association between acne and food has been evaluated with inconsistent results. We enrolled 783 patients with acne and 502 control subjects. For the patients with acne, blood tests for insulin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), post prandial 2 hours blood glucose (PP2), and dehydroepiandrosterone sulphate (DHEAS) were performed. The acne patients were divided into an "aggravated by food" group (AF) and a "not aggravated by food" group (NAF). All participants were asked to fill out a questionnaire. The frequency of vegetables (yellow, green leafy, cruciferous) (P = .001) and fish (white flesh and green fish, blue tuna) ((P = .03) intake was significantly higher in the control group than in the acne group. Intake of instant noodles (P = .01), junk food (P = .002), carbonated drinks (P = .005), snacks (P = .001), processed cheeses (P = .04), pork (braised) (P = .02), pork (roast) (P < .001), chicken (fried) (P = .001), chicken (stewed) (P = .001), nuts (P = .002) and seaweed (P = .003) were significantly higher in the acne patients than in the controls. Intake of roast pork (P = .02), fried chicken (P < .02), and nuts (P = .03) was significantly higher in the AF than NAF. In addition, the regularity of inter-meal intervals (P < .001) and breakfast intake (P < .001) were significantly lower in the acne patients. IGF-1 and IGFBP-3 showed sexual differences. This study also showed that a high glycemic load diet, dairy food intake, high fat diet, and iodine in Korean foods appear to play a role in acne exacerbation. In addition, irregular dietary patterns were found to aggravate acne.

  12. Rats free to select between pure protein and a fat-carbohydrate mix ingest high-protein mixed meals during the dark period and protein meals during the light period.

    PubMed

    Makarios-Lahham, Lina; Roseau, Suzanne M; Fromentin, Gilles; Tome, Daniel; Even, Patrick C

    2004-03-01

    Rats that are allowed to select their diets [dietary self- selection (DSS)] often ingest >30% of their daily energy in the form of protein. Such an intake may seem unhealthy, but the consistency of this choice suggests that it is motivated by physiologic drives. To gain a clearer understanding of how protein selection is structured during DSS, we adapted 12 rats to a standard diet (14% Protein) and then allowed them to choose between two diets, i.e., total milk protein (P) and a mix of carbohydrates and lipids (FC). The protein intake during DSS rose above 40%; assuming an intermeal interval of 10 min, 70% of the energy intake occurred with meals that included both P and FC, with the sequence of FC followed by P preferred to the sequence of P followed by FC (70 vs. 30%, P < 0.001). In addition, energy intake during the light period was reduced to only 10% of the daily energy intake [vs. 30% with the control P14 diet or a with a high-protein diet (50%)], and 90% of the intake was in the form of pure protein meals. In complementary studies, we verified that the high protein intake also occurred when rats were offered casein and whey and was not due to the high palatability of the milk protein. We conclude that a specific feeding pattern accompanies high protein intake in rats allowed DSS. The mechanisms underlying this behavior and its potential beneficial/adverse consequences over the long term still must be clarified.

  13. Phoenixin-14 injected intracerebroventricularly but not intraperitoneally stimulates food intake in rats.

    PubMed

    Schalla, Martha; Prinz, Philip; Friedrich, Tiemo; Scharner, Sophie; Kobelt, Peter; Goebel-Stengel, Miriam; Rose, Matthias; Stengel, Andreas

    2017-10-01

    Phoenixin, a recently discovered 20-amino acid peptide was implicated in reproduction. However, the expression in food intake-regulatory nuclei such as the paraventricular nucleus, the arcuate nucleus and the nucleus of the solitary tract suggests an implication of phoenixin in food intake regulation. Therefore, we investigated the effects of phoenixin-14, the shorter form of phoenixin, on food intake following intracerebroventricular (icv) and intraperitoneal (ip) injection in ad libitum fed male Sprague-Dawley rats. Phoenixin-14 injected icv (0.2, 1.7 or 15nmol/rat) during the light phase induced a dose-dependent increase of light phase food intake reaching significance at a minimum dose of 1.7 nmol/rat (+72%, p<0.05 vs. vehicle) used for all further analyses. Assessment of the food intake microstructure showed an icv phoenixin-14-induced increase in meal size (+51%), meal duration (+157%), time spent in meals (+182%) and eating rate (+123%), while inter-meal intervals (-42%) and the satiety ratio (-64%) were decreased compared to vehicle (p<0.05). When injected icv during the dark phase, no modulation of food intake was observed (p>0.05). The light phase icv phoenixin-14-induced increase of water intake did not reach statistical significance compared to vehicle (+136%, p>0.05). The increase of food intake following icv phoenixin-14 was not associated with a significant alteration of grooming behavior (0.4-fold, p=0.377) or locomotion (6-fold, p=0.066) compared to vehicle. When injected ip at higher doses (0.6, 5nmol/kg or 45nmol/kg body weight) during the light phase, phoenixin-14 did not affect food intake (p>0.05). In summary, phoenixin-14 exerts a centrally-mediated orexigenic effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Natural Variation at sympathy for the ligule Controls Penetrance of the Semidominant Liguleless narrow-R Mutation in Zea mays

    PubMed Central

    Buescher, Elizabeth M.; Moon, Jihyun; Runkel, Anne; Hake, Sarah; Dilkes, Brian P.

    2014-01-01

    Leaf architecture determines plant structural integrity, light harvesting, and economic considerations such as plant density. Ligules, junctions at the leaf sheath and blade in grasses, protect stalks from environmental stresses and, in conjunction with auricles, controls leaf angle. Previous studies in mutants have recessive liguleless mutants (lg1 and lg2) and dominant mutations in knotted1-like homeobox genes (Lg3-O, Lg4, and Kn1) involved in ligule development. Recently, a new semidominant liguleless mutant, Liguleless narrow (Lgn-R), has been characterized in maize that affects ligule and auricle development and results in a narrow leaf phenotype. We show that quantitative genetic variation affects penetrance of Lgn-R. To examine the genetic architecture underlying Lgn-R expressivity, crosses between Lgn-R/+ mutants in a B73 background and intermated B73 x Mo17 recombinant inbred lines were evaluated in multiple years and locations. A single main-effect quantitative trait locus (QTL) on chromosome 1 (sympathy for the ligule; sol) was discovered with a Mo17-contributed allele that suppressed Lgn-R mutant phenotypes. This QTL has a genetic-interaction with a locus on chromosome 7 (lucifer; lcf) for which the B73-contributed allele increases the ability of the solMo17 allele to suppress Lgn-R. Neither of the genetic intervals likely to contain sol or lcf overlap with any current liguleless genes nor with previously identified genome-wide association QTL connected to leaf architecture. Analysis of phenotypes across environments further identified a genotype by enviroment interaction determining the strength of the sol x lcf interaction. PMID:25344411

  15. Effects of eating rate on satiety: A role for episodic memory?

    PubMed Central

    Ferriday, Danielle; Bosworth, Matthew L.; Lai, Samantha; Godinot, Nicolas; Martin, Nathalie; Martin, Ashley A.; Rogers, Peter J.; Brunstrom, Jeffrey M.

    2015-01-01

    Eating slowly is associated with a lower body mass index. However, the underlying mechanism is poorly understood. Here, our objective was to determine whether eating a meal at a slow rate improves episodic memory for the meal and promotes satiety. Participants (N = 40) consumed a 400 ml portion of tomato soup at either a fast (1.97 ml/s) or a slow (0.50 ml/s) rate. Appetite ratings were elicited at baseline and at the end of the meal (satiation). Satiety was assessed using; i) an ad libitum biscuit ‘taste test’ (3 h after the meal) and ii) appetite ratings (collected 2 h after the meal and after the ad libitum snack). Finally, to evaluate episodic memory for the meal, participants self-served the volume of soup that they believed they had consumed earlier (portion size memory) and completed a rating of memory ‘vividness’. Participants who consumed the soup slowly reported a greater increase in fullness, both at the end of the meal and during the inter-meal interval. However, we found little effect of eating rate on subsequent ad libitum snack intake. Importantly, after 3 h, participants who ate the soup slowly remembered eating a larger portion. These findings show that eating slowly promotes self-reported satiation and satiety. For the first time, they also suggest that eating rate influences portion size memory. However, eating slowly did not affect ratings of memory vividness and we found little evidence for a relationship between episodic memory and satiety. Therefore, we are unable to conclude that episodic memory mediates effects of eating rate on satiety. PMID:26143189

  16. Heating and eating: brown adipose tissue thermogenesis precedes food ingestion as part of the ultradian basic rest-activity cycle in rats.

    PubMed

    Blessing, William; Mohammed, Mazher; Ootsuka, Youichirou

    2012-02-28

    Laboratory rats, throughout the 24 hour day, alternate between behaviorally active and non active episodes that Kleitman called the basic rest-activity cycle (BRAC). We previously demonstrated that brown adipose tissue (BAT), body and brain temperatures and arterial pressure and heart rate increase in an integrated manner during behaviorally active phases. Studies show that eating is preceded by increases in body and brain temperature, but whether eating is integrated into the BRAC has not been investigated. In the present study of chronically instrumented, unrestrained Sprague-Dawley rats, peaks in BAT temperature occurred every 96 ± 7 and 162 ± 16 min (mean ± SE, n=14 rats) in dark and light periods respectively, with no apparent underlying regularity. With food available ad libitum, eating was integrated into the BRAC in a temporally precise manner. Eating occurred only after an increase in BAT temperature, commencing 15 ± 1 min (mean ± SE) after the onset of an increase, with no difference between dark and light phases. There were either no or weak preprandial and postprandial relations between intermeal interval and amount eaten during a given meal. Remarkably, with no food available the rat still disturbed the empty food container 16 ± 1 min (p>0.05 versus ad libitum food) after the onset of increases in BAT temperature, and not at other times. Rather than being triggered by changes in levels of body fuels or other meal-associated factors, in sedentary laboratory rats with ad libitum access to food eating commences as part of the ultradian BRAC, a manifestation of intrinsic brain activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Differences in Postprandial Lipid Response to Breast- or Formula-feeding in 8-Week-Old Infants.

    PubMed

    Teller, Inga C; Schoen, Stefanie; van de Heijning, Bert; van der Beek, Eline M; Sauer, Pieter J J

    2017-04-01

    Lipids play important roles in infant growth and development. In this exploratory observational single-center study, we investigated postmeal responses of infants to dietary lipids and differences between breast-feeding (BF) and formula-feeding (FF). Two capillary blood samples were collected from each subject, before and randomly assigned at either 30, 60, 90, 120, 180, or 240 minutes after their respective feeding, followed by measurement of lipid-related plasma parameter concentrations using enzyme-linked immunosorbent assay-based or combined enzymatic and colorimetric methods. The intermeal interval before testing was shorter in the BF (182.91 ± 22.85 minutes, n = 33) versus FF group (214.1 ± 30.76 minutes, n = 34); BF subjects fed 5 minutes longer (BF 20.27 ± 7.7 minutes; FF 14.82 ± 3.57 minutes). Composite postmeal concentration profiles were generated from 59 plasma sample pairs with sufficient volume (BF = 30): triglyceride (TG) baselines were not different. A TG difference was indicated for BF over FF subjects at 30 minutes, for FF over BF subjects at 60 minutes when corrected for baseline. TG responses in both groups appeared and seemed to clear much faster than those reported for adults. The TG:apolipoprotein B48 (ApoB48) ratio suggests that chylomicrons in BF subjects may carry a higher fat load (P < 0.05), compensated by a higher chylomicron number in FF subjects (P < 0.05). Cholesterol in BF subjects was higher and showed an increase after feeding when corrected for baseline. Our results indicate that lipids from either BF or FF may be handled differently in young healthy infants.

  18. Infant regulation of intake: the effect of free glutamate content in infant formulas1234

    PubMed Central

    Ventura, Alison K; Beauchamp, Gary K; Mennella, Julie A

    2012-01-01

    Background: We recently discovered that infants randomly assigned to a formula high in free amino acids (extensive protein hydrolysate formula; ePHF) during infancy consumed less formula to satiation and gained less weight than did infants fed an isocaloric formula low in free amino acids (cow milk formula; CMF). Objective: Because ePHF and CMF differ markedly in concentrations of free glutamate, we tested the hypothesis that the higher glutamate concentrations in ePHF promote satiation and satiety. Design: In this counterbalanced, within-subject study, infants <4 mo of age (n = 30) visited our laboratory for 3 sets of 2 consecutive infant-led formula meals over 3 test days. Infants were fed 1 of 3 isocaloric formulas during each first meal: CMF, ePHF, or CMF with added free glutamate to approximate concentrations in ePHF (CMF+glu). When infants signaled hunger again, they were fed a second meal of CMF. From these data, we calculated satiety ratios for each of the 3 formulas by dividing the intermeal interval by the amount of formula consumed during that particular first meal. Results: Infants consumed significantly less CMF+glu (P < 0.02) and ePHF (P < 0.04) than CMF during the first meals. They also showed greater levels of satiety after consuming CMF+glu or ePHF: satiety ratios for CMF+glu (P < 0.03) and ePHF (P < 0.05) were significantly higher than for CMF. Conclusion: These findings suggest a role of free glutamate in infant intake regulation and call into question the claim that formula feeding impairs infants’ abilities to self regulate energy intake. This trial was registered at clinicaltrials.gov as NCT00957892. PMID:22357724

  19. Effects of eating rate on satiety: A role for episodic memory?

    PubMed

    Ferriday, Danielle; Bosworth, Matthew L; Lai, Samantha; Godinot, Nicolas; Martin, Nathalie; Martin, Ashley A; Rogers, Peter J; Brunstrom, Jeffrey M

    2015-12-01

    Eating slowly is associated with a lower body mass index. However, the underlying mechanism is poorly understood. Here, our objective was to determine whether eating a meal at a slow rate improves episodic memory for the meal and promotes satiety. Participants (N=40) consumed a 400ml portion of tomato soup at either a fast (1.97ml/s) or a slow (0.50ml/s) rate. Appetite ratings were elicited at baseline and at the end of the meal (satiation). Satiety was assessed using; i) an ad libitum biscuit 'taste test' (3h after the meal) and ii) appetite ratings (collected 2h after the meal and after the ad libitum snack). Finally, to evaluate episodic memory for the meal, participants self-served the volume of soup that they believed they had consumed earlier (portion size memory) and completed a rating of memory 'vividness'. Participants who consumed the soup slowly reported a greater increase in fullness, both at the end of the meal and during the inter-meal interval. However, we found little effect of eating rate on subsequent ad libitum snack intake. Importantly, after 3h, participants who ate the soup slowly remembered eating a larger portion. These findings show that eating slowly promotes self-reported satiation and satiety. For the first time, they also suggest that eating rate influences portion size memory. However, eating slowly did not affect ratings of memory vividness and we found little evidence for a relationship between episodic memory and satiety. Therefore, we are unable to conclude that episodic memory mediates effects of eating rate on satiety. Copyright © 2015. Published by Elsevier Inc.

  20. Gene flow from weedy red rice (Oryza sativa L.) to cultivated rice and fitness of hybrids.

    PubMed

    Shivrain, Vinod K; Burgos, Nilda R; Gealy, David R; Sales, Marites A; Smith, Kenneth L

    2009-10-01

    Gene transfer from weeds to crops could produce weedy individuals that might impact upon the evolutionary dynamics of weedy populations, the persistence of escaped genes in agroecosystems and approaches to weed management and containment of transgenic crops. The present aim was to quantify the gene flowrate from weedy red rice to cultivated rice, and evaluate the morphology, phenology and fecundity of resulting hybrids. Field experiments were conducted at Stuttgart and Rohwer, Arkansas, USA. Twelve red rice accessions and an imazethapyr-resistant rice (Imi-R; Clearfield) were used. Hybrids between Imi-R rice x red rice were 138-150 cm tall and flowered 1-5 days later than the rice parent, regardless of the red rice parent. Hybrids produced 20-50% more seed than the rice parent, but had equivalent seed production to the majority of red rice parents. Seeds of all hybrids were red, pubescent and dehisced at maturity. For the majority of hybrids, seed germination was higher than that of the red rice parent. The gene flowrate from red rice to rice was 0.01-0.2% and differed by red rice biotype. The hybrids had higher fecundity and potential competitive ability than the rice parent, and in some cases also the red rice parent. Red rice plants are vectors of gene flow back to cultivated rice and other weedy populations. The progeny of red rice hybrids from cultivated rice mother plants have higher chances of persistence than those from red rice mother plants. Gene flow mitigation strategies should consider this scenario. Copyright 2009 Society of Chemical Industry.

  1. Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

    PubMed Central

    Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

    2008-01-01

    The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

  2. Molecular identification of coagulase-negative staphylococci isolated from bovine mastitis and detection of β-lactam resistance.

    PubMed

    Srednik, Mariela Elizabeth; Grieben, Mario Andres; Bentancor, Adriana; Gentilini, Elida Raquel

    2015-09-27

    Bovine mastitis is a frequent cause of economic loss in dairy herds. Coagulase-negative staphylococci (CoNS) are increasing in importance as causeof bovine intramammary infection (IMI) throughout the world in recent years. CoNShave been isolated from milk samples collected from cows with clinical andsubclinical mastitis in several countries. Identification of mastitis pathogensis important when selection appropriate antimicrobial therapy. A total of 93 strains of Staphylococcusspp isolated from bovine clinical andsubclinical mastitis in Argentina during 2010-2013 were identified by Restriction Fragment Length Polymorphism (RFLP)-PCR using the gap gene. The isolates were tested by PCR for the presence of blaZ gene and mecA gene and were tested by disk diffusion for the susceptibilityto penicillin and cefoxitin. The most common CoNS species was S.chromogenes 46.2% (43/93), followed by S. devriesei 11.8% (11/93) and S. haemolyticus 9.7% (9/93). The blaZ gene was detected in 19 (20.4%) but only 16 (17.2%) isolates were resistant to penicillin; the mecA was detected in6 (6.5%) isolates but only 4 (4.3) were resistant to cefoxitin. The 6 mecA-positive isolates showed oxaxillinMICs ≤ 0.5 μg/ml. CoNSare important minor mastitis pathogens and can be the cause of substantial economic losses. Despite the low resistance to PEN in Argentina, the presenceof MR isolates found in this study emphasize the importance of identificationof CoNS when an IMI is present because of the potentially risk of lateraltransfer of resistance genes between staphylococcal species.

  3. Therapeutic effect of polysaccharide fraction of Atractylodis macrocephalae Koidz. in bovine subclinical mastitis.

    PubMed

    Xu, Wei; Guan, Ran; Lu, Yisong; Su, Xiaoyan; Xu, Ye; Du, Aifang; Hu, Songhua

    2015-07-25

    Mastitis is considered the most significant and persistent disease in dairy cows, bringing about large economic losses. Subclinical mastitis brings about major cost implications, for it is difficult to detect due to absence of any visible indications and can persist in the mammary tissue throughout lactation. Immunomodulators have been widely used to reduce intramammary infections by modulating bovine mammary gland. Atractylodis macrocephalae Koidz. polysaccharides (RAMP), extracted from herbal medicine, has been used widely especially for its immunomodulatory function for many years. The objective of this study was to estimate an oil emulsified Atractylodis macrocephalae Koidz. polysaccharides (RAMP-O) as a potential therapeutic agent to treat subclinical mastitis by subcutaneous injection of RAMP-O in the area of supramammary lymph node in lactating cows via analysis of SCC, IMIs and NAGase. Injection of RAMP-O in the area of supramammary lymph node significantly reduced milk SCC and NAGase activity compared with control. The quarters with bacterial infection were also progressively reduced in RAMP-O treated cows and only 9 quarters were found to have bacterial infection, while no obvious change was found in the control group. Subcutaneous injection of RAMP-O in the area of supramammary lymph node had therapeutic value in the treatment of bovine subclinical mastitis by reducing SCC, NAGase and IMIs in milk. Considering both the therapeutic effect and the cost of RAMP-O, 32 mg per dose was found most suitable to reduce milk SCC and NAGase. Therefore, RAMP-O deserves further study for its use in treatment of bovine mastitis.

  4. Effect of mid-line or low-line milking systems on milking characteristics in goats.

    PubMed

    Manzur, Alberto; Díaz, José-Ramón; Mehdid, Amine; Fernández, Nemesio; Peris, Cristòfol

    2012-08-01

    Two experiments were carried out to compare mechanical milking in mid-level (ML) and low-level (LL) milkline in goats. The first trial used 40 intramammary infection (IMI)-free goats that had been milked in ML during a pre-experimental period of 4±1 weeks post partum. These animals were divided into two groups (n=20), randomly assigning each group to ML or LL milking for a 17-week experimental period. During this period, several strategies were applied to increase teat exposure to pathogens in both experimental groups. The IMI rate was the same in both experimental groups (30% of goats), although the majority of new infections appeared earlier in ML (weeks 1-5) than in LL (weeks 7-16). Teat-end vacuum range (maximum minus minimum vacuum) was higher in ML than in LL, but no significant differences were found in the remaining variables [milk production and composition, somatic cell count (SCC), frequency of liner slips+teatcups fall off]. In the second experiment, in a crossover design (54 goats in fourth month of lactation; 2 treatments, ML and LL, in 2 experimental periods each lasting 1 week) it was observed that both the milk fractioning (reduced machine milk and increased machine stripping) and average machine milk flow worsened slightly in ML milking; in contrast, no differences were observed in total milking time or teat thickness changes after milking. It was concluded that the differences found between ML and LL are not sufficiently important to discourage breeders from using ML in goat milking.

  5. Right ventricular myocardial infarction: presentation and acute outcomes.

    PubMed

    Chockalingam, Anand; Gnanavelu, G; Subramaniam, T; Dorairajan, Smrita; Chockalingam, V

    2005-01-01

    Acute inferior wall myocardial infarction can be complicated by right ventricular myocardial infarction (RVMI), and the excess mortality cannot be fully explained by mechanical reasons. The authors try to systematically assess the incidence, clinical presentation and early outcomes of right ventricular infarction in a tertiary-care setup. Their study was a prospective observational series of consecutive patients with RVMI. All patients with acute inferior myocardial infarction (n=135) were enlisted. RVMI was diagnosed by > or = 1 mm ST elevation in lead V(4R) in a right-sided electrocardiogram. Right ventricular (RV) infarction occurred in 37% (n=50) of patients with acute inferior infarctions. Patients with isolated inferior infarction served as controls (n=85). Echocardiography was performed within 24 hours of admission. From both groups, 66% qualified for thrombolysis. The incidence of hypotension-bradycardia and heart blocks requiring pacing support was much higher in right ventricular infarction (n=21) than in inferior infarction (n=13). Clinically manifest RV dysfunction (raised jugular venous pulse [JVP], hypotension, tricuspid regurgitation) and right ventricular dilation detected by echocardiography were seen in only 13 patients. The in-hospital mortality rate was significantly higher (n=8, 16%) in right ventricular infarction group than in inferior infarction group (n=3, 3.5%). Right ventricular infarction was seen in a third of inferior myocardial infarctions (IMIs), but hemodynamically evident right ventricular dysfunction occurred in only a tenth of acute IMIs. Nevertheless, the acute in-hospital mortality rate of patients with right ventricular infarction was much higher than in those with inferior infarction owing to arrhythmic and mechanical complications.

  6. Production and processing of Metarhizium anisopliae var. acridum submerged conidia for locust and grasshopper control.

    PubMed

    Kassa, Adane; Stephan, Dietrich; Vidal, Stefan; Zimmermann, Gisbert

    2004-01-01

    Currently, mycopesticide development for locust and grasshopper control depends on aerial conidia or submerged spores of entomopathogenic fungi. In our study, the production of submerged conidia of Metarhizium anisopliae var. acridum (IMI 330189) was investigated in a liquid medium containing 3% biomalt and 1% yeast extract (BH-medium). The effects of freeze and spray drying techniques on the quality of submerged conidia were determined. The influence of different additives on the viability of fresh submerged conidia and their suitability for oil flowable concentrate formulation development was assessed. In a BH medium maintained at 180 rev min(-1), at 30 degrees C for 72 h, IMI 330189 produced a green pigmented biomass of submerged conidia whereas in Adámek medium it produced a yellowish biomass of submerged spores. The spore concentration was high in both media; however, the size of the spores produced in the BH medium was significantly lower than those produced in Adámek medium (P < 0.001). Submerged conidia can be effectively dried using either freeze or spray drying techniques. The viability and speed of germination were significantly affected by the drying and pulverizing process (P < 0.001). The initial viability was significantly higher for spray-dried submerged conidia than for freeze-dried spores. Pulverizing of freeze-dried submerged conidia reduced the speed of germination and the viability by 63-95%. Dried submerged conidia can be stored over 45 wk at low temperatures (< 10 degrees) without suffering a significant loss in viability. Furthermore, we have identified carriers that are suitable for oil flowable concentrate formulation development.

  7. Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

    PubMed

    Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

    2018-01-01

    Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

  8. Patterning of OPV modules by ultra-fast laser

    NASA Astrophysics Data System (ADS)

    Kubiš, Peter; Lucera, Luca; Guo, Fei; Spyropolous, George; Voigt, Monika M.; Brabec, Christoph J.

    2014-10-01

    A novel production process combining slot-die coating, transparent flexible IMI (ITO-Metal-ITO) electrodes and ultra-fast laser ablation can be used for the realization of P3HT:PCBM based thin film flexible OPV modules. The fast and precise laser ablation allows an overall efficiency over 3 % and a device geometric fill factor (GFF) over 95 %. Three functional layers can be ablated using the same wavelength only with varying the laser fluence and overlap. Different OPV device architectures with multilayers utilizing various materials are challenging for ablation but can be structured by using a systematical approach.

  9. Self-Diagnosing Design Techniques.

    DTIC Science & Technology

    1978-06-30

    architecture, functional parti, .onin-, and llodulE and component features on nicroprogranmable self diagnosing capabilit es of digitat processors were...the v wish to transmit . Should the proess5or that was t1 receive I i-"sageswi tch to the transmit statte at the( sanme t imie as tlhe 11(’St p)roe es ...I I S" 1 M i I) S. C. C7. 1110, ME W()III I{I{Ji C( )l. \\\\’t ll)j)* (A (I (" P. I{" Hi it INT I IR, I - --V 11111 1 1 1.] S i RUMW :𔃼 A ES I; TFUST

  10. A Structural Weight Estimation Program (SWEEP) for Aircraft. Volume 6 - Wing and Empennage Module. Appendix C: Program Flow Charts, Overlays (9.0) and (10,0)

    DTIC Science & Technology

    1974-06-01

    NQUI II.CH Uj^f^i.»! orwi MI-../f;*« MA orrrtAi IOHAI niuipi imiAi mioi tu U/IN IK «»At IB MIDI win» t np roKnAi im fx.ir...rj0lll.f<CC9>l,(DCUI.II??)l. ICKi«. TDOUIfi I, IK . >’. TlKWi Si I. l!Ü>X. lOKJrs I). ( WAV .rtXO»». ((;XW.»;)(*>.U.(KlMi)(ClH.MOP|.rt)(a’M, lWM3i

  11. Thermal Stability of Gun Propellants from Munition Articles That Returned from Cambodia.

    DTIC Science & Technology

    1998-02-01

    0482 0661 0312 0472 EMZ 79- 11 MEN 80-8 DAG 86-2 MEN 88-57 DAG 89- 11 DAG 90-3 IMI91-4 7% 9 % 12% 15% 17% 18% 16% CTG.50 inch Ball LKD...5. Peltierelement, 6. diffe- rentiemeetpunt, 7. aluminium binnenblok, 8. referentievat, 9 . isolatie, 10. verwarmingsman- tel, 11 . isolatie, 12...W/TR CTG 7,62 mm NATO Ball CTG.50 inch Med RNG Ball LKD, W/TR CTG 7,62 mm NATO Ball CTG 9 mm NATO Ball CTG 7,62 mm NATO Ball CTG 7,62 mm NATO

  12. Diagnosing cystic fibrosis in newborn screening in Poland - 15 years of experience.

    PubMed

    Sands, Dorota; Zybert, Katarzyna; Mierzejewska, Ewa; Ołtarzewski, Mariusz

    2015-01-01

    Early diagnosis of cystic fibrosis (CF) made by the introduction of CF NBS (Cystic Fibrosis Newborn Screening) provides the opportunity to undertake preventive measures and provide treatment before the development of irreversible changes in the respiratory tract and other complications. CF NBS was conducted as a pilot programme in four Polish districts in the period 1999-2003. In 2006 CF NBS started again and was gradually extended across the country. The aim of this study was to show the evolution of the Polish CF NBS strategies and assess the diagnostic consequences of this programme. The study involved children diagnosed and treated only in the IMiD Centre. The strategy in Polish CF NBS was modified over time. Firstly, the model IRT/IRT and IRT/IRT/DNA with one mutation was implemented, which was followed by IRT/DNA with a gradually expanding number of CFTR mutations (tab. I). Newborns with positive results of CF NBS were called to the CF IMiD Centre, and sweat tests were performed. The children diagnosed and children with mutations in both alleles of the CFTR gene even if at least one of them had undefined pathogenicity) were taken under IMiD Centre care. Sensitivity, specificity and positive predictive values during subsequent stages of CF NBS were calculated (tab. III). During the 1999-2003 pilot study 444 063 newborns underwent CF NBS and in 74 cases CF was diagnosed. 582 693 newborns were screened from September 2006 to December 2011 in four regions and 100 children were diagnosed with CF. The frequencies of CF in the Polish population in both screening periods were 1:5767 and 1:5712 respectively. Firstly, the IRT/IRT model was implemented, but the number of newborns called to the CF Centre was high - the PPV was 7.6%. In the next step CF NBS DNA analysis was used. Here sensitivity and specificity were high - nearly 100%. In the following years the number of mutations detected was expanded (including 16 most common ones in the Polish population). Due to the panel changes, the number of calls declined and the PPV (predictive positive value) improved (to 26.1%) after the application of expanded genetic analysis. Expanding the panel of mutations resulted in an increased number of carriers and observational subjects. IRT/DNA strategy with expanded DNA analysis provides the opportunity for earlier CF diagnosis even in children with normal sweat test values. However, this model caused frequent carrier detection and inconclusive diagnosis in comparison to IRT/IRT or IRT/IRT/DNA with a limited number of mutations. Further research and changes in Polish CF NBS are needed to increase the PPV, while preserving high sensitivity and specificity..

  13. Identification of virulence factors in 16S-23S rRNA intergenic spacer genotyped Staphylococcus aureus isolated from water buffaloes and small ruminants.

    PubMed

    Cremonesi, P; Zottola, T; Locatelli, C; Pollera, C; Castiglioni, B; Scaccabarozzi, L; Moroni, P

    2013-01-01

    Staphylococcus aureus is an important human and animal pathogen, and is regarded as an important cause of intramammary infection (IMI) in ruminants. Staphylococcus aureus genetic variability and virulence factors have been well studied in veterinary medicine, especially in cows as support for control and management of IMI. The aim of the present study was to genotype 71 Staph. aureus isolates from the bulk tank and foremilk of water buffaloes (n=40) and from udder tissue (n=7) and foremilk (n=24) from small ruminants. The method used was previously applied to bovine Staph. aureus and is based on the amplification of the 16S-23S rRNA intergenic spacer region. The technique applied was able to identify different Staph. aureus genotypes isolated from dairy species other than the bovine species, and cluster the genotypes according to species and herds. Virulence gene distribution was consistent with genotype differentiation. The isolates were also characterized through determination of the presence of 19 virulence-associated genes by specific PCR. Enterotoxins A, C, D, G, I, J, and L were associated with Staph. aureus isolates from buffaloes, whereas enterotoxins C and L were linked to small ruminants. Genes coding for methicillin resistance, Panton-Valentine leukocidin, exfoliative toxins A and B, and enterotoxins B, E, and H were undetected. These findings indicate that RNA template-specific PCR is a valid technique for typing Staph. aureus from buffaloes and small ruminants and is a useful tool for understanding udder infection epidemiology. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.

    PubMed

    Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

    2014-08-01

    The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery.

  15. Using electronic health records for clinical research: the case of the EHR4CR project.

    PubMed

    De Moor, Georges; Sundgren, Mats; Kalra, Dipak; Schmidt, Andreas; Dugas, Martin; Claerhout, Brecht; Karakoyun, Töresin; Ohmann, Christian; Lastic, Pierre-Yves; Ammour, Nadir; Kush, Rebecca; Dupont, Danielle; Cuggia, Marc; Daniel, Christel; Thienpont, Geert; Coorevits, Pascal

    2015-02-01

    To describe the IMI EHR4CR project which is designing and developing, and aims to demonstrate, a scalable, widely acceptable and efficient approach to interoperability between EHR systems and clinical research systems. The IMI EHR4CR project is combining and extending several previously isolated state-of-the-art technical components through a new approach to develop a platform for reusing EHR data to support medical research. This will be achieved through multiple but unified initiatives across different major disease areas (e.g. cardiovascular, cancer) and clinical research use cases (protocol feasibility, patient identification and recruitment, clinical trial execution and serious adverse event reporting), with various local and national stakeholders across several countries and therefore under various legal frameworks. An initial instance of the platform has been built, providing communication, security and terminology services to the eleven participating hospitals and ten pharmaceutical companies located in seven European countries. Proof-of-concept demonstrators have been built and evaluated for the protocol feasibility and patient recruitment scenarios. The specifications of the clinical trial execution and the adverse event reporting scenarios have been documented and reviewed. Through a combination of a consortium that brings collectively many years of experience from previous relevant EU projects and of the global conduct of clinical trials, of an approach to ethics that engages many important stakeholders across Europe to ensure acceptability, of a robust iterative design methodology for the platform services that is anchored on requirements of an underlying Service Oriented Architecture that has been designed to be scalable and adaptable, EHR4CR could be well placed to deliver a sound, useful and well accepted pan-European solution for the reuse of hospital EHR data to support clinical research studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Oral biopharmaceutics tools - time for a new initiative - an introduction to the IMI project OrBiTo.

    PubMed

    Lennernäs, H; Aarons, L; Augustijns, P; Beato, S; Bolger, M; Box, K; Brewster, M; Butler, J; Dressman, J; Holm, R; Julia Frank, K; Kendall, R; Langguth, P; Sydor, J; Lindahl, A; McAllister, M; Muenster, U; Müllertz, A; Ojala, K; Pepin, X; Reppas, C; Rostami-Hodjegan, A; Verwei, M; Weitschies, W; Wilson, C; Karlsson, C; Abrahamsson, B

    2014-06-16

    OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Microstructurally based variations on the dwell fatgue life of titanium alloy IMI 834

    NASA Technical Reports Server (NTRS)

    Thomsen, Mark L.; Hoeppner, David W.

    1994-01-01

    An experimental study was undertaken to determine the role of microstructure on the fatigue life reduction observed in titanium alloy IMI 834 under dwell loading conditions. The wave forms compared were a trapezoid with 15 and 30 second hold times at the maximum test load and a baseline, 10 Hertz, haversine. The stress ratio for both loading wave forms was 0.10. The fatigue loading of each specimen was conducted in a vacuum within a scanning electron microscope chamber which minimized the possibility that the laboratory environment would adversely affect the material behavior. Two microstructural conditions were investigated in the experimental program. The first involved standard 'disk' material with equiaxed alpha in a transformed beta matrix. The second material was cut from the same disk forging as the first but was heat treated to obtain a martensitic alpha prime microstructure. Tensile tests were performed prior to the onset of the fatigue loading portion of the study, and it was determined that the yield strengths of the specimens from both material conditions were within ten percent. The maximum fatigue loads were chosen to be 72 percent of the average yield strength for both materials as determined from the tensile tests. It was found that the cycles to failure from the 10 Hertz loading wave form were reduced by a factor of approximately five when the loading was changed to the trapezoidal wave form for the standard 'disk' material. The fatigue life reduction for the martensitic structure under identical test conditions was approximately 1.75. The improvement observed with the martensitic structure also was accompanied by an increase in overall fatigue life for the wave forms tested. This paper will review the results and conclusions of this effort.

  18. Motivation, expectations, and usability of a driven gait orthosis in stroke patients and their therapists.

    PubMed

    Swinnen, Eva; Lefeber, Nina; Willaert, Ward; De Neef, Fallon; Bruyndonckx, Lyn; Spooren, Annemie; Michielsen, Marc; Ramon, Tine; Kerckhofs, Eric

    2017-05-01

    In the development of efficacious driven gait orthoses (DGO), it is an added value to consider patients' and therapists' perspectives concerning robot-assisted gait training (RAGT). A better understanding of these issues may improve the process of care and outcome. This study aimed to examine stroke patients' motivation and expectations of RAGT, and therapists' expectations and perspectives on the usability of RAGT. Additionally, the differences in expectations between stroke patients and their therapists were analyzed. A cross sectional, multi-center, three-group trial was conducted. Included were (1) stroke patients who have experience with RAGT (i.e. the stroke user group), (2) stroke patients who have no experience with RAGT (i.e. the stroke non-user group), and (3) therapists who have experience with RAGT (i.e. the therapist user group). The Intrinsic Motivation Inventory (IMI), Credibility/Expectancy Questionnaire (CEQ), and Usefulness, Satisfaction and Ease of Use Questionnaire (USE) were used. Descriptive statistics and non-parametric Kruskal-Wallis tests were conducted. In total, 46 subjects were assessed (stroke user group: n = 23, stroke non-user group: n = 14, therapist user group: n = 9). IMI subscale scores ranged from 42 to 88%. Mean credibility and expectancy ranged from 80 to 85% and 57 to 72%, respectively, with no significant differences between groups. USE subscale scores ranged from 61 to 72%. Stroke user group patients seem quite motivated to train with the DGO and both patients and therapists reasonably believe that this training could improve gait functioning. Therapists are moderately satisfied with the usability of the DGO, but there is room for improvement with respect to usefulness and ease of use.

  19. Robot-assisted task-oriented upper extremity skill training in cervical spinal cord injury: a feasibility study.

    PubMed

    Vanmulken, D A M M; Spooren, A I F; Bongers, H M H; Seelen, H A M

    2015-07-01

    Prospective multiple case study. To test (1) the feasibility of haptic robot technology (Haptic Master (HM)) use to improve arm-hand function (AHF) and arm-hand skill performance (AHSP) in persons with a cervical spinal cord injury (C-SCI), (2) inventory participants' motivation and expectation to work with the robot technology used and (3) to descriptively report the results in individual cases. Rehabilitation Centre. Five C-SCI patients were trained for 6 weeks, 3 days per week, 60 min per day. Therapists filled out the Usefulness, Satisfaction and Ease-of-use questionnaire (USE). The Intrinsic Motivational Inventory (IMI) and credibility and expectancy questionnaire (CEQ) were filled out by participants. Performance at activity level was gauged using the Van Lieshout test for AHF in Tetraplegia and the Spinal Cord Independence Measure. Function level was gauged using muscle strength testing and the International Classification for Surgery of the Hand in Tetraplegia. As to the feasibility of the application of haptic robot technology, the mean USE score was 65%. Mean IMI and CEQ results were 67% and 60%, respectively. Participants were motivated to train with the HM. All participants rated credibility higher than expectations regarding the improvement. In the current patients, little progress was demonstrated at the International Classification of Functioning, Disability and Health function and the activity level. It is feasible to train C-SCI persons with the HM. Therapists report that working with the HM is easy to learn and easy to perform. Usability of the HM may be improved. Further research is needed to assess in which group of C-SCI and at which stage of rehabilitation HM training may be most beneficial.

  20. Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

    PubMed

    Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

    2015-09-01

    Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). © 2015 British Society for Immunology.

  1. Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

    PubMed Central

    Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

    2015-01-01

    Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; http://www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; http://www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). PMID:25959571

  2. Effects of subinhibitory concentrations of antimicrobial agents on Escherichia coli O157:H7 Shiga toxin release and role of the SOS response.

    PubMed

    Nassar, Farah J; Rahal, Elias A; Sabra, Ahmad; Matar, Ghassan M

    2013-09-01

    Treatment of Escherichia coli O157:H7 by certain antimicrobial agents often exacerbates the patient's condition by increasing either the release of preformed Shiga toxins (Stx) upon cell lysis or their production through the SOS response-triggered induction of Stx-producing prophages. Recommended subinhibitory concentrations (sub-MICs) of azithromycin (AZI), gentamicin (GEN), imipenem (IMI), and rifampicin (RIF) were evaluated in comparison to norfloxacin (NOR), an SOS-inducer, to assess the role of the SOS response in Stx release. Relative expression of recA (SOS-inducer), Q (late antitermination gene of Stx-producing prophage), stx1, and stx2 genes was assessed at two sub-MICs of the antimicrobials for two different strains of E. coli O157:H7 using reverse transcription-real-time polymerase chain reaction. Both strains at the two sub-MICs were also subjected to Western blotting for LexA protein expression and to reverse passive latex agglutination for Stx detection. For both strains at both sub-MICs, NOR and AZI caused SOS-induced Stx production (high recA, Q, and stx2 gene expression and high Stx2 production), so they should be avoided in E. coli O157:H7 treatment; however, sub-MICs of RIF and IMI induced Stx2 production in an SOS-independent manner except for one strain at the first twofold dilution below MIC of RIF where Stx2 production decreased. Moreover, GEN caused somewhat increased Stx2 production due to its mode of action rather than any effect on gene expression. The choice of antimicrobial therapy should rely on the antimicrobial mode of action, its concentration, and on the nature of the strain.

  3. Scope of Work for Integration Management and Installation Services of the National Ignition Facility Beampath Infrastructure System

    NASA Astrophysics Data System (ADS)

    Coyle, P. D.

    2000-03-01

    The goal of the National Ignition Facility (NIF) project is to provide an above ground experimental capability for maintaining nuclear competence and weapons effects simulation and to provide a facility capable of achieving fusion ignition using solid-state lasers as the energy driver. The facility will incorporate 192 laser beams, which will be focused onto a small target located at the center of a spherical target chamber-the energy from the laser beams will be deposited in a few billionths of a second. The target will then implode, forcing atomic nuclei to sufficiently high temperatures and densities necessary to achieve a miniature fusion reaction. The NIF is under construction, at Livermore, California, located approximately 50 miles southeast of San Francisco, California. The University of California, Lawrence Livermore National Laboratory (LLNL), operating under Prime Contract W-7405-ENG. 48 with the U.S. Department of Energy (DOE), shall subcontract for Integration Management and Installation (IMI) Services for the Beampath Infrastructure System (BIS). The BIS includes Beampath Hardware and Beampath Utilities. Conventional Facilities work for the NIF Laser and Target Area Building (LTAB) and Optics Assembly Building (OAB) is over 86 percent constructed. This Scope of Work is for Integration Management and Installation (IMI) Services corresponding to Management Services, Design Integration Services, Construction Services, and Commissioning Services for the NIB BIS. The BIS includes Beampath Hardware and Beampath Utilities. Beampath Hardware and Beampath Utilities include beampath vessels, enclosures, and beam tubes; auxiliary and utility systems; and support structures. A substantial amount of GFE will be provided by the University for installation as part of the infrastructure packages.

  4. Isolation and partial characterization of a mutant of Penicillium funiculosum for the saccharification of straw

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoffman, R.M.; Wood, T.M.

    1985-01-01

    Clearing of agar plates containing ball-milled, delignified straw has been used for screening mutants of Penicillium funiculosum IMI 87160 III. The effects of glycerol and a number of sugars on the clearing were investigated for selecting derepressed mutants. The ..beta..-glucosidase synthesis by one such mutant, C22c, in shake flasks containing straw was not repressed by 5% glycerol, whereas activities on filter paper, CM-cellulose, and p-nitrophenyl-..beta..-xylosidase were only partially derepressed; xylanase was extensively derepressed. The evidence for separate control of the enzymes involved in the solubilization of straw is discussed. 23 references.

  5. Purification of the major endoglucanase from Aspergillus fumigatus Fresenius.

    PubMed

    Parry, J B; Stewart, J C; Heptinstall, J

    1983-08-01

    Aspergillus fumigatus (Fresenius), IMI 246651, A.T.C.C. 46324, produces two beta-glucosidase enzymes, cotton-solubilizing activity, xylanase and endoglucanase enzymes which can be separated by gel-filtration chromatography. The major endoglucanase does not bind to concanavalin A-Sepharose and does not stain with periodic acid/Schiff reagent. It is homogeneous on polyacrylamide isoelectric focusing (pI = 7.1) and has a mol.wt. of 12500 by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The endoglucanase produces glucose and a mixture of oligosaccharides from cellulose; the purified enzyme has a small dextranase activity. It is stable at 50 degrees C and pH 6.

  6. The Shock and Vibration Bulletin. Part 3. Analytical Methods, Dynamic Analysis, Vehicle Systems

    DTIC Science & Technology

    1981-05-01

    1 Strnge Spcingramtr Fig 3% aito fma qaedslcmn ihsrne pcn 654 12 100 0 0 0 4 0 s 0 2 Distance along peal edge in - - Fig. 4 - Variation of...7 ~ ! v’j 4 pq -1 iijiL - -bp(C) I bpp ’ (24) L V* ki k2K 2 + (1 (ZT~~ - !I + !- 2) Y(IJ) and the value of bpp ’ can be tabulated as in 101 L .’blel1I...mI Table It. Values of bpp in Equation (24) The assembling of equations for a gun dynamics problem is more involved. The basic r1 procedures

  7. Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Air Force Plant 4, Fort Worth, Texas. Volume 5. Appendix A-2.

    DTIC Science & Technology

    1987-12-01

    Limit Spiked Samale Samole ISailced C" auod R sIus’lt (SSR) esult. (SR) A-dded ( .SA) Iels: I. I 1. A.luminum 75-125 - I Z. Antimony - 3. Arsenic " I...UntKtarix *s %Control Limit Spiked Samale Sample SieiCm.,ound _ _R R esult (SSR) Re t,.- (SR) Added (SA) Z,10 1. AUlunu m 7 I I I 2. Antimonyj ____ 3...No. DATE Lab Sample) ;S4 No Katrix waot, " . n ...Central L imi Spiked Samale Samale Spiked Comnpound M Rsult: (SSR) Result (SR) jAdded (SA) XR

  8. Aflatoxin in detannin coffee and tea and its destruction.

    PubMed

    Hasan, H A H

    2002-05-01

    The aflatoxins produced byAspergillus parasiticus var. globosus IMI 12090 in detannin-caffeinated coffee and black tea were five times more concentrated than in regular coffee and tea. The activity of caffeine and tannin on the fungus growth and aflatoxin production in liquid broth was tested at three levels: viz. 0.1, 0.3, and 0.6%. Tannin and caffeine induced 95% inhibition in aflatoxins at 0.3% and 0.6%, respectively. The antiaflatoxigenic properties of regular coffee and tea appear to be due to tannin, followed by caffeine. The roasting of contaminated coffee beans at 200 degrees C for 20 min is effective in the destruction of aflatoxins.

  9. Fragility issues of medical video streaming over 802.11e-WLAN m-health environments.

    PubMed

    Tan, Yow-Yiong Edwin; Philip, Nada; Istepanian, Robert H

    2006-01-01

    This paper presents some of the fragility issues of a medical video streaming over 802.11e-WLAN in m-health applications. In particular, we present a medical channel-adaptive fair allocation (MCAFA) scheme for enhanced QoS support for IEEE 802.11 (WLAN), as a modification for the standard 802.11e enhanced distributed coordination function (EDCF) is proposed for enhanced medical data performance. The medical channel-adaptive fair allocation (MCAFA) proposed extends the EDCF, by halving the contention window (CW) after zeta consecutive successful transmissions to reduce the collision probability when channel is busy. Simulation results show that MCAFA outperforms EDCF in-terms of overall performance relevant to the requirements of high throughput of medical data and video streaming traffic in 3G/WLAN wireless environments.

  10. Decreasing Indian summer monsoon on the northern Indian sub-continent during the last 180 years: evidence from five tree-ring cellulose oxygen isotope chronologies

    NASA Astrophysics Data System (ADS)

    Xu, Chenxi; Sano, Masaki; Priyadarshan Dimri, Ashok; Ramesh, Rengaswamy; Nakatsuka, Takeshi; Shi, Feng; Guo, Zhengtang

    2018-05-01

    We have constructed a regional tree-ring cellulose oxygen isotope (δ18O) record for the northern Indian sub-continent based on two new records from northern India and central Nepal and three published records from northwestern India, western Nepal and Bhutan. The record spans the common interval from 1743 to 2008 CE. Correlation analysis reveals that the record is significantly and negatively correlated with the three regional climatic indices: all India rainfall (AIR; r = -0.5, p < 0.001, n = 138), Indian monsoon index (IMI; r = -0.45, p < 0.001, n = 51) and the intensity of monsoonal circulation (r = -0.42, p < 0.001, n = 51). The close relationship between tree-ring cellulose δ18O and the Indian summer monsoon (ISM) can be explained by oxygen isotope fractionation mechanisms. Our results indicate that the regional tree-ring cellulose δ18O record is suitable for reconstructing high-resolution changes in the ISM. The record exhibits significant interannual and long-term variations. Interannual changes are closely related to the El Niño-Southern Oscillation (ENSO), which indicates that the ISM was affected by ENSO in the past. However, the ISM-ENSO relationship was not consistent over time, and it may be partly modulated by Indian Ocean sea surface temperature (SST). Long-term changes in the regional tree-ring δ18O record indicate a possible trend of weakened ISM intensity since 1820. Decreasing ISM activity is also observed in various high-resolution ISM records from southwest China and Southeast Asia, and may be the result of reduced land-ocean thermal contrasts since 1820 CE.

  11. Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib.

    PubMed

    Brümmendorf, Tim H; Cortes, Jorge E; Khoury, Hanna J; Kantarjian, Hagop M; Kim, Dong-Wook; Schafhausen, Philippe; Conlan, Maureen G; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Gambacorti-Passerini, Carlo; Lipton, Jeff H

    2016-01-01

    The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long-term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)-resistant (IM-R; n = 196)/IM-intolerant (IM-I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow-up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53-65%); Kaplan-Meier (KM) probability of maintaining MCyR at 4 years was 75% (66-81%). Cumulative incidence of on-treatment progression/death at 4 years was 19% (95% CI, 15-24%); KM 2-year overall survival was 91% (87-94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib-sensitive BCR-ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver-related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM-R/IM-I CP-CML patients. © 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

  12. Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics.

    PubMed

    Willenbacher, Ella; Weger, Roman; Rochau, Ursula; Siebert, Uwe; Willenbacher, Wolfgang

    2016-01-01

    Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011-2014, 21% in patients with a diagnosis made between 2000-2005, and 39% in those with a diagnosis made between 2006-2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide-so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM.

  13. Effect of different scenarios for selective dry-cow therapy on udder health, antimicrobial usage, and economics.

    PubMed

    Scherpenzeel, C G M; den Uijl, I E M; van Schaik, G; Riekerink, R G M Olde; Hogeveen, H; Lam, T J G M

    2016-05-01

    The goal of dry-cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antimicrobials has become questionable. In this study, we evaluated the effects of 8 scenarios for selecting animals for DCT, taking into account variation in parity and cow-level somatic cell count (SCC) at drying off. The aim of this study was to evaluate udder health, antimicrobial usage, and economics at the herd level when using different scenarios for selecting cows for DCT. To enable calculation and comparison of the effects of different scenarios to select cows for DCT in an "average" herd, we created an example herd, with a virtual herd size of 100 dairy cows to be calving during a year. Udder health, antimicrobial usage, and economics were evaluated during the dry period and the first 100 d in lactation, the period during which the greatest effect of DCT is expected. This leads to an estimated 13,551 cow-days at risk during a year in a 100-cow dairy herd. In addition to a blanket DCT (BDCT) scenario, we developed 7 scenarios to select cows for DCT based on SCC. The scenarios covered a range of possible approaches to select low-SCC cows for DCT, all based on cow-level SCC thresholds on the last milk recording before drying off. The incidence rate of clinical mastitis in the example herd varied from 11.6 to 14.5 cases of clinical mastitis per 10,000 cow-days at risk in the different scenarios, and the prevalence of subclinical mastitis varied from 38.8% in scenario 1 (BDCT) to 48.3% in scenario 8. Total antimicrobial usage for DCT and clinical mastitis treatment varied over the scenarios from 1.27 (scenario 8) to 3.15 animal daily dosages (BDCT), leading to a maximum reduction in antimicrobial usage of 60% for scenario 8 compared with BDCT. The total costs for each of the scenarios showed little variation, varying from €4,893 for scenario 5 to €5,383 for scenario 8. The effect of selective DCT compared with BDCT on udder health, antimicrobial usage, and economics is influenced by the SCC criteria used to select cows for DCT. Scenario 2 resulted in the lowest increases in clinical and subclinical mastitis compared with BDCT. The greatest reduction in antimicrobial usage was achieved under scenario 8. From an economic perspective, lowest costs were achieved with scenario 5. Drying off dairy cows with antimicrobials has an effect on udder health, antimicrobial usage, and economics. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Anoplastie périnéale simple pour le traitement des malformations anorectales basses chez l'adulte, à propos de deux cas

    PubMed Central

    Echchaoui, Abdelmoughit; Benyachou, Malika; Hafidi, Jawad; Fathi, Nahed; Mohammadine, Elhamid; ELmazouz, Samir; Gharib, Nour-eddine; Abbassi, Abdellah

    2014-01-01

    Les malformations anorectales chez l'adulte sont des anomalies congénitales rares du tube digestif qui prédominent chez le sexe féminin. Notre étude porte sur deux observations de malformation anorectale basses vues et traitées au stade adulte par les 2 équipes (plasticiens et viscéralistes) à l'Hôpital Avicenne à Rabat. Il s'agit d'un homme de 24 ans avec une dyschésie anale l'autre cas est une femme de 18 ans avec une malformation anovulvaire Les caractéristiques cliniques combinées avec les imageries radiologiques (lavement baryté, et la manométrie anorectale) ont confirmé qu'il s'agit d'une malfomation anorectale basse. Les deux cas sont corrigés par une reconstruction sphinctérienne, réimplantation anale avec anoplastie périnéale. Les suites opératoires étaient simples, pas de souffrance cutanée ou nécrose, avec changement de pansement gras chaque jour. Le résultat fonctionnel (la continence) était favorable pour les 2 patients. La présentation des MAR à l’âge adulte est rare, d’étiologie mal connu, elles apparaissent selon le mode sporadique. Les caractéristiques cliniques, couplées à l'imagerie (lavement baryté, IRM pelvienne), l'endoscopie et la manométrie anorectale, permettent de confirmer le diagnostic et classer ces anomalies en 3 types: basses, intermédiaires, et hautes. Les formes basses sont traités d'emblée par une réimplantation anale et anoplastie périnéale simple tels nos deux cas, elles peuvent être traités dans certains cas par un abaissement anorectale associé à une plastie V-Y permettant ainsi un emplacement anatomique correct de l'anus; alors que les formes hautes ou intermédiaires relèvent d'une chirurgie complexe avec souvent une dérivation digestive transitoire. Contrairement aux autres formes, Les formes basses ont un pronostic fonctionnel favorable. PMID:25667689

  15. Reciprocal combinations of barley and corn grains in oil-supplemented diets: feeding behavior and milk yield of lactating cows.

    PubMed

    Kargar, S; Ghorbani, G R; Khorvash, M; Sadeghi-Sefidmazgi, A; Schingoethe, D J

    2014-11-01

    The effect of barley-based (BBD) or corn-based diets (CBD), or their equal blend (BCBD) on dry matter (DM) intake, feeding and chewing behavior, and production performance of lactating dairy cows was evaluated. Nine multiparous Holstein cows (75.6 ± 11.0 d in milk) were used in a triplicate 3 × 3 Latin square design with 21-d periods. Forage-to-concentrate ratio (40:60), forage neutral detergent fiber (20% of DM), total neutral detergent fiber (>29% of DM), and geometric mean particle size (4.3mm) were similar among treatments. Meal patterns, including meal size and intermeal interval, were not affected by the dietary treatments and DM intake (25.6 kg/d) was not different among treatments. Ether extract intake increased linearly with increasing amount of the corn grain in the diets. Due to similar feed intake, actual milk (48.6 kg/d), 4% fat-corrected milk (36.8 kg/d), and fat- and protein-corrected milk (38.1 kg/d) yields were not affected by treatments. Average milk protein percentage and yield were 2.83% and 1.37 kg/d, respectively, and were not different across treatments. Milk fat percentage increased linearly with increasing amount of corn grain in the diets and was greater in CBD relative to BCBD but not BBD (2.31, 2.28, and 2.57%, for BBD, BCBD, and CBD, respectively). However, milk fat yield tended to show a linear increase as the amount of corn grain included in the diets increased. Results indicated that changing diet fermentability by replacing barley grain for corn grain in oil-supplemented diets did not influence feeding patterns and thereby no changes in feed intake and milk yield occurred. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Dietary variety is associated with larger meals in female rhesus monkeys.

    PubMed

    Moore, Carla J; Michopoulos, Vasiliki; Johnson, Zachary P; Toufexis, Donna; Wilson, Mark E

    2013-07-02

    The complex, interacting influences on eating behavior and energy expenditure prevent elucidation of the causal role of any single factor in the current obesity epidemic. However, greater variety in the food supply, particularly in the form of highly palatable, energy-dense foods, has likely made a contribution. This study was undertaken to test the hypothesis that greater dietary variety is associated with greater caloric intake within individual meals consumed by free-feeding, socially-housed female rhesus monkeys. Meal patterns were assessed during two, two-week dietary phases. One phase consisted of a choice between a standard chow diet and a highly palatable diet (HPD). The other phase consisted of access to the chow only. Food intake for each subject was recorded continuously using previously validated, automated feeders, and a meal was defined based on a minimum kilocalorie requirement and a minimum inter-meal interval. During the choice condition, animals electively consumed mixed meals that incorporated both diets as well as other meals that consisted exclusively of a single diet - chow-only or HPD-only. Animals consumed the most calories per meal when the meal was comprised of both the chow and HPD, which differed in caloric density, flavor, and texture. Interestingly, however, there was no significant difference in the amount of calories consumed as HPD-only meals in the choice condition compared to meals in the chow-only, no choice condition, suggesting consumption of a single food during a meal, regardless of palatability, provides a constant sensory experience that may lead to more rapid habituation and subsequent meal cessation. Additionally, during the dietary choice condition, animals consumed fewer calories in the form of chow-only meals. Thus, the present results suggest that limiting dietary variety, regardless of palatability, may be a useful strategy for weight loss in overweight and obese individuals by reducing caloric intake within individual meals. © 2013.

  17. Dietary obesity caused by a specific circadian eating pattern.

    PubMed

    Hariri, Niloofar; Thibault, Louise

    2011-04-01

    The eating pattern is altered by high-fat diet-induced obesity. To clarify whether this is dependent on the fatty acid profile of the diet, the authors conducted two studies on adult female Sprague-Dawley rats fed normal-fat chow or high-fat diets with varying fatty acid composition. Eating pattern and body weight were assessed in rats fed canola-based (low in saturated fatty acids) or lard-based (moderate in saturated fatty acids) diets for 7 days, and in animals fed chow or canola- or butter-based diets (rich in saturated fatty acids) for 43 days. These parameters were also determined when restricted amounts of low-fat canola- or butter-based diets were consumed for 25 days. Early exposure to canola or lard high-fat feeding or prolonged access to canola- or butter-based fat-rich diets (relative to chow feeding) did not alter the normal light-dark distribution of food and energy intake. All animals ingested most of their food during the dark phase. However, feeding the high-fat canola- and butter-based diets produced an altered eating pattern during the light phase characterized by a smaller number of meals, longer intermeal interval, and enhanced satiety ratio, and consumption of shorter-lasting meals than chow-fed animals. Relative to canola or chow feeding, butter-fed animals consumed a lower number of meals during the dark phase and had a higher eating rate in the light phase, but ate larger meals overall. Only butter feeding led to overeating and obesity. When given a restricted amount of low-fat canola- or butter-based diet at the start of the light phase, rats ate most of their food in that phase and diurnal rather than nocturnal feeding occurred with restriction. These findings underscore the role of saturated fatty acids and the resulting eating pattern alteration in the development of obesity.

  18. Ups and downs of a transcriptional landscape shape iron deficiency associated chlorosis of the maize inbreds B73 and Mo17

    PubMed Central

    2013-01-01

    Background Improving nutrient homeostasis is a major challenge of a sustainable maize cultivation, and cornerstone to ensure food supply for a growing world population. Although, iron constitutes an important nutrient, iron availability is limited. In this respect, iron deficiency associated chlorosis causes severe yield losses every year. Natural variation of the latter trait has yet not been addressed in maize and was therefore studied in the present analysis. Results In this study, we i) report about the contrasting chlorosis phenotypes of the inbreds B73 and Mo17 at 10 and 300 μM iron regime, ii) identified over 400 significantly regulated transcripts (FDR < 0.05) within both inbreds at these growth conditions by deep RNA-Sequencing, iii) linked the gained knowledge with QTL information about iron deficiency related traits within the maize intermated B73 by Mo17 (IBM) population, and iv) highlighted contributing molecular pathways. In this respect, several genes within methionine salvage pathway and phytosiderophore synthesis were found to present constitutively high expression in Mo17, even under sufficient iron supply. Moreover, the same expression pattern could be observed for two putative bHLH transcription factors. In addition, a number of differentially expressed genes showed a co-localisation with QTL confidence intervals for iron deficiency related traits within the IBM population. Conclusions Our study highlights differential iron deficiency associated chlorosis between B73 and Mo17 and represents a valuable resource for differentially expressed genes upon iron limitation and chlorosis response. Besides identifying two putative bHLH transcription factors, we propose that methionine salvage pathway and sterol metabolism amongst others; underlie the contrasting iron deficiency related chlorosis phenotype of both inbreds. Altogether, this study emphasizes a contribution of selected genes and pathways on natural trait variation within the IBM population. PMID:24330725

  19. Efficacy of a computerized system applied to central operating theatre for medical records collection.

    PubMed

    Yamamoto, K; Ogura, H; Furutani, H; Kitazoe, Y; Takeda, Y; Hirakawa, M

    1986-01-01

    A computer system operation is introduced, which has been in use since October 1981 at Kochi medical school as one of the integral sub-systems of the total hospital information system called IMIS. The system was designed from the beginning with the main purposes of obtaining better management of operations, and detailed medical records are included for before, during and after operations. It is shown that almost all operations except emergencies were managed using the computer system rather than the paper system. After presenting some of the results of the accumulated records we will discuss the reason for this high frequency of use of the computer system.

  20. Bank Powers. Activities of Securities, Subsidiaries of Bank Holding Companies

    DTIC Science & Technology

    1990-03-01

    AD-A281 232 -A’’ N4 ,~ 2’**~VN 94-20700 ¶~ JW’"I t A~ ImI 94 7- J -7.,? DI CLIMER OTI-C THIS DOCUMENT IS BEST QUALITY.AVAILABLB. THE COPY FURNISHED...terms of market share changes, the piricing of scurities. and benefits to the consumer: and how the 1H3rd’- K.ik ,\\.t ’ .I,,, j m’d 1-.1t4 .4sl,., IMha...of bank-i~iw and sectiritie~sactivities as is mandated in the U’nited State&. In these ".,u ;( j "-:ST.faiiiIrn ൖH N. paig.- 2anud3: Paeg I I GAO

  1. Factors influencing the production of cellulase by Aspergillus fumigatus (Fresenius).

    PubMed

    Stewart, J C; Parry, J B

    1981-07-01

    During growth in liquid culture containing a single cellulosic or non-cellulosic carbon source, a newly isolated strain of Aspergillus fumigatus released cellulases into the medium; the amounts produced depended on the nitrogen source, the type and concentration of the carbon source, pH and temperature. Extracellular cellulolytic activity was still increasing after incubation for 60 d with 1% (W/V) CF11 cellulose, (NH4)2SO4 as nitrogen source and a starting pH of 7. The activities of the new isolate were compared with those of A. fumigatus IMI 143864 and Trichoderma reesei QM6a (ATCC 13631) and it was shown to be a good producer of beta-glucosidase.

  2. Collaborative medical informatics research using the Internet and the World Wide Web.

    PubMed Central

    Shortliffe, E. H.; Barnett, G. O.; Cimino, J. J.; Greenes, R. A.; Huff, S. M.; Patel, V. L.

    1996-01-01

    The InterMed Collaboratory is an interdisciplinary project involving six participating medical institutions. There are two broad mandates for the effort. The first is to further the development, sharing, and demonstration of numerous software and system components, data sets, procedures and tools that will facilitate the collaborations and support the application goals of these projects. The second is to provide a distributed suite of clinical applications, guidelines, and knowledge-bases for clinical, educational, and administrative purposes. To define the interactions among the components, datasets, procedures, and tools that we are producing and sharing, we have identified a model composed of seven tiers, each of which supports the levels above it. In this paper we briefly describe those tiers and the nature of the collaborative process with which we have experimented. PMID:8947641

  3. Impact of intramammary tilmicosin infusion as a dry cow therapy.

    PubMed

    Mohammadsadegh, M

    2018-02-01

    Three hundred subclinically infected quarters of 259 Holstein cows infected with gram-positive bacteria were selected via quota sampling based on the California Mastitis Test (CMT) result and were divided randomly and equally into treatment and test groups. Quarters of test group (n = 150 in 128 cows) were treated with an intramammary infusion of tilmicosin, and quarters of the control group (n = 150 in 131 cows) were treated with cloxacillin as a traditional intramammary infusion of dry cow (DC) ointment. Cows with more than one infected quarter were randomly assigned to the same group, and adjacent quarters were treated the same. The milk samples of all quarters were obtained, and bacterial cultures and somatic cell count (SCC) were tested before dry cow therapy (DCT) (50 ± 15 days before parturition), and finally on day 2 of the next lactation. Results have shown that total bacteriological cure rates on day 2 of the next lactation were 45% and 78%, (p = .01), new infection rates were 43.3% and 56.6%, and SCC was (6.732 × 10 5  ± 3.124 × 10 5 ) and (5.025 × 10 5  ± 2.935 × 10 5 ), (p > .05) in test and control groups, respectively. Tilmicosin had less effect on reducing IMI due to Corynebacterium bovis, and had no effect on Streptococcus agalactiae, but had a potent effect against Staphylococcus aureus. It was concluded that tilmicosin alone should not be infused as an alternative to conventional dry cow therapy. However, it had a significant effect against S. aureus, and the potential of tilmicosin to treat S. aureus IMI should be confirmed in further studies. © 2017 John Wiley & Sons Ltd.

  4. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study reveals virulence factors and phenotypic characteristics of MPEC that may play a role in pathogenesis of E. coli mastitis. PMID:26327312

  5. Imipenem heteroresistance in nontypeable Haemophilus influenzae is linked to a combination of altered PBP3, slow drug influx and direct efflux regulation.

    PubMed

    Cherkaoui, A; Diene, S M; Renzoni, A; Emonet, S; Renzi, G; François, P; Schrenzel, J

    2017-02-01

    To investigate the potential roles of PBPs, efflux pumps and slow drug influx for imipenem heteroresistance in nontypeable Haemophilus influenzae (NTHi). Fifty-nine NTHi clinical isolates examined in this study were collected at Geneva University Hospitals between 2009 and 2014. Alterations in PBPs were investigated by gene sequencing. To evaluate the affinities of the PBPs to imipenem, steady-state concentration-response experiments were carried out using imipenem in a competition assay with Bocillin-FL. The effect of the carbonyl cyanide m-chlorophenylhydrazone (CCCP) on imipenem susceptibility was assessed using broth dilution and viable cell counting. Using whole-genome sequencing, we explored the potential roles of outer membrane protein P2 (OmpP2), LytM proteins and the dcw gene cluster in imipenem heteroresistance. All 46 imipenem-heteroresistant isolates (IMI hR ) harboured amino acid substitutions in the ftsI gene, which encodes PBP3, corresponding to 25 different mutation patterns that varied from the ftsI gene mutation patterns found in imipenem-susceptible isolates. Among all PBPs, the highest affinity to imipenem was documented for PBP3 (IC 50 , 0.004 μg/mL). Different amino acid substitutions and insertions were noted in OmpP2, suggesting a relationship with imipenem heteroresistance. The IMI hR isolates were affected by CCCP differently and displayed a higher percentage of killing by imipenem in CCCP-treated cells at concentrations ranging between 0.5 and 8 μg/mL. The present study provides robust evidence indicating that in combination with the altered PBP3, the slowed drug influx and its enhanced efflux due to the loss of regulation led to the development of imipenem heteroresistance in NTHi. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

    PubMed

    Tzogani, Kyriaki; van Hennik, Paula; Walsh, Ita; De Graeff, Pieter; Folin, Annika; Sjöberg, Jan; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

    2018-05-01

    On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. The recommended starting dose of panobinostat is 20 mg, taken orally in a cyclical manner for up to 48 weeks.The use of panobinostat in combination with bortezomib and dexamethasone was studied in a randomized, double-blind, placebo-controlled, multicenter phase III study (PANORAMA I) in 768 patients with relapsed or relapsed and refractory multiple myeloma who had received one to three prior lines of therapies. In the subgroup of patients who have received at least two prior regimens including bortezomib and an IMiD, there was a difference of 7.8 months in the progression-free survival in favor of the experimental arm (12.5 months for panobinostat + bortezomib + dexamethasone vs. 4.7 months for placebo + bortezomib + dexamethasone; hazard ratio = 0.47, 95% confidence interal 0.31-0.72; log-rank p value = .0003). The incidence of grade 3-4 adverse events suspected to be related to study drug was 76.9% vs. 51.2%, for the panobinostat and the placebo group, respectively. The most common side effects (grade 3-4) associated with panobinostat included diarrhea (18.9%), fatigue (14.7%), nausea (4.5%), vomiting (5.5%), thrombocytopenia (43.6%), anemia (7.9%), neutropenia (16.5%) and lymphopenia (8.1%).This article summarizes the scientific review of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landing_page.jsp&mid=). Farydak was approved in the European Union in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD). The addition of panobinostat to bortezomib and dexamethasone resulted in a clinically meaningful and statistically significant improvement of progression-free survival compared with bortezomib and dexamethasone, and an additional therapeutic option with a new mechanism of action was considered valuable. Although the toxicity associated with panobinostat combination was significant, at the time of the marketing authorization of panobinostat, it was considered that it was acceptable and that it should be left to the clinician and the patient to decide whether the panobinostat combination is the preferred treatment option or not. © AlphaMed Press 2017.

  7. New coumarin derivatives: design, synthesis and use as inhibitors of hMAO.

    PubMed

    He, Xu; Chen, Yan-Yan; Shi, Jing-Bo; Tang, Wen-Jiang; Pan, Zhi-Xiang; Dong, Zhi-Qiang; Song, Bao-An; Li, Jun; Liu, Xin-Hua

    2014-07-15

    A series new 2H-chromene-3-carboxamides (4a-4i) and S-2H-chromene-3-carbothioates (5j-5t) were synthesized and evaluated as monoamine oxidase A and B inhibitors. Among them, compound 5k (IC50=0.21μM, IC50 iproniazid=7.65μM) showed the most activity and higher MAO-B selectivity (189.2-fold vs 1-fold) with respect to the MAO-A isoform. The need to clarify at a 3D level some important molecular aspects of discussed SAR, we undertaked a number of docking simulations to better assess. The steric effect was analyzed interms of both posing and scoring by investigating the nature of the binding interactions. The docking results of active compound 5k with hMAO-B complex indicated that conserved residue ILE 199 was important for ligand binding via Sigma-Pi interaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Learning Methodology for Early Child Education Education (Paud) in the Recognition of Legal Capitals based on Android

    NASA Astrophysics Data System (ADS)

    Siswanto, Didik

    2017-12-01

    School as a place to study require a medium of learning. Instructional media containinginformation about the lessons that will be used by teachers to convey a lesson. School early childhood education Al-Kindy Pekanbaru interms of learning the letter hijaiyah still use conventional learning media. But with the conventionalmedia is not very attractive to use, so the need for an exciting learning medium that can make childrenbecome interested in learningThe purpose of this study was to create a Media Learning Introduction Letter Hijaiyahmultimedia form and benefit from the introduction of letters Hijaiyah Learning Media is a renewal of themedium of learning in School early childhood education Al-Kindy Pekanbaru.In this study the authors tried to make the learning application that contains the basicknowledge of letters hijaiyah dsertai with animation, audio and explanation how to read the letters inorder to complete the learning media letters hijaiyah more interactive.

  9. Quantitative analysis of interfacial chemistry in TiC/Ti composite using electron-energy-loss spectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gu, M.; Jiang, W.; Zhang, G.

    Due to titanium carbide`s physical and elastic properties, titanium carbide particles are widely used as a reinforcement in titanium-alloy-based composites. Previous studies have shown that no obvious reaction products were detected on the interface region in TiC/Ti alloy systems; instead, a nonstoichiometric region in the TiC particle between the Ti{sub 6}Al{sub 4}V alloy and the stoichiometric TiC was found. However, the nature and the extent of the nonstoichiometric zone have not been quantitatively described. The present communication reports some results of a parallel electron-energy-loss spectroscopy (PEELS) study on a 10 vol pct TiC-particle-reinforced IMI-829 metal-matrix composite.

  10. Endo Atmospheric-Exo Atmospheric Radar Modeling. Volume II. Part I. Computer Program Documentation.

    DTIC Science & Technology

    1976-06-01

    oil , i L L i tN v Mr I I I IMI I ANTAZ 0,t ANiF Lu ;, L bST It L, -’T...k ALJ kt/PALTIM 1,46 GUTUTU1501 I’L It LUV K-.JNTTL ;2ui ibut T L14TVr.L 1, .L,’Lt 1 111i;l, AUTLILCW LhAKI SL - -WL/SLL RADSIM LA,, N’,. t I Nill - I ...AtNL I (b~N( ’C, -el * II’E13 ). NSF I . tt(ILOI. jF.y(AI 1-1At*1./ ’ It I I vi;, L,. 0 LI Luv o9 k LI t ( MLL t I !L . 1LA t. ’LIt It (NSUov

  11. Mastitis of periparturient Holstein cattle: a phenotypic and genetic study.

    PubMed

    Detilleux, J C; Kehrli, M E; Freeman, A E; Fox, L K; Kelley, D H

    1995-10-01

    Environmental and genetic factors affecting somatic cell scores, clinical mastitis, and IMI by minor and major pathogens were studied on 137 periparturient Holstein cows selected for milk production. Environmental effects were obtained by generalized least squares and logistic regression. Genetic parameters were from BLUP and threshold animal models. Lactation number affected the number of quarters with clinical mastitis and the number of quarters infected with minor pathogens. The DIM affected somatic cell score and number of quarters infected with major pathogens. Heritabilities for all mastitis indicators averaged 10%, but differences occurred among the indicators. Correlations between breeding values of the number of quarters infected with minor pathogens and the number infected with major pathogens were antagonistic and statistically significant.

  12. Insuffisance cervicale et cerclage cervical.

    PubMed

    Brown, Richard; Gagnon, Robert; Delisle, Marie-France

    2016-12-01

    La présente directive clinique a pour but de fournir un cadre de référence que les cliniciens pourront utiliser pour identifier les femmes qui sont exposées aux plus grands risques de connaître une insuffisance cervicale, ainsi que pour déterminer les circonstances en présence desquelles la mise en place d'un cerclage pourrait s'avérer souhaitable. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en 2012 au moyen d'un vocabulaire contrôlé (p. ex. « uterine cervical incompetence ») et de mots clés appropriés (p. ex. « cervical insufficiency », « cerclage », « Shirodkar », « cerclage », « MacDonald », « cerclage », « abdominal », « cervical length », « mid-trimester pregnancy loss »). Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n'a été appliquée en matière de date ou de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en janvier 2011. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). RECOMMANDATIONS. Copyright © 2016. Published by Elsevier Inc.

  13. Intrinsic mechanical properties and strengthening methods in inorganic crystalline materials

    NASA Astrophysics Data System (ADS)

    Mecking, H.; Hartig, Ch.; Seeger, J.

    1991-06-01

    The paper deals with strength and fracture in metals, ceramics and intermetallic compounds. The emphasis is on the interrelation between microstructure and macroscopic behavior and how the concepts for alloy design are mirroring this interrelationship. The three materials classes are distinguished by the physical nature of the atomic bonding forces. In metals metallic bonding predominates which causes high ductility but poor strength. Accordingly material development concentrates on production of microstructures which optimize the yield strength without unacceptable loss in ductility. In ceramics covalent bonding prevails which results in high hardness and high elastic stiffness but at the same time extreme brittleness. Contrary to the metal-ease material development aims at a kind of pseudo ductility in order to rise the fracture toughness to sufficiently high levels. In intermetallic phases the atomic bonds are a mixture of metallic and covalent bonding where depending on the alloying system the balance between the two contributions may be quite different. Accordingly the properties of intermetallics are in the range between metals and ceramics. By a variety of microstructural measures their properties can be changed in direction. either towards metallic or ceramic behavior. General rules for alloy design are not available, rather every system demands very specific experience since properties depend to a considerable part on intrinsic properties of lattice defects such as dislocations, antiphase boundaries, stacking faults and grain boundaries. Cet article traite de la résistance et de la fracture des métaux, des céramiques et des composés intermétalliques. L'accent est mis sur les correspondances entre la microstructure et le comportement macroscopique ainsi que sur la façon dont de tels concepts se reflètent dans la création de nouveaux alliages. C'est la nature des forces de liaisons qui distingue chaque type de matériaux. Dans les métaux, les liaisons métalliques dominent, ce qui entraîne une grande ductilité mais une médiocre résistance. En conséquence, dans le développement de nouveaux matériaux on cherche préférentiellement à produire des microstructures qui optimisent la résistance élastique sans perte inacceptable de ductilité. Dans les céramiques, les liaisons covalentes prédominent; ceci entraîne une dureté élevée, une grande rigidité, mais en même temps une extrême fragilité. Au contraire des métaux, le développement de ces matériaux vise à obtenir une pseudoductilité afin d'amener la tenacité à des niveaux suffisamment élevés. Dans les phases intermétalliques les liaisons atomiques correspondent à un mélange de liaisons métalliques et covalentes. La contribution de chacune d'entre elles varie en fonction du système allié. En conséquence, les propriétés des intermétalliques se situent entre celles des métaux et des céramiques. Par divers changements microstructuraux des propriétés peuvent être déplacées pour se rapprocher d'un comportement de type métallique ou de type céramique. Donner des règles générales pour la création de nouveaux alliages n'est pas possible car chaque système demande à être testé, les propriétés dépendent en effet, pour une part considérable, des propriétés intrinsèques des défauts de réseau comme les dislocations, les parois d'antiphase ou les joints de grains.

  14. Marine Environmental Planning Guide for the Hampton Roads/Norfolk Operating Area.

    DTIC Science & Technology

    1974-05-01

    t~J ’SWo 10 𔃻 ..... 43303UA~ A** 00 * 1 31.9 -~f -- f., 41 Aef"G .G 3 3 -1.9’ OC ’amV. -.9v ... G "* Cft 𔃻 IAMv PPO.$ ENLARGEMENT E o Iy PERMISSION...ut DlAl’ aml I indane on qlycolyt ic andi ,J I L1 ’ 11 n<K~~ Ionic (!i~~sot thec 4pahi,; , Me rcxvn aria mercenavr-ia, 5- ,7p., Uiuted Nit tons PuxA...North Cairol imi Dtpt . ot (Con.;etVat ion .iml DlX’,󈧏Tnt , Divi!;ion oit Cimmrcixil ’~~~~I~ by .B.li;t IuX inll sst~b illa5𔃿 i Strulctlure aml

  15. Occurrence of free and conjugated 12,13-epoxytrichothecenes and zearalenone in banana fruits infected with Fusarium moniliforme.

    PubMed Central

    Chakrabarti, D K; Ghosal, S

    1986-01-01

    Three recognized 12,13-epoxytrichothecene mycotoxins, trichothecolone, diacetoxyscirpenol, and T-2 toxin, and a hyperestrogenic factor, zearalenone, together with the fatty acid esters of trichothecolone, scirpenetriol, T-2 tetraol, and zearalenone, were isolated from the flask culture extractives of Fusarium moniliforme Sheldon (IMI 225232) as well as from the fruit of banana (Musa sapientum L.) infected with the same fungus in the field and in storage. The total concentrations of these toxins in the naturally infected fruits were quite high (0.8 to 1.0 mg/g of fruit). F. moniliforme infections of banana fruits, being of wide occurrence in the world, could cause serious health problems in humans when the infected fruits are ingested for a prolonged period of time. Images PMID:2937364

  16. U-BIOPRED: evaluation of the value of a public-private partnership to industry.

    PubMed

    Riley, John H; Erpenbeck, Veit J; Matthews, J G; Holweg, C T J; Compton, C; Seibold, W; Higenbottam, T; Wagers, S S; Rowe, A; Myles, D

    2018-06-21

    Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) was initiated in the first year of the Innovative Medicines Initiative (IMI). It was an ambitious plan to tackle the understanding of asthma through an integration of clinical and multi-'omics approaches that necessitated the bringing together of industry, academic, and patient representatives because it was too large to be managed by any one of the partners in isolation. It was a novel experience for all concerned. In this review, we describe the main features of the U-BIOPRED experience from the industry perspective. We list some of the key advantages and learnings from the perspective of the authors, and also improvements that we feel could be made in future projects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Investigation of Behaviorally Modified Rats for Use in Explosives Detection Systems

    DTIC Science & Technology

    1981-12-01

    c. 4o t W iet s mi4w dltr’elm-jueiealolf- ltii*liti . .t.wnu sit - ass e-nz Iati ifovit l iutr in jIrrf-rt-F1wr to. thr lkillin aitinal. il if" O.W.tf...8217joizzle iwo%𔃾 ill .,rdtr . d1a44, tit" alsa Ilsr"’I (olf..~ .4144 if i Ow .1fi4j4.Iiumi.4-l4p sit Iii- t.’ l m~I14r.414r1 d4 atiim l-. leo *.rt1.-r is...urvisisi-. I Ifi- -1its 1%a- 1.11, -esi f, rf a 1 -Illijvvt. li-es ill [ies 1 irtlit- wyit eirmr ilist-- sit . ii- IsrpIllssLitinitijl 1Imi-iid

  18. UV-photodegradation of desipramine: Impact of concentration, pH and temperature on formation of products including their biodegradability and toxicity.

    PubMed

    Khaleel, Nareman D H; Mahmoud, Waleed M M; Olsson, Oliver; Kümmerer, Klaus

    2016-10-01

    Desipramine (DMI) is a widely used tricyclic antidepressant, and it is the major metabolite of imipramine (IMI) and lofepramine (LMI); IMI and LMI are two of the most commonly used tricyclic antidepressants. If DMI enters the aquatic environment, it can be transformed by the environmental bacteria or UV radiation. Therefore, photolysis of DMI in water was performed using a simulated sunlight Xenon-lamp and a UV-lamp. Subsequently, the biodegradability of DMI and its photo-transformation products (PTPs) formed during its UV photolysis was studied. The influence of variable conditions, such as initial DMI concentration, solution pH, and temperature, on DMI UV photolysis behavior was also studied. The degree of mineralization of DMI and its PTPs was monitored. A Shimadzu HPLC-UV apparatus was used to follow the kinetic profile of DMI during UV-irradiation; after that, ion-trap and high-resolution mass spectrometry coupled with chromatography were used to monitor and identify the possible PTPs. The environmentally relevant properties and selected toxicity properties of DMI and the non-biodegradable PTPs were predicted using different QSAR models. DMI underwent UV photolysis with first-order kinetics. Quantum yields were very low. DOC values indicated that DMI formed new PTPs and was not completely mineralized. Analysis by means of high-resolution mass spectrometry revealed that the photolysis of DMI followed three main photolysis pathways: isomerization, hydroxylation, and ring opening. The photolysis rate was inversely proportional to initial DMI concentration. The pH showed a significant impact on the photolysis rate of DMI, and on the PTPs in terms of both formation kinetics and mechanisms. Although temperature was expected to increase the photolysis rate, it showed a non-significant impact in this study. Results from biodegradation tests and QSAR analysis revealed that DMI and its PTPs are not readily biodegradable and that some PTPs may be human and/or eco-toxic, so they may pose a risk to the environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Comparative analysis of miRNAs of two rapeseed genotypes in response to acetohydroxyacid synthase-inhibiting herbicides by high-throughput sequencing.

    PubMed

    Hu, Maolong; Pu, Huiming; Gao, Jianqin; Long, Weihua; Chen, Feng; Zhang, Wei; Zhou, Xiaoyin; Peng, Qi; Chen, Song; Zhang, Jiefu

    2017-01-01

    Acetohydroxyacid synthase (AHAS), also called acetolactate synthase, is a key enzyme involved in the first step of the biosynthesis of the branched-chain amino acids valine, isoleucine and leucine. Acetohydroxyacid synthase-inhibiting herbicides (AHAS herbicides) are five chemical families of herbicides that inhibit AHAS enzymes, including imidazolinones (IMI), sulfonylureas (SU), pyrimidinylthiobenzoates, triazolinones and triazolopyrimidines. Five AHAS genes have been identified in rapeseed, but little information is available regarding the role of miRNAs in response to AHAS herbicides. In this study, an AHAS herbicides tolerant genotype and a sensitive genotype were used for miRNA comparative analysis. A total of 20 small RNA libraries were obtained of these two genotypes at three time points (0h, 24 h and 48 h) after spraying SU and IMI herbicides with two replicates. We identified 940 conserved miRNAs and 1515 novel candidate miRNAs in Brassica napus using high-throughput sequencing methods combined with computing analysis. A total of 3284 genes were predicted to be targets of these miRNAs, and their functions were shown using GO, KOG and KEGG annotations. The differentiation expression results of miRNAs showed almost twice as many differentiated miRNAs were found in tolerant genotype M342 (309 miRNAs) after SU herbicide application than in sensitive genotype N131 (164 miRNAs). In additiond 177 and 296 miRNAs defined as differentiated in sensitive genotype and tolerant genotype in response to SU herbicides. The miR398 family was observed to be associated with AHAS herbicide tolerance because their expression increased in the tolerant genotype but decreased in the sensitive genotype. Moreover, 50 novel miRNAs from 39 precursors were predicted. There were 8 conserved miRNAs, 4 novel miRNAs and 3 target genes were validated by quantitative real-time PCR experiment. This study not only provides novel insights into the miRNA content of AHAS herbicides tolerant rapeseed in response to AHAS herbicides, but also demonstrates that miRNAs may be involved in AHAS herbicides tolerance.

  20. Comparative analysis of miRNAs of two rapeseed genotypes in response to acetohydroxyacid synthase-inhibiting herbicides by high-throughput sequencing

    PubMed Central

    Hu, Maolong; Pu, Huiming; Gao, Jianqin; Long, Weihua; Chen, Feng; Zhang, Wei; Zhou, Xiaoyin; Peng, Qi; Chen, Song; Zhang, Jiefu

    2017-01-01

    Acetohydroxyacid synthase (AHAS), also called acetolactate synthase, is a key enzyme involved in the first step of the biosynthesis of the branched-chain amino acids valine, isoleucine and leucine. Acetohydroxyacid synthase-inhibiting herbicides (AHAS herbicides) are five chemical families of herbicides that inhibit AHAS enzymes, including imidazolinones (IMI), sulfonylureas (SU), pyrimidinylthiobenzoates, triazolinones and triazolopyrimidines. Five AHAS genes have been identified in rapeseed, but little information is available regarding the role of miRNAs in response to AHAS herbicides. In this study, an AHAS herbicides tolerant genotype and a sensitive genotype were used for miRNA comparative analysis. A total of 20 small RNA libraries were obtained of these two genotypes at three time points (0h, 24 h and 48 h) after spraying SU and IMI herbicides with two replicates. We identified 940 conserved miRNAs and 1515 novel candidate miRNAs in Brassica napus using high-throughput sequencing methods combined with computing analysis. A total of 3284 genes were predicted to be targets of these miRNAs, and their functions were shown using GO, KOG and KEGG annotations. The differentiation expression results of miRNAs showed almost twice as many differentiated miRNAs were found in tolerant genotype M342 (309 miRNAs) after SU herbicide application than in sensitive genotype N131 (164 miRNAs). In additiond 177 and 296 miRNAs defined as differentiated in sensitive genotype and tolerant genotype in response to SU herbicides. The miR398 family was observed to be associated with AHAS herbicide tolerance because their expression increased in the tolerant genotype but decreased in the sensitive genotype. Moreover, 50 novel miRNAs from 39 precursors were predicted. There were 8 conserved miRNAs, 4 novel miRNAs and 3 target genes were validated by quantitative real-time PCR experiment. This study not only provides novel insights into the miRNA content of AHAS herbicides tolerant rapeseed in response to AHAS herbicides, but also demonstrates that miRNAs may be involved in AHAS herbicides tolerance. PMID:28950015

  1. A Network Meta-Analysis of the Relative Efficacy of Treatments for Actinic Keratosis of the Face or Scalp in Europe

    PubMed Central

    Vegter, Stefan; Tolley, Keith

    2014-01-01

    Background Several treatments are available for actinic keratosis (AK) on the face and scalp. Most treatment modalities were compared to placebo and therefore little is known on their relative efficacy. Objectives To compare the different treatments for mild to moderate AK on the face and scalp available in clinical practice in Europe. Methods A network meta-analysis (NMA) was performed on the outcome “complete patient clearance”. Ten treatment modalities were included: two 5-aminolaevulinic acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch; methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a 2–3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5% hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only data available for 5% 5-FU was from one small study and was determined to be too limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data from illumination with narrow-band lights were selected as these are typically used in clinical practice. The NMA was performed with a random-effects Bayesian model. Results 25 trials on 5,562 patients were included in the NMA. All active treatments were significantly better than placebo. BF-200 ALA showed the highest efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had the highest probability to be the best treatment and the highest SUCRA score (64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5% (7.2% and 66.8%). Conclusions This NMA showed that BF-200 ALA, using narrow-band lights, was the most efficacious treatment for mild to moderate AK on the face and scalp. This analysis is relevant for clinical decision making and health technology assessment, assisting the improved management of AK. PMID:24892649

  2. Ka`Imi`Ike: Explorations in the Geosciences from an Indigenous Perspective

    NASA Astrophysics Data System (ADS)

    Gibson, B. A.; Puniwai, N.; Sing, D.; Ziegler-Chong, S.

    2006-12-01

    The Ka `Imi `Ike Program is a recent initiative at the University of Hawai`i whose mission is to recruit and retain Native Hawaiian and Pacific Islanders (NHPI) to disciplines within the geosciences. The Program seeks to create pathways for NHPI students interested in geoscience disciplines through various venues and activities, including linking science with culture and community through a summer boarding experience for incoming freshman or sophomore University of Hawaii students. The 3-week institute, Explorations in Geosciences, was offered for the first time in Summer 2006. The 10 college students who participated were introduced to mentor geoscientists to learn more about the different disciplines and the pathways the scientists took in their careers. Hands-on activities trained students in current technology (such as GPS) and exposed them to how the technology was used in different research applications. A key and crucial component of the Explorations in Geosciences summer program was that "local" or Native Hawaiian role models were selected as the geoscience mentors whenever possible and mostly local and regional examples of geoscience phenomena were used. Moreover, the "science" learned throughout the summer program was linked to local Traditional Environmental Knowledge (TEK) by a Native Hawaiian kumu (teacher). The merging of "western" science with traditional knowledge reinforced geoscience concepts, and afforded the students an opportunity to better understand how a career in the geosciences could be beneficial to them and their community. At the end of the summer institute, the students had to give a final presentation of what geoscience concepts and careers they thought were most interesting to them, and how the program impacted their view of the geosciences. They also had to keep a daily journal which outlined their thoughts about the topics presented each day of the summer institute. Preliminary assessment reveals that several of the students came away from the summer program with a better understanding of the geosciences and are now considering a possible career in a geoscience discipline. The students also indicated that the linking of traditional knowledge with "western" science strengthened their perception of how the geosciences are a part of their cultural understanding of the environmental.

  3. Design strategies to improve patient motivation during robot-aided rehabilitation.

    PubMed

    Colombo, Roberto; Pisano, Fabrizio; Mazzone, Alessandra; Delconte, Carmen; Micera, Silvestro; Carrozza, M Chiara; Dario, Paolo; Minuco, Giuseppe

    2007-02-19

    Motivation is an important factor in rehabilitation and frequently used as a determinant of rehabilitation outcome. Several factors can influence patient motivation and so improve exercise adherence. This paper presents the design of two robot devices for use in the rehabilitation of upper limb movements, that can motivate patients during the execution of the assigned motor tasks by enhancing the gaming aspects of rehabilitation. In addition, a regular review of the obtained performance can reinforce in patients' minds the importance of exercising and encourage them to continue, so improving their motivation and consequently adherence to the program. In view of this, we also developed an evaluation metric that could characterize the rate of improvement and quantify the changes in the obtained performance. Two groups (G1, n = 8 and G2, n = 12) of patients with chronic stroke were enrolled in a 3-week rehabilitation program including standard physical therapy (45 min. daily) plus treatment by means of robot devices (40 min., twice daily) respectively for wrist (G1) and elbow-shoulder movements (G2). Both groups were evaluated by means of standard clinical assessment scales and the new robot measured evaluation metric. Patients' motivation was assessed in 9/12 G2 patients by means of the Intrinsic Motivation Inventory (IMI) questionnaire. Both groups reduced their motor deficit and showed a significant improvement in clinical scales and the robot measured parameters. The IMI assessed in G2 patients showed high scores for interest, usefulness and importance subscales and low values for tension and pain subscales. Thanks to the design features of the two robot devices the therapist could easily adapt training to the individual by selecting different difficulty levels of the motor task tailored to each patient's disability. The gaming aspects incorporated in the two rehabilitation robots helped maintain patients' interest high during execution of the assigned tasks by providing feedback on performance. The evaluation metric gave a precise measure of patients' performance and thus provides a tool to help therapists promote patient motivation and hence adherence to the training program.

  4. Association of self-reported sleep duration with eating behaviors of American adults: NHANES 2005–20101234

    PubMed Central

    Graubard, Barry I

    2014-01-01

    Background: Published evidence suggests an inverse association between sleep duration and body weight status. Objective: We examined the association of sleep duration with eating behaviors reported by adult Americans to understand the relation between sleep duration and body weight status. Design: This cross-sectional study used sleep duration and dietary data from the continuous NHANES conducted from 2005 to 2010 (n = 15,199, age ≥20 y). Eating behaviors examined included the following: reporting of and energy from main meals (breakfast, lunch, and dinner) and snacks (before breakfast, after dinner, and after 2000 h), intermeal intervals, time of day of main meal reporting, and intakes of macronutrients and beverages. Multiple regression methods were used to examine the independent association of hours of sleep duration grouped as short (≤6 h), average (7–8 h), and long (≥9 h) with eating behavior outcomes. Results: Relative to average-duration sleepers, a smaller percentage of short-duration sleepers mentioned breakfast, lunch (women only), and dinner in the recall (P ≤ 0.04). They also reported a lower mean percentage of energy from main meals but higher energy from all snacks (P ≤ 0.0004) and after 2000 h (P = 0.03). Short-duration sleepers reported the earliest eating time of the first episode and the latest time of the last eating episode. Absolute amounts of sugar and caffeine and percentage of energy from beverages (women only) were higher in short-duration sleepers. However, the total number of eating episodes and energy intake were not related with sleep duration. Conclusions: Short-duration sleepers began eating earlier and ended their eating later in the day, but despite the longer eating period, they did not report more eating events. Profiles of the relative contribution of main meals and snacks, at or after 2000 h eating, and beverages in short-duration sleepers were suggestive of eating behaviors that may increase energy intake, but 24-h energy intake did not differ among categories of sleep duration. PMID:25057157

  5. QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL Population

    PubMed Central

    Hu, Shuaidong; Lübberstedt, Thomas; Zhao, Guangwu; Lee, Michael

    2016-01-01

    Low temperature is the primary factor to affect maize sowing in early spring. It is, therefore, vital for maize breeding programs to improve tolerance to low temperatures at seed germination stage. However, little is known about maize QTL involved in low-temperature germination ability. 243 lines of the intermated B73×Mo17 (IBM) Syn4 recombinant inbred line (RIL) population was used for QTL analysis of low-temperature germination ability. There were significant differences in germination-related traits under both conditions of low temperature (12°C/16h, 18°C/8h) and optimum temperature (28°C/24h) between the parental lines. Only three QTL were identified for controlling optimum-temperature germination rate. Six QTL controlling low-temperature germination rate were detected on chromosome 4, 5, 6, 7 and 9, and contribution rate of single QTL explained between 3.39%~11.29%. In addition, six QTL controlling low-temperature primary root length were detected in chromosome 4, 5, 6, and 9, and the contribution rate of single QTL explained between 3.96%~8.41%. Four pairs of QTL were located at the same chromosome position and together controlled germination rate and primary root length under low temperature condition. The nearest markers apart from the corresponding QTL (only 0.01 cM) were umc1303 (265.1 cM) on chromosome 4, umc1 (246.4 cM) on chromosome 5, umc62 (459.1 cM) on chromosome 6, bnl14.28a (477.4 cM) on chromosome 9, respectively. A total of 3155 candidate genes were extracted from nine separate intervals based on the Maize Genetics and Genomics Database (http://www.maizegdb.org). Five candidate genes were selected for analysis as candidates putatively affecting seed germination and seedling growth at low temperature. The results provided a basis for further fine mapping, molecular marker assisted breeding and functional study of cold-tolerance at the stage of seed germination in maize. PMID:27031623

  6. Different proteins and biopeptides differently affect satiety and anorexigenic/orexigenic hormones in healthy humans.

    PubMed

    Diepvens, K; Häberer, D; Westerterp-Plantenga, M

    2008-03-01

    We investigated the effects of whey protein (WP), pea protein hydrolysate (PPH), a combination of WP+PPH and control (milk protein (MP) which consists of 80% casein and 20% WP) on appetite ratings, postprandial changes in hunger/satiety hormones and energy intake (EI). A randomized, crossover design which consisted of 2 parts (experiment 1 and 2). The peptides to be tested were provided as part of a shake (1024 kJ; en% P/F/C: 25/33/42) which contained either 15 g WP, 15 g PPH, a combination of 7.5 g WP and 7.5 g PPH (WP+PPH) or 15 g MP. 39 subjects (BMI: 27.6+/-1.7 kg m(-2); age: 42.3+/-13.8 years). In experiment 1 (duration 4 h), appetite profile was measured and blood samples were taken for analysis of hunger/satiety hormones and glucose. In experiment 2 (duration 7 h), appetite profile and EI (180 min after consumption of the shake) were measured. Some indications of lower hunger (experiment 1), desire to eat (experiment 2) and thirst (experiment 1 and 2) were shown after consumption of PPH compared to MP or WP+PPH (P<0.05). A longer intermeal interval and a higher satiety index were suggested after consumption of PPH. Both PPH and WP lead to greater satiety (experiment 2) and fullness (experiment 2) compared to MP and WP+PPH (P<0.05). For WP, a positive correlation between insulin and both cholecystokinine (CCK) and glucagon like peptide-1 (GLP-1) was observed (P<0.05). However, both CCK and GLP-1 were increased by MP (P<0.05), peptide YY (PYY) was stimulated by WP+PPH, while the decline in ghrelin was larger (P<0.05). No effect on EI was seen. There was modest evidence with respect to satiety by PPH consumption. Different exogenous biopeptides produced differences in release of endogenous peptides that had inconsistent relationships with satiety. Therefore, evidence derived from a supposed biomarker for satiety does not guarantee the highest satiety.

  7. Structure cristalline du composé intermétallique Ni18Ge12

    PubMed Central

    Kars, Mohammed; Herrero, Adrian Gómez; Roisnel, Thierry; Rebbah, Allaoua; Otero-Diáz, L. Carlos

    2015-01-01

    Single crystals of octa­deca­nickel dodeca­germanide were grown by chemical transport reaction. The inter­metallic compound crystallizes in a superstructure of the hexa­gonal NiAs type (B8 type). All atoms in the asymmetric unit lie on special positions except one Ni atom (two Ni atoms have site symmetry -6.. and another one has site symmetry .2. while the Ge atoms have site symmetries 32., m.. and 3..). In the structure, the Ni atoms are arranged in 11- or 13-vertex polyhedra (CN = 11–13). The coordination polyhedra of the Ge atoms are bicapped square anti­prisms (CN = 10) or 11-vertex polyhedra (CN = 11). The structure exhibits strong Ge⋯Ni inter­actions, but no close Ge⋯Ge contacts are observed. The Ni atoms with CN = 13 form infinite chains along [001] with an Ni—Ni distance of 2.491 (2) Å. PMID:25844198

  8. Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors Showing Partial Cross-Resistance with Quinolones.

    PubMed

    Jeannot, Frédéric; Taillier, Thomas; Despeyroux, Pierre; Renard, Stéphane; Rey, Astrid; Mourez, Michaël; Poeverlein, Christoph; Khichane, Imène; Perrin, Marc-Antoine; Versluys, Stéphanie; Stavenger, Robert A; Huang, Jianzhong; Germe, Thomas; Maxwell, Anthony; Cao, Sha; Huseby, Douglas L; Hughes, Diarmaid; Bacqué, Eric

    2018-04-26

    In our quest for new antibiotics able to address the growing threat of multidrug resistant infections caused by Gram-negative bacteria, we have investigated an unprecedented series of non-quinolone bacterial topoisomerase inhibitors from the Sanofi patrimony, named IPYs for imidazopyrazinones, as part of the Innovative Medicines Initiative (IMI) European Gram Negative Antibacterial Engine (ENABLE) organization. Hybridization of these historical compounds with the quinazolinediones, a known series of topoisomerase inhibitors, led us to a novel series of tricyclic IPYs that demonstrated potential for broad spectrum activity, in vivo efficacy, and a good developability profile, although later profiling revealed a genotoxicity risk. Resistance studies revealed partial cross-resistance with fluoroquinolones (FQs) suggesting that IPYs bind to the same region of bacterial topoisomerases as FQs and interact with at least some of the keys residues involved in FQ binding.

  9. Ada Compiler Validation Summary Report: Certificate Number: 890409W1. 10063, TeleSoft, TeleGen2 Ada Development System for VAX to E68K, Version 3.23, VAXserver 3602 Host and Motorola MVME117 (MC68010) Target

    DTIC Science & Technology

    1989-04-09

    01hc ’i.’ f’Pf a- ebc 2i1o.-fer-er~hfom Repo.) tUEFCTE $UP1 * ta ~ (Con’rj 01’?Cre V Pot s’o fneccksa’) ortoiorM’f, by blDc n fumYber) Ada Prcr-7n...CLA53SIF1CA1,O0s or IMIS PA ,j (AhnDetsinfree1 AVF Control Number: AVF-VSP-267.0539 69-01-25-TEL Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number...pragma images controls the creation and allocation of the image table for a specified enumeration type. The default is Deferred, which saves space in the

  10. Quantitative weight of evidence assessment of risk to honeybee colonies from use of imidacloprid, clothianidin, and thiamethoxam as seed treatments: a postscript.

    PubMed

    Solomon, Keith R; Stephenson, Gladys L

    2017-01-01

    This paper is a postscript to the four companion papers in this issue of the Journal (Solomon and Stephenson 2017a , 2017b ; Stephenson and Solomon 2017a , 2017b ). The first paper in the series described the conceptual model and the methods of the QWoE process. The other three papers described the application of the QWoE process to studies on imidacloprid (IMI), clothianidin (CTD), and thiamethoxam (TMX). This postscript was written to summarize the utility of the methods used in the quantitative weight of evidence (QWoE), the overall relevance of the results, and the environmental implications of the findings. Hopefully, this will be helpful to others who wish to conduct QWoEs and use these methods in assessment of risks.

  11. Antimicrobial susceptibilities and random amplified polymorphic DNA-PCR fingerprint characterization of Lactococcus lactis ssp. lactis and Lactococcus garvieae isolated from bovine intramammary infections.

    PubMed

    Plumed-Ferrer, C; Barberio, A; Franklin-Guild, R; Werner, B; McDonough, P; Bennett, J; Gioia, G; Rota, N; Welcome, F; Nydam, D V; Moroni, P

    2015-09-01

    In total, 181 streptococci-like bacteria isolated from intramammary infections (IMI) were submitted by a veterinary clinic to Quality Milk Production Services (QMPS, Cornell University, Ithaca, NY). The isolates were characterized by sequence analysis, and 46 Lactococcus lactis ssp. lactis and 47 Lactococcus garvieae were tested for susceptibility to 17 antibiotics. No resistant strains were found for β-lactam antibiotics widely used in clinical practice (penicillin, ampicillin, and amoxicillin), and all minimum inhibitory concentrations (MIC) were far from the resistance breakpoints. Eight strains had MIC intermediate to cefazolin. The random amplification of polymorphic DNA (RAPD)-PCR fingerprint patterns showed a slightly higher heterogeneity for Lc. lactis ssp. lactis isolates than for Lc. garvieae isolates. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. The Joint European Compound Library: boosting precompetitive research.

    PubMed

    Besnard, Jérémy; Jones, Philip S; Hopkins, Andrew L; Pannifer, Andrew D

    2015-02-01

    The Joint European Compound Library (JECL) is a new high-throughput screening collection aimed at driving precompetitive drug discovery and target validation. The JECL has been established with a core of over 321,000 compounds from the proprietary collections of seven pharmaceutical companies and will expand to around 500,000 compounds. Here, we analyse the physicochemical profile and chemical diversity of the core collection, showing that the collection is diverse and has a broad spectrum of predicted biological activity. We also describe a model for sharing compound information from multiple proprietary collections, enabling diversity and quality analysis without disclosing structures. The JECL is available for screening at no cost to European academic laboratories and SMEs through the IMI European Lead Factory (http://www.europeanleadfactory.eu/). Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Meteor Observation in a Group

    NASA Astrophysics Data System (ADS)

    Zimnikoval, Peter

    2010-08-01

    Observation in former Czechoslovakia has more than 100 years tradition. These activities started in Czech part of the republic, mostly. More serious and systematic observations began in second half of the 20-th century. Important role played the International Geophysical Year 1957/58. Part of this event was International Meteor Year. Czechoslovakian astronomers were accredited as main organisers of the IMY. It was improved observe methods for this reason. High role in meteor observations has establishment of public observatories in Slovakia in 70-ties, too. Beside of popularization of astronomy one of main task was to organise amateur observations. Important role had collaboration of Copernicus Observatory and planetarium Brno (now Czech republic) and observatory Banská Bystrica from 1972. Main purpose of the collaboration was organising of so-called National Meteor Expeditions. These expeditions runs till 1988. Tradition of expeditions continues in Slovakia until today.

  14. Television Viewing Does Not Have to Be Sedentary: Motivation to Participate in a TV Exercise Program

    PubMed Central

    Meis, Jessie J. M.; Kremers, Stef P. J.; Bouman, Martine P. A.

    2012-01-01

    The present study explored which underlying motivations induced people to participate in a television exercise program called “The Netherlands on the Move!-television” (NOM-tv). A cross-sectional study was carried out among 1,349 viewers of NOM-tv. The respondents completed the intrinsic motivation inventory (IMI), assessing their levels of intrinsic motivation towards participating in the NOM-tv exercises. The results showed that higher levels of intrinsic motivation (i.e. enjoying the NOM-tv exercises, feeling competent to perform this activity, and willingness to put effort into the exercises) were the most important predictive factors of more frequent participation in the NOM-tv exercises. Future screen-based interventions to reduce sedentary behavior should aim especially at encouraging people's intrinsic orientations towards physical activity in an autonomy-supportive way. PMID:22187637

  15. Chemical Stability of Telavancin in Elastomeric Pumps.

    PubMed

    Sand, Patrick; Aladeen, Traci; Kirkegaard, Paul; LaChance, Dennis; Slover, Christine

    2015-12-01

    VIBATIV is a once-daily, injectable lipoglycopeptide antibiotic approved in the U.S. for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. In addition, VIBATIV is approved in the U.S. for the treatment of adult patients with complicated skin & skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains. To evaluate the chemical stability of telavancin (Vibativ; Theravance Biopharma US, Inc, Northbrook, Illinois), a lipoglycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus, in 2 types of elastomeric pumps, the Intermate Infusion System (Baxter International Inc) and the Homepump Eclipse (I-Flow Corporation). Different sizes of the Baxter (Ontario, Canada) (105 mL and 275 mL) and I-Flow (Stoughton, Massachusetts) (100 mL and 250 mL) pumps were compared with glass controls. The telavancin drug product was reconstituted and diluted to concentrations of 0.6 mg/mL and 8.0 mg/mL using either 0.9% saline, 5% dextrose in water, or sterilized water for injection (0.6 mg/mL telavancin) or saline (8.0 mg/mL telavancin) followed by Ringer's Lactate solution. Pumps were filled and stored at 2°C to 8°C, protected from light. Aliquots from both pump types and for all telavancin reconstitution/dilution schemes and concentrations were taken over a period of 8 days and analyzed for appearance, pH, telavancin concentration and purity, and degradation products. The pH of all pump solutions remained consistent throughout the 8-day analysis period, within a range of 4.6 to 5.7 for the 0.6 mg/mL and 4.4 to 4.9 for the 8.0 mg/mL telavancin solutions. There was no significant change in the chromatographic purity for any of the pump solutions examined. All decreases in telavancin concentration were ≤2.7%. Comparison of each test sample solution to the corresponding glass control indicated no loss of active drug due to absorption by the elastomeric material of the pumps. The greatest increase in the amount of total degradants observed over the 8-day period was ~0.7 w/w%. The results of this study indicate that telavancin remains chemically stable when diluted in the Intermate Infusion System and the Homepump Eclipse elastomeric pumps and stored at 2°C to 8°C for up to 8 days protected from light at the concentration range and dilution schemes evaluated.

  16. Vulvovaginite : Dépistage et prise en charge de la trichomonase, de la candidose vulvovaginale et de la vaginose bactérienne.

    PubMed

    van Schalkwyk, Julie; Yudin, Mark H

    2016-12-01

    Analyser les données probantes et formuler des recommandations quant au dépistage et à la prise en charge de la candidose vulvovaginale, de la trichomonase et de la vaginose bactérienne. Parmi les issues évaluées, on trouve l'efficacité de l'antibiothérapie, les taux de guérison en ce qui concerne les infections simples et compliquées, et les implications de ces pathologies pendant la grossesse. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE, EMBASE, CINAHL et The Cochrane Library en juin 2013 au moyen d'un vocabulaire contrôlé (p. ex. « vaginitis », « trichomoniasis », « vaginal candidiasis ») et de mots clés (p. ex. « bacterial vaginosis », « yeast », « candidiasis », « trichomonas vaginalis », « trichomoniasis », « vaginitis », « treatment ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Aucune restriction n'a été appliquée en matière de date, mais les résultats ont été limités aux documents rédigés en anglais ou en français. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en mai 2014. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques et auprès de sociétés de spécialité médicale nationales et internationales. La qualité des résultats est évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). DéCLARATIONS SOMMAIRES: RECOMMANDATIONS. Copyright © 2016. Published by Elsevier Inc.

  17. Isocyanates and work-related asthma: Findings from California, Massachusetts, Michigan, and New Jersey, 1993-2008.

    PubMed

    Lefkowitz, Daniel; Pechter, Elise; Fitzsimmons, Kathleen; Lumia, Margaret; Stephens, Alicia C; Davis, Letitia; Flattery, Jennifer; Weinberg, Justine; Harrison, Robert J; Reilly, Mary Jo; Filios, Margaret S; White, Gretchen E; Rosenman, Kenneth D

    2015-11-01

    Isocyanates remain a leading cause of work-related asthma (WRA). Two independent data systems were analyzed for the period 1993-2008: (1) State-based WRA case surveillance data on persons with isocyanate-induced WRA from four states, and (2) Occupational Safety and Health Administration (OSHA) Integrated Management Information System (IMIS) isocyanate air sampling results. We identified 368 cases of isocyanate-induced WRA from 32 industries and 678 OSHA isocyanate air samples with detectable levels from 31 industries. Seventeen industries were unique to one or the other dataset. Isocyanate-induced WRA continues to occur in a wide variety of industries. Two data systems uncovered industries with isocyanate exposures and/or illness. Improved control measures and standards, including medical surveillance, are needed. More emphasis is needed on task-specific guidance, spill clean-up procedures, skin and respiratory protection, and targeted medical monitoring to mitigate the hazards of isocyanate use. © 2015 Wiley Periodicals, Inc.

  18. Talaromyces emersonii thermostable enzyme systems and their applications in wheat baking systems.

    PubMed

    Waters, Deborah M; Murray, Patrick G; Ryan, Liam A; Arendt, Elke K; Tuohy, Maria G

    2010-06-23

    In this study, novel extracellular thermozymes were produced by the thermophilic fungus Talaromyces emersonii (IMI 392299) on low-cost carbon inducers. This paper reports the cocktail characterization, substrate hydrolysis studies, and their application in baking. Relevant enzymes were optimally active at pH 4.5-5.0 and 70 degrees C. Model studies confirmed production of significant levels of yeast monosaccharide sugars during cereal flour hydrolysis. The "thermozyme cocktails" are thermostable secreted T. emersonii enzyme blends. In baking trials, these thermozyme cocktails showed significant improvements in bread quality with respect to hardness, staling, and loaf volume (p < 0.5). Thermozyme cocktail B- treated loaf volume was 23.2% greater than the control and 49.5% softer. Staling analysis showed that bread treated with cocktail B was 41.7% softer than the control. This is the first report of T. emersonii thermozymes positively influencing bread quality.

  19. Costs of using motivational interviewing for problem drinking in the U.S. Air Force.

    PubMed

    Cowell, Alexander J; Brown, Janice M; Wedehase, Brendan J; Masuda, Yuta J

    2010-12-01

    Despite the popularity of motivational interviewing (MI) to address heavy drinking, limited evidence exists on the costs of using MI to address heavy drinking. This study examines the costs of using MI to address heavy drinking at four U.S. Air Force (USAF) bases. Clients were referred to and assessed at a base program to address their drinking as a result of an incident; those who were not alcohol dependent were invited to participate in the study. Participants consented and were randomly assigned to one of three intervention arms: individual MI (IMI), group MI (GMI), and Substance Abuse Awareness Seminar (SAAS). Three cost perspectives were taken: USAF, client, and the two combined. Data were collected from bases and public sources. The start-up cost per base ranged from $1340 to $2400 per provider staff member. Average implementation costs across bases were highest for the SAAS intervention ($148 per client).

  20. Thermal Testing and Analysis of an Efficient High-Temperature Multi-Screen Internal Insulation

    NASA Technical Reports Server (NTRS)

    Weiland, Stefan; Handrick, Karin; Daryabeigi, Kamran

    2007-01-01

    Conventional multi-layer insulations exhibit excellent insulation performance but they are limited to the temperature range to which their components reflective foils and spacer materials are compatible. For high temperature applications, the internal multi-screen insulation IMI has been developed that utilizes unique ceramic material technology to produce reflective screens with high temperature stability. For analytical insulation sizing a parametric material model is developed that includes the main contributors for heat flow which are radiation and conduction. The adaptation of model-parameters based on effective steady-state thermal conductivity measurements performed at NASA Langley Research Center (LaRC) allows for extrapolation to arbitrary stack configurations and temperature ranges beyond the ones that were covered in the conductivity measurements. Experimental validation of the parametric material model was performed during the thermal qualification test of the X-38 Chin-panel, where test results and predictions showed a good agreement.

  1. Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells.

    PubMed

    Park, Eunkyue; Levis, William R; Greig, Nigel; Jung, Euisun; Schuller-Levis, Georgia

    2010-04-01

    Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).

  2. Reports of the U.S. - U.S.S.R. Weddell Polynya Expedition, October-November 1981. Volume 6. Upper-Air Data.

    DTIC Science & Technology

    1983-05-01

    65 0 7 *.’• 7P 72 66 i-3 r.f 5? 50 «» 36 25 E IMi 1 IE*: Hr-.n (KG/«•»3 > i|6 iEC -J sprt r (8/° ) O.7708 0.6677 0.751" 0•652 2...16974. 73.5 17025 . 72.9 17077. 72.3 1712t?. 71.7 1718ü. 71.1 17233. 70.5 17277. 73.0 17331. o9.4 I <c > —1 1 • ’- -el.f -fei. I -11.1...10.3 99.9 100. 0.1903 0.1743 0.7829 4416. 527.9 -35.5 12.1 12.1 -35.5 KC. 0.2123 0.1936 0.7740 4464. 524.3 -3 5.6 12.5 12.6 99.9 ISO . 0.2093 0.191C

  3. Perceptions of motivational climate and teachers' strategies to sustain discipline as predictors of intrinsic motivation in physical education.

    PubMed

    Gutiérrez, Melchor; Ruiz, Luis-Miguel; López, Esther

    2010-11-01

    This study examined the relationship among pupils' perceptions of the motivational climate, pupils' perceptions of teachers' strategies to maintain discipline and pupils' intrinsic motivation in physical education. A sample of 2189 Spanish adolescents, ages 13 to 17 years, completed Spanish versions of the EPCM, SSDS, and IMI. Confirmatory factor analyses were carried out to confirm the factorial validity of the scales. Then, the relationship among the variables was explored through Structural Equation Modelling. The most important predictors of pupils' intrinsic motivation were the perceived mastery climate, and perceived teachers' emphasis on intrinsic reasons to maintain discipline. Perceived performance climate and perceived teachers' strategies to maintain discipline based on introjected reasons and indifference, predicted pupils' tension-pressure. Results are discussed in the context of theoretical propositions of self-determination theory and practical issues of enhancing adolescents' motivation in physical education.

  4. Multiplex PCR for Rapid Detection of Genes Encoding Class A Carbapenemases

    PubMed Central

    Hong, Sang Sook; Kim, Kyeongmi; Huh, Ji Young; Jung, Bochan; Kang, Myung Seo

    2012-01-01

    In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-β-lactamase nonproducers. PMID:22950072

  5. Multiplex PCR for rapid detection of genes encoding class A carbapenemases.

    PubMed

    Hong, Sang Sook; Kim, Kyeongmi; Huh, Ji Young; Jung, Bochan; Kang, Myung Seo; Hong, Seong Geun

    2012-09-01

    In recent years, there have been increasing reports of KPC-producing Klebsiella pneumoniae in Korea. The modified Hodge test can be used as a phenotypic screening test for class A carbapenamase (CAC)-producing clinical isolates; however, it does not distinguish between carbapenemase types. The confirmation of type of CAC is important to ensure optimal therapy and to prevent transmission. This study applied a novel multiplex PCR assay to detect and differentiate CAC genes in a single reaction. Four primer pairs were designed to amplify fragments encoding 4 CAC families (SME, IMI/NMC-A, KPC, and GES). The multiplex PCR detected all genes tested for 4 CAC families that could be differentiated by fragment size according to gene type. This multiplex PCR offers a simple and useful approach for detecting and distinguishing CAC genes in carbapenem-resistant strains that are metallo-β-lactamase nonproducers.

  6. Virtual reality to augment robot-assisted gait training in non-ambulatory patients with a subacute stroke: a pilot randomized controlled trial.

    PubMed

    Bergmann, Jeannine; Krewer, Carmen; Bauer, Petra; Koenig, Alexander; Riener, Robert; Müller, Friedemann

    2018-06-01

    Active performance is crucial for motor learning, and, together with motivation, is believed to be associated with a better rehabilitation outcome. Virtual reality (VR) is an innovative approach to engage and motivate patients during training. There is promising evidence for its efficiency in retraining upper limb function. However, there is insufficient proof for its effectiveness in gait training. To evaluate the acceptability of robot-assisted gait training (RAGT) with and without VR and the feasibility of potential outcome measures to guide the planning of a larger randomized controlled trial (RCT). Single-blind randomized controlled pilot trial with two parallel arms. Rehabilitation hospital. Twenty subacute stroke patients (64±9 years) with a Functional Ambulation Classification (FAC) ≤2. Twelve sessions (over 4 weeks) of either VR-augmented RAGT (intervention group) or standard RAGT (control group). Acceptability of the interventions (drop-out rate, questionnaire), patients' motivation (Intrinsic Motivation Inventory [IMI], individual mean walking time), and feasibility of potential outcome measures (completion rate and response to interventions) were determined. We found high acceptability of repetitive VR-augmented RAGT. The drop-out rate was 1/11 in the intervention and 4/14 in the control group. Patients of the intervention group spent significantly more time walking in the robot than the control group (per session and total walking time; P<0.03). In both groups, motivation measured with the IMI was high over the entire intervention period. The felt pressure and tension significantly decreased in the intervention group (P<0.01) and was significantly lower than in the control group at the last therapy session (r=-0.66, P=0.005). The FAC is suggested as a potential primary outcome measure for a definitive RCT, as it could be assessed in all patients and showed significant response to interventions (P<0.01). We estimated a sample size of 44 for a future RCT. VR-augmented RAGT resulted in high acceptability and motivation, and in a reduced drop-out rate and an extended training time compared to standard RAGT. This pilot trial provides guidance for a prospective RCT on the effectiveness of VR-augmented RAGT. VR might be a promising approach to enrich and improve gait rehabilitation after stroke.

  7. Methicillin-resistant Staphylococcus aureus (MRSA) is associated with low within-herd prevalence of intra-mammary infections in dairy cows: Genotyping of isolates.

    PubMed

    Luini, M; Cremonesi, P; Magro, G; Bianchini, V; Minozzi, G; Castiglioni, B; Piccinini, R

    2015-08-05

    Staphylococcus aureus is one of the most common mastitis-causing pathogens worldwide. In the last decade, livestock-associated methicillin-resistant S. aureus (LA-MRSA) infections have been described in several species, included the bovines. Hence, this paper investigates the diffusion of MRSA within Italian dairy herds; the strains were further characterized using a DNA microarray, which detects 330 different sequences, including the methicillin-resistance genes mecA and mecC and SCCmec typing. The analysis of overall patterns allows the assignment to Clonal Complexes (CC). Overall 163 S. aureus isolates, collected from quarter milk samples in 61 herds, were tested. MRSA strains were further processed using spa typing. Fifteen strains (9.2%), isolated in 9 herds (14.75%), carried mecA, but none harboured mecC. MRSA detection was significantly associated (P<0.011) with a within-herd prevalence of S. aureus intra-mammary infections (IMI) ≤5%. Ten MRSA strains were assigned to CC398, the remaining ones to CC97 (n=2), CC1 (n=2) or CC8 (n=1). In 3 herds, MRSA and MSSA co-existed: CC97-MRSA with CC398-MSSA, CC1-MRSA with CC8-MSSA and CC398-MRSA with CC126-MSSA. The results of spa typing showed an overall similar profile of the strains belonging to the same CC: t127-CC1, t1730-CC97, t899 in 8 out of 10 CC398. In the remaining 2 isolates a new spa type, t14644, was identified. The single CC8 was a t3092. The SCCmec cassettes were classified as type IV, type V or type IV/V composite. All or most strains harboured the genes encoding the β-lactamase operon and the tetracycline resistance. Streptogramin resistance gene was related to CC398. Enterotoxin and leukocidin genes were carried only by CC1, CC8 and CC97-MRSA. The persistence of MRSA clones characterized by broader host range, in epidemiologically unrelated areas and in dairy herds with low prevalence of S. aureus IMI, might enhance the risk for adaptation to human species. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Exploring the genetic architecture and improving genomic prediction accuracy for mastitis and milk production traits in dairy cattle by mapping variants to hepatic transcriptomic regions responsive to intra-mammary infection.

    PubMed

    Fang, Lingzhao; Sahana, Goutam; Ma, Peipei; Su, Guosheng; Yu, Ying; Zhang, Shengli; Lund, Mogens Sandø; Sørensen, Peter

    2017-05-12

    A better understanding of the genetic architecture of complex traits can contribute to improve genomic prediction. We hypothesized that genomic variants associated with mastitis and milk production traits in dairy cattle are enriched in hepatic transcriptomic regions that are responsive to intra-mammary infection (IMI). Genomic markers [e.g. single nucleotide polymorphisms (SNPs)] from those regions, if included, may improve the predictive ability of a genomic model. We applied a genomic feature best linear unbiased prediction model (GFBLUP) to implement the above strategy by considering the hepatic transcriptomic regions responsive to IMI as genomic features. GFBLUP, an extension of GBLUP, includes a separate genomic effect of SNPs within a genomic feature, and allows differential weighting of the individual marker relationships in the prediction equation. Since GFBLUP is computationally intensive, we investigated whether a SNP set test could be a computationally fast way to preselect predictive genomic features. The SNP set test assesses the association between a genomic feature and a trait based on single-SNP genome-wide association studies. We applied these two approaches to mastitis and milk production traits (milk, fat and protein yield) in Holstein (HOL, n = 5056) and Jersey (JER, n = 1231) cattle. We observed that a majority of genomic features were enriched in genomic variants that were associated with mastitis and milk production traits. Compared to GBLUP, the accuracy of genomic prediction with GFBLUP was marginally improved (3.2 to 3.9%) in within-breed prediction. The highest increase (164.4%) in prediction accuracy was observed in across-breed prediction. The significance of genomic features based on the SNP set test were correlated with changes in prediction accuracy of GFBLUP (P < 0.05). GFBLUP provides a framework for integrating multiple layers of biological knowledge to provide novel insights into the biological basis of complex traits, and to improve the accuracy of genomic prediction. The SNP set test might be used as a first-step to improve GFBLUP models. Approaches like GFBLUP and SNP set test will become increasingly useful, as the functional annotations of genomes keep accumulating for a range of species and traits.

  9. Scalable and expressive medical terminologies.

    PubMed

    Mays, E; Weida, R; Dionne, R; Laker, M; White, B; Liang, C; Oles, F J

    1996-01-01

    The K-Rep system, based on description logic, is used to represent and reason with large and expressive controlled medical terminologies. Expressive concept descriptions incorporate semantically precise definitions composed using logical operators, together with important non-semantic information such as synonyms and codes. Examples are drawn from our experience with K-Rep in modeling the InterMed laboratory terminology and also developing a large clinical terminology now in production use at Kaiser-Permanente. System-level scalability of performance is achieved through an object-oriented database system which efficiently maps persistent memory to virtual memory. Equally important is conceptual scalability-the ability to support collaborative development, organization, and visualization of a substantial terminology as it evolves over time. K-Rep addresses this need by logically completing concept definitions and automatically classifying concepts in a taxonomy via subsumption inferences. The K-Rep system includes a general-purpose GUI environment for terminology development and browsing, a custom interface for formulary term maintenance, a C+2 application program interface, and a distributed client-server mode which provides lightweight clients with efficient run-time access to K-Rep by means of a scripting language.

  10. Water Storage Changes over the Tibetan Plateau Revealed by GRACE Mission

    NASA Astrophysics Data System (ADS)

    Guo, Jinyun; Mu, Dapeng; Liu, Xin; Yan, Haoming; Sun, Zhongchang; Guo, Bin

    2016-04-01

    We use GRACE gravity data released by the Center for Space Research (CSR) and the Groupe de Recherches en Geodesie Spatiale (GRGS) to detect the water storage changes over the Tibetan Plateau (TP). A combined filter strategy is put forward to process CSR RL05 data to remove the effect of striping errors. After the correction for GRACE by GLDAS and ICE-5G, we find that TP has been overall experiencing the water storage increase during 2003-2012. During the same time, the glacier over the Himalayas was sharply retreating. Interms of linear trends, CSR's results derived by the combined filter are close to GRGS RL03 with the Gaussian filter of 300-km window. The water storage increasing rates determined from CSR's RL05 products in the interior TP, Karakoram Mountain, Qaidam Basin, Hengduan Mountain, and middle Himalayas are 9.7, 6.2, 9.1,-18.6, and-20.2 mm/yr, respectively. These rates from GRGS's RL03 products are 8.6, 5.8, 10.5,-19.3 and-21.4 mm/yr, respectively.

  11. Chemical Stability of Telavancin in Elastomeric Pumps☆

    PubMed Central

    Sand, Patrick; Aladeen, Traci; Kirkegaard, Paul; LaChance, Dennis; Slover, Christine

    2015-01-01

    Background VIBATIV is a once-daily, injectable lipoglycopeptide antibiotic approved in the U.S. for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. In addition, VIBATIV is approved in the U.S. for the treatment of adult patients with complicated skin & skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains. Objective To evaluate the chemical stability of telavancin (Vibativ; Theravance Biopharma US, Inc, Northbrook, Illinois), a lipoglycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus, in 2 types of elastomeric pumps, the Intermate Infusion System (Baxter International Inc) and the Homepump Eclipse (I-Flow Corporation). Methods Different sizes of the Baxter (Ontario, Canada) (105 mL and 275 mL) and I-Flow (Stoughton, Massachusetts) (100 mL and 250 mL) pumps were compared with glass controls. The telavancin drug product was reconstituted and diluted to concentrations of 0.6 mg/mL and 8.0 mg/mL using either 0.9% saline, 5% dextrose in water, or sterilized water for injection (0.6 mg/mL telavancin) or saline (8.0 mg/mL telavancin) followed by Ringer’s Lactate solution. Pumps were filled and stored at 2°C to 8°C, protected from light. Aliquots from both pump types and for all telavancin reconstitution/dilution schemes and concentrations were taken over a period of 8 days and analyzed for appearance, pH, telavancin concentration and purity, and degradation products. Results The pH of all pump solutions remained consistent throughout the 8-day analysis period, within a range of 4.6 to 5.7 for the 0.6 mg/mL and 4.4 to 4.9 for the 8.0 mg/mL telavancin solutions. There was no significant change in the chromatographic purity for any of the pump solutions examined. All decreases in telavancin concentration were ≤2.7%. Comparison of each test sample solution to the corresponding glass control indicated no loss of active drug due to absorption by the elastomeric material of the pumps. The greatest increase in the amount of total degradants observed over the 8-day period was ~0.7 w/w%. Conclusions The results of this study indicate that telavancin remains chemically stable when diluted in the Intermate Infusion System and the Homepump Eclipse elastomeric pumps and stored at 2°C to 8°C for up to 8 days protected from light at the concentration range and dilution schemes evaluated. PMID:26649079

  12. Modification of the feeding behavior of dairy cows through live yeast supplementation.

    PubMed

    DeVries, T J; Chevaux, E

    2014-10-01

    The objective of this study was to determine if the feeding behavior of dairy cows is modified through live yeast supplementation. Twelve lactating Holstein dairy cows (2 primiparous and 10 multiparous) were individually exposed, in a replicated crossover design, to each of 2 treatment diets (over 35-d periods): (1) a control TMR and (2) a control TMR plus 1 × 10(10) cfu/head per day of live yeast (Saccharomyces cerevisiae CNCM I-1077; Levucell SC20; Lallemand Animal Nutrition, Montreal, QC, Canada). Milk production, feeding, and rumination behavior were electronically monitored for each animal for the last 7 d of each treatment period. Milk samples were collected for the last 6 d of each period for milk component analysis. Dry matter intake (28.3 kg/d), eating time (229.3 min/d), and rate (0.14 kg of dry matter/min) were similar between treatments. With yeast supplementation, meal criteria (minimum intermeal interval) were shorter (20.0 vs. 25.8 min), translating to cows tending to have more meals (9.0 vs. 7.8 meals/d), which tended to be smaller in size (3.4 vs. 3.8 kg/meal). Yeast-supplemented cows also tended to ruminate longer (570.3 vs. 544.9 min/d). Milk yield (45.8 kg/d) and efficiency of production (1.64 kg of milk/kg of dry matter intake) were similar between treatments. A tendency for higher milk fat percent (3.71 vs. 3.55%) and yield (1.70 vs. 1.63 kg/d) was observed when cows were supplemented with yeast. No differences in milk fatty acid composition were observed, with the exception of a tendency for a greater concentration of 18:2 cis-9,cis-12 fatty acid (2.71 vs. 2.48% of total fatty acids) with yeast supplementation. Yeast-supplemented cows had lower mean ruminal temperature (38.4 vs. 38.5 °C) and spent less time with rumen temperature above 39.0 °C (353.1 vs. 366.9 min/d), potentially indicating improved rumen pH conditions. Overall, the results show that live yeast supplementation tended to improve meal patterns and rumination, rumen temperature, and milk fat production. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Novel agents in CNS myeloma treatment.

    PubMed

    Gozzetti, Alessandro; Cerase, Alfonso

    2014-01-01

    Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

  14. Diplogelasinospora grovesii IMI 171018 immobilized in polyurethane foam. An efficient biocatalyst for stereoselective reduction of ketones.

    PubMed

    Quezada, M A; Carballeira, J D; Sinisterra, J V

    2012-05-01

    Diplogelasinospora grovesii has been reported as a very active biocatalyst in the reduction of ketones. Along the text, the properties of this filamentous fungus as an immobilized catalyst are described. For this purpose, several immobilization supports as agar and polyurethane foam were tested. Experimental assays were also performed to test different co-substrates for the regeneration of the required enzyme cofactor. The fungus immobilized in polyurethane foam lead to the most stable and active catalyst. This derivative, using i-PrOH as co-substrate, could be reused at least 18 times without appreciable activity loss (>90% activity remains). Kinetic runs experiments shown that the reduction of cyclohexanone, selected as model substrate, followed a pseudo-first kinetic order and that the rate controlling step was the mass transfer through the cell wall. The deactivation kinetic constants were also determined. The reduction of different chiral ketones showed that the ketone reductase activity followed the Prelog's rule. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Isocyanates and Work-Related Asthma: Findings From California, Massachusetts, Michigan, and New Jersey, 1993–2008

    PubMed Central

    Lefkowitz, Daniel; Pechter, Elise; Fitzsimmons, Kathleen; Lumia, Margaret; Stephens, Alicia C.; Davis, Letitia; Flattery, Jennifer; Weinberg, Justine; Harrison, Robert J.; Reilly, Mary Jo; Filios, Margaret S.; White, Gretchen E.; Rosenman, Kenneth D.

    2015-01-01

    Background Isocyanates remain a leading cause of work-related asthma (WRA). Methods Two independent data systems were analyzed for the period 1993–2008: (1) State-based WRA case surveillance data on persons with isocyanate-induced WRA from four states, and (2) Occupational Safety and Health Administration (OSHA) Integrated Management Information System (IMIS) isocyanate air sampling results. Results We identified 368 cases of isocyanate-induced WRA from 32 industries and 678 OSHA isocyanate air samples with detectable levels from 31 industries. Seventeen industries were unique to one or the other dataset. Conclusion Isocyanate-induced WRA continues to occur in a wide variety of industries. Two data systems uncovered industries with isocyanate exposures and/or illness. Improved control measures and standards, including medical surveillance, are needed. More emphasis is needed on task-specific guidance, spill clean-up procedures, skin and respiratory protection, and targeted medical monitoring to mitigate the hazards of isocyanate use. PMID:26351141

  16. Intrinsic motivation factors based on the self-determinant theory for regular breast cancer screening.

    PubMed

    Jung, Su Mi; Jo, Heui-Sug

    2014-01-01

    The purpose of this study was to identify factors of intrinsic motivation that affect regular breast cancer screening and contribute to development of a program for strategies to improve effective breast cancer screening. Subjects were residing in South Korea Gangwon-Province and were female over 40 and under 69 years of age. For the investigation, the Intrinsic Motivation Inventory (IMI) was modified to the situation of cancer screening and was used to survey 905 inhabitants. Multinominal logistic regression analyses were conducted for regular breast cancer screening (RS), one-time breast cancer screening (OS) and non-breast cancer screening (NS). For statistical analysis, IBM SPSS 20.0 was utilized. The determinant factors between RS and NS were "perceived effort and choice" and "stress and strain" - internal motivations related to regular breast cancer screening. Also, determinant factors between RS and OS are "age" and "perceived effort and choice" for internal motivation related to cancer screening. To increase regular screening, strategies that address individual perceived effort and choice are recommended.

  17. Cross border semantic interoperability for clinical research: the EHR4CR semantic resources and services

    PubMed Central

    Daniel, Christel; Ouagne, David; Sadou, Eric; Forsberg, Kerstin; Gilchrist, Mark Mc; Zapletal, Eric; Paris, Nicolas; Hussain, Sajjad; Jaulent, Marie-Christine; MD, Dipka Kalra

    2016-01-01

    With the development of platforms enabling the use of routinely collected clinical data in the context of international clinical research, scalable solutions for cross border semantic interoperability need to be developed. Within the context of the IMI EHR4CR project, we first defined the requirements and evaluation criteria of the EHR4CR semantic interoperability platform and then developed the semantic resources and supportive services and tooling to assist hospital sites in standardizing their data for allowing the execution of the project use cases. The experience gained from the evaluation of the EHR4CR platform accessing to semantically equivalent data elements across 11 European participating EHR systems from 5 countries demonstrated how far the mediation model and mapping efforts met the expected requirements of the project. Developers of semantic interoperability platforms are beginning to address a core set of requirements in order to reach the goal of developing cross border semantic integration of data. PMID:27570649

  18. Joint channel/frequency offset estimation and correction for coherent optical FBMC/OQAM system

    NASA Astrophysics Data System (ADS)

    Wang, Daobin; Yuan, Lihua; Lei, Jingli; wu, Gang; Li, Suoping; Ding, Runqi; Wang, Dongye

    2017-12-01

    In this paper, we focus on analysis of the preamble-based joint estimation for channel and laser-frequency offset (LFO) in coherent optical filter bank multicarrier systems with offset quadrature amplitude modulation (CO-FBMC/OQAM). In order to reduce the noise impact on the estimation accuracy, we proposed an estimation method based on inter-frame averaging. This method averages the cross-correlation function of real-valued pilots within multiple FBMC frames. The laser-frequency offset is estimated according to the phase of this average. After correcting LFO, the final channel response is also acquired by averaging channel estimation results within multiple frames. The principle of the proposed method is analyzed theoretically, and the preamble structure is thoroughly designed and optimized to suppress the impact of inherent imaginary interference (IMI). The effectiveness of our method is demonstrated numerically using different fiber and LFO values. The obtained results show that the proposed method can improve transmission performance significantly.

  19. Public-private partnership models in France and in Europe.

    PubMed

    Demotes-Mainard, Jacques; Canet, Emmanuel; Segard, Lionel

    2006-01-01

    The workshop entitled "Public-Private partnerships models in Europe-- comparison between France and European countries" brought together representatives of academia and industry, of national or European health research programs, of regional or national public-private partnership (PPP) initiatives, and of biotechnology with the following objectives: sharing a common vision on the needs, expectations and challenges of public-private partnership, based on the analysis of actual and original cases, and of new initiatives on public-private partnership, drawing conclusions and identifying key success factors, identifying trails for progress and drawing recommendations. The major event in this field is a European public-private partnership initiative between pharmaceutical industry (European Federation of Pharmaceultical Industry and Associations, EFPIA) and the European Commission (DG Research--health priority) resulting in the European Technology Platform project "Innovative Medicines Initiative" (IMI). Its architecture is based on the identification of the main bottlenecks to the development of innovative treatments (predictive pharmacology and toxicology, identification and validation of biomarkers, patients' recruitment, risk evaluation, and cooperation with the regulatory authorities). Simultaneously, initiatives both at the national and regional levels also foster PPP in the therapeutic field. Regional competitivity clusters acting in the biomedical sector, and national PPP calls such as the ANR (National Research Agency) RIB (Research and Innovation in Biotechnology) call are incentives for PPP projects. These regional and national PPP levels help public and private partners to further build consortia able to compete for EU-level calls, thus acting as incubators for EU PPP projects. In spite of incentives and of the regional and national structuring of PPP, weaknesses in the French system are linked to its fragmentation--multiple transfer agencies, multiple research organisations (operator or funding agency)--making contracts more difficult. This requires a simplified organisation, with a single referent per area (health, technology...). Improvement may also result from adaptation in the carreer, recruitment and mobility, from support to scientists in the management of projects, and from consistent support (without maintaining them artificially alive) to emerging companies from concept through clinical development. Pathways have been proposed to improve the efficiency of clinical research in France and Europe, involving the public hospital sector, and this requires the connection of disease-oriented networks and integrated infrastructures in Europe. As stated in the IMI strategic research agenda on efficacy, the quality of public infrastructures in Europe will be a key factor for its competitiveness and attractiveness for both academic and industry projects.

  20. Retraining and assessing hand movement after stroke using the MusicGlove: comparison with conventional hand therapy and isometric grip training

    PubMed Central

    2014-01-01

    Background It is thought that therapy should be functional, be highly repetitive, and promote afferent input to best stimulate hand motor recovery after stroke, yet patients struggle to access such therapy. We developed the MusicGlove, an instrumented glove that requires the user to practice gripping-like movements and thumb-finger opposition to play a highly engaging, music-based, video game. The purpose of this study was to 1) compare the effect of training with MusicGlove to conventional hand therapy 2) determine if MusicGlove training was more effective than a matched form of isometric hand movement training; and 3) determine if MusicGlove game scores predict clinical outcomes. Methods 12 chronic stroke survivors with moderate hemiparesis were randomly assigned to receive MusicGlove, isometric, and conventional hand therapy in a within-subjects design. Each subject participated in six one-hour treatment sessions three times per week for two weeks, for each training type, for a total of 18 treatment sessions. A blinded rater assessed hand impairment before and after each training type and at one-month follow-up including the Box and Blocks (B & B) test as the primary outcome measure. Subjects also completed the Intrinsic Motivation Inventory (IMI). Results Subjects improved hand function related to grasping small objects more after MusicGlove compared to conventional training, as measured by the B & B score (improvement of 3.21±3.82 vs. -0.29±2.27 blocks; P=0.010) and the 9 Hole Peg test (improvement of 2.14±2.98 vs. -0.85±1.29 pegs/minute; P=0.005). There was no significant difference between training types in the broader assessment batteries of hand function. Subjects benefited less from isometric therapy than MusicGlove training, but the difference was not significant (P>0.09). Subjects sustained improvements in hand function at a one month follow-up, and found the MusicGlove more motivating than the other two therapies, as measured by the IMI. MusicGlove games scores correlated strongly with the B & B score. Conclusions These results support the hypothesis that hand therapy that is engaging, incorporates high numbers of repetitions of gripping and thumb-finger opposition movements, and promotes afferent input is a promising approach to improving an individual’s ability to manipulate small objects. The MusicGlove provides a simple way to access such therapy. PMID:24885076

  1. Retraining and assessing hand movement after stroke using the MusicGlove: comparison with conventional hand therapy and isometric grip training.

    PubMed

    Friedman, Nizan; Chan, Vicky; Reinkensmeyer, Andrea N; Beroukhim, Ariel; Zambrano, Gregory J; Bachman, Mark; Reinkensmeyer, David J

    2014-04-30

    It is thought that therapy should be functional, be highly repetitive, and promote afferent input to best stimulate hand motor recovery after stroke, yet patients struggle to access such therapy. We developed the MusicGlove, an instrumented glove that requires the user to practice gripping-like movements and thumb-finger opposition to play a highly engaging, music-based, video game. The purpose of this study was to 1) compare the effect of training with MusicGlove to conventional hand therapy 2) determine if MusicGlove training was more effective than a matched form of isometric hand movement training; and 3) determine if MusicGlove game scores predict clinical outcomes. 12 chronic stroke survivors with moderate hemiparesis were randomly assigned to receive MusicGlove, isometric, and conventional hand therapy in a within-subjects design. Each subject participated in six one-hour treatment sessions three times per week for two weeks, for each training type, for a total of 18 treatment sessions. A blinded rater assessed hand impairment before and after each training type and at one-month follow-up including the Box and Blocks (B & B) test as the primary outcome measure. Subjects also completed the Intrinsic Motivation Inventory (IMI). Subjects improved hand function related to grasping small objects more after MusicGlove compared to conventional training, as measured by the B & B score (improvement of 3.21±3.82 vs. -0.29±2.27 blocks; P=0.010) and the 9 Hole Peg test (improvement of 2.14±2.98 vs. -0.85±1.29 pegs/minute; P=0.005). There was no significant difference between training types in the broader assessment batteries of hand function. Subjects benefited less from isometric therapy than MusicGlove training, but the difference was not significant (P>0.09). Subjects sustained improvements in hand function at a one month follow-up, and found the MusicGlove more motivating than the other two therapies, as measured by the IMI. MusicGlove games scores correlated strongly with the B & B score. These results support the hypothesis that hand therapy that is engaging, incorporates high numbers of repetitions of gripping and thumb-finger opposition movements, and promotes afferent input is a promising approach to improving an individual's ability to manipulate small objects. The MusicGlove provides a simple way to access such therapy.

  2. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    PubMed

    Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.

  3. Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study

    PubMed Central

    Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M.; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E.; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P.

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy. PMID:23533575

  4. Failure Prediction in Fiber Metal Laminates for Next Generation Aero Materials

    NASA Astrophysics Data System (ADS)

    Jeevan Rao, H.; Janaki Ramulu, Perumalla; Vishnu Vardhan, M.; Chandramouli, CH

    2016-09-01

    In aerospace industry, there is huge demand for low density and low cost materials with better mechanical properties. In this view, there are many researchers developed new materials interms of composites. Similar manner, the present paper also aimed to produce a new approach for cost effective materials of 3D weaved glass fiber metal laminates (FML) with different compositions using a numerical study. A method for the simulation of progressive delamination based on de-cohesion elements has been presented. De-cohesion elements are placed between layers of solid elements that open and shear in response to the loading situation. The onset of damage and the growth of delamination are simulated without previous knowledge about the location, the size, or the direction of propagation of the de-laminations. A softening law for mixed-mode delamination that can be applied to any interaction criterion is also proposed. The constitutive equation proposed uses a single variable, the maximum relative displacement, to track the damage at the interface under general loading conditions. The material properties required to define the element constitutive equation are the inter-laminar fracture toughness's, the penalty stiffness, and the strengths.

  5. Differents aspects du fer dans l'organisme

    PubMed Central

    Bessis, Marcel; Breton-Gorius, Janine

    1959-01-01

    On voit des molécules de ferritine apparaitre dans le cytoplasme des cellules réticulaires au cours de la digestion des érythrocytes, autour des stromas phagocytés. Cette ferritine s'accumule en amas dans lesquels entrent d'autres substances, en particulier des lipides, provenant aussi des stromas globulaires et qui apparaissent sous forme myélinique. Souvent la ferritine se dispose d'une manière cristalline. Parfois la ferritine et l'apoferritine alternent dans ces cristaux. Parfois l'hémosidérine contient des cristaux qui semblent bien être de l'apoferritine pure. L'injection de sels de fer donne lieu à l'apparition de ferritine dans les cellules réticulaires. Dans les conditions de nos expériences, la plus grande partie du fer injecté était sous forme de ferritine dans un délai de 3 jours. Un aspect intermédiaire entre celui du fer injecté et celui de la ferritine a été trouvé. Dans le cas des injections de saccharate de fer ce sont de fines aiguilles; dans le cas des injections de lactate de fer, il s'agit de masses fibreuses. PMID:13800106

  6. The GuideLine Interchange Format

    PubMed Central

    Ohno-Machado, Lucila; Gennari, John H.; Murphy, Shawn N.; Jain, Nilesh L.; Tu, Samson W.; Oliver, Diane E.; Pattison-Gordon, Edward; Greenes, Robert A.; Shortliffe, Edward H.; Barnett, G. Octo

    1998-01-01

    Objective: To allow exchange of clinical practice guidelines among institutions and computer-based applications. Design: The GuideLine Interchange Format (GLIF) specification consists of the GLIF model and the GLIF syntax. The GLIF model is an object-oriented representation that consists of a set of classes for guideline entities, attributes for those classes, and data types for the attribute values. The GLIF syntax specifies the format of the test file that contains the encoding. Methods: Researchers from the InterMed Collaboratory at Columbia University, Harvard University (Brigham and Women's Hospital and Massachusetts General Hospital), and Stanford University analyzed four existing guideline systems to derive a set of requirements for guideline representation. The GLIF specification is a consensus representation developed through a brainstorming process. Four clinical guidelines were encoded in GLIF to assess its expressivity and to study the variability that occurs when two people from different sites encode the same guideline. Results: The encoders reported that GLIF was adequately expressive. A comparison of the encodings revealed substantial variability. Conclusion: GLIF was sufficient to model the guidelines for the four conditions that were examined. GLIF needs improvement in standard representation of medical concepts, criterion logic, temporal information, and uncertainty. PMID:9670133

  7. Consensus canadien sur la contraception (3(e) partie de 4) : chapitre 8 - contraception à progestatif seul.

    PubMed

    Black, Amanda; Guilbert, Edith; Costescu, Dustin; Dunn, Sheila; Fisher, William; Kives, Sari; Mirosh, Melissa; Norman, Wendy V; Pymar, Helen; Reid, Robert; Roy, Geneviève; Varto, Hannah; Waddington, Ashley; Wagner, Marie-Soleil; Whelan, Anne Marie

    2016-03-01

    Fournir des lignes directrices aux fournisseurs de soins quant à l'utilisation de modes de contraception pour la prévention de la grossesse et quant à la promotion d'une sexualité saine. Orientation des praticiens canadiens en ce qui concerne l'efficacité globale, le mécanisme d'action, les indications, les contre-indications, les avantages n'étant pas liés à la contraception, les effets indésirables, les risques et le protocole de mise en œuvre des modes de contraception abordés; planification familiale dans le contexte de la santé sexuelle et du bien-être général; méthodes de counseling en matière de contraception; et accessibilité et disponibilité des modes de contraception abordés au Canada. RéSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans MEDLINE et The Cochrane Library entre janvier 1994 et janvier 2015 au moyen d'un vocabulaire contrôlé (p. ex. contraception, sexuality, sexual health) et de mots clés (p. ex. contraception, family planning, hormonal contraception, emergency contraception) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre janvier 1994 et janvier 2015. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en juin 2015. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. La qualité des résultats a été évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). CHAPITRE 8 : CONTRACEPTION à PROGESTATIF SEUL: Déclarations sommaires Recommandations. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

  8. Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project.

    PubMed

    de Hoogt, Ronald; Estrada, Marta F; Vidic, Suzana; Davies, Emma J; Osswald, Annika; Barbier, Michael; Santo, Vítor E; Gjerde, Kjersti; van Zoggel, Hanneke J A A; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M; Verschuren, Emmy W; Hickman, John; Graeser, Ralph

    2017-11-21

    Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented.

  9. Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project

    PubMed Central

    de Hoogt, Ronald; Estrada, Marta F.; Vidic, Suzana; Davies, Emma J.; Osswald, Annika; Barbier, Michael; Santo, Vítor E.; Gjerde, Kjersti; van Zoggel, Hanneke J. A. A.; Blom, Sami; Dong, Meng; Närhi, Katja; Boghaert, Erwin; Brito, Catarina; Chong, Yolanda; Sommergruber, Wolfgang; van der Kuip, Heiko; van Weerden, Wytske M.; Verschuren, Emmy W.; Hickman, John; Graeser, Ralph

    2017-01-01

    Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono- and stromal co-cultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented. PMID:29160867

  10. α-Conotoxin Decontamination Protocol Evaluation: What Works and What Doesn’t

    PubMed Central

    Turner, Matthew W.; Cort, John R.; McDougal, Owen M.

    2017-01-01

    Nine publically available biosafety protocols for safely handling conotoxin peptides were tested to evaluate their decontamination efficacy. Circular dichroism (CD) spectroscopy and mass spectrometry (MS) were used to assess the effect of each chemical treatment on the secondary and primary structure of α-CTx MII (L10V, E11A). Of the nine decontamination methods tested, treatment with 1% (m/v) solution of the enzymatic detergent Contrex™ EZ resulted in a 76.8% decrease in α-helical content as assessed by the mean residue ellipticity at 222 nm, and partial peptide digestion was demonstrated using high performance liquid chromatography mass spectrometry (HPLC-MS). Additionally, treatment with 6% sodium hypochlorite (m/v) resulted in 80.5% decrease in α-helical content and complete digestion of the peptide. The Contrex™ EZ treatment was repeated with three additional α-conotoxins (α-CTxs), α-CTxs LvIA, ImI and PeIA, which verified the decontamination method was reasonably robust. These results support the use of either 1% Contrex™ EZ solution or 6% sodium hypochlorite in biosafety protocols for the decontamination of α-CTxs in research laboratories. PMID:28906461

  11. Safety of Pochonia chlamydosporia var catenulata in acute oral and dermal toxicity/pathogenicity evaluations in rats and rabbits.

    PubMed

    García, Liseth; Bulnes, Carlos; Melchor, Gleiby; Vega, Ernesto; Ileana, Miranda; de Oca, Nivian Montes; Hidalgo, Leopoldo; Marrero, Eva

    2004-10-01

    The nematophagous fungus, Pochonia chlamydosporia var. catenulata (Kamyschlco ex Barron & Onions) Zare & W-Gams, was investigated as a potential biocontrol agent in integrated pest management strategy for Meloidogyne incognita (Kofoid and White) Chitwood in vegetable crops in Cuba. An acute oral and dermal toxicity/patogenicity study was performed to determine the safety of this fungus in non-target organisms. In the first study, a 1-dose level of 5 x 10(8) units of the microbial pest control agent/treated rat was used. Mortality or clinical signs were not evident and no adverse effects on body weight, hematology, microbiology and gross or microscopic pathology were observed. Food and water consumption was not significantly different between control and treated groups. In the acute dermal toxicity study, there was neither mortality nor clinical signs of toxicity, and no toxic effects in gross and microscopic pathology were detected. Thus, Pochonia chlamydosporia var. catenulate (Vcc-108, IMI SD 187), administered oral and dermally to rats and rabbits respectively, was safe in toxicity/pathogenicity studies.

  12. The effect of a cannula milk sampling technique on the microbiological diagnosis of bovine mastitis.

    PubMed

    Friman, M; Hiitiö, H; Niemi, M; Holopainen, J; Pyörälä, S; Simojoki, H

    2017-08-01

    Two methods of collecting milk samples from mastitic bovine mammary quarters were compared. Samples were taken in a consistent order in which standard aseptic technique sampling was done first, followed by insertion of a sterile cannula through the teat canal and collection of a second sample. Microbiological results of those two sampling techniques were compared. Milk samples were analysed using multiplex real-time polymerase chain reaction (PCR). The cannula technique produced a reduced number of microbial species or groups of species per sample compared with conventional sampling. Staphylococcus spp. were the most common species identified and were detected more often during conventional sampling than with cannula sampling. Staphylococcus spp. identified in milk samples could also have originated from the teat canal without being present in the milk. The number of samples positive for Trueperella pyogenes or yeasts in the conventional samples was twice as high as in the cannula samples, indicating that the presence of Trueperella pyogenes and yeast species should not necessarily be interpreted as being the causative agents of bovine intra-mammary infections (IMI). Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. α-Conotoxin dendrimers have enhanced potency and selectivity for homomeric nicotinic acetylcholine receptors.

    PubMed

    Wan, Jingjing; Huang, Johnny X; Vetter, Irina; Mobli, Mehdi; Lawson, Joshua; Tae, Han-Shen; Abraham, Nikita; Paul, Blessy; Cooper, Matthew A; Adams, David J; Lewis, Richard J; Alewood, Paul F

    2015-03-11

    Covalently attached peptide dendrimers can enhance binding affinity and functional activity. Homogenous di- and tetravalent dendrimers incorporating the α7-nicotinic receptor blocker α-conotoxin ImI (α-ImI) with polyethylene glycol spacers were designed and synthesized via a copper-catalyzed azide-alkyne cycloaddition of azide-modified α-ImI to an alkyne-modified polylysine dendron. NMR and CD structural analysis confirmed that each α-ImI moiety in the dendrimers had the same 3D structure as native α-ImI. The binding of the α-ImI dendrimers to binding protein Ac-AChBP was measured by surface plasmon resonance and revealed enhanced affinity. Quantitative electrophysiology showed that α-ImI dendrimers had ∼100-fold enhanced potency at hα7 nAChRs (IC50 = 4 nM) compared to native α-ImI (IC50 = 440 nM). In contrast, no significant potency enhancement was observed at heteromeric hα3β2 and hα9α10 nAChRs. These findings indicate that multimeric ligands can significantly enhance conotoxin potency and selectivity at homomeric nicotinic ion channels.

  14. Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

    PubMed

    Majiduddin, Fahd K; Palzkill, Timothy

    2003-03-01

    Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

  15. Amino Acid Sequence Requirements at Residues 69 and 238 for the SME-1 β-Lactamase To Confer Resistance to β-Lactam Antibiotics

    PubMed Central

    Majiduddin, Fahd K.; Palzkill, Timothy

    2003-01-01

    Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring β-lactamases and extended-spectrum β-lactamases. Four enzymes from the class A group of β-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these β-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of β-lactam antibiotics. PMID:12604542

  16. A sensitivity-enhanced refractive index sensor using a single-mode thin-core fiber incorporating an abrupt taper.

    PubMed

    Shi, Jie; Xiao, Shilin; Yi, Lilin; Bi, Meihua

    2012-01-01

    A sensitivity-enhanced fiber-optic refractive index (RI) sensor based on a tapered single-mode thin-core diameter fiber is proposed and experimentally demonstrated. The sensor head is formed by splicing a section of tapered thin-core diameter fiber (TCF) between two sections of single-mode fibers (SMFs). The cladding modes are excited at the first SMF-TCF interface, and then interfere with the core mode at the second interface, thus forming an inter-modal interferometer (IMI). An abrupt taper (tens of micrometers long) made by the electric-arc-heating method is utilized, and plays an important role in improving sensing sensitivity. The whole manufacture process only involves fiber splicing and tapering, and all the fabrication process can be achieved by a commercial fiber fusion splicer. Using glycerol and water mixture solution as an example, the experimental results show that the refractive index sensitivity is measured to be 0.591 nm for 1% change of surrounding RI. The proposed sensor structure features simple structure, low cost, easy fabrication, and high sensitivity.

  17. Qualification of imaging biomarkers for oncology drug development.

    PubMed

    Waterton, John C; Pylkkanen, Liisa

    2012-03-01

    Although many imaging biomarkers have been described for cancer research, few are sufficiently robust, reliable and well-characterised to be used as routine tools in clinical cancer research. In particular, biomarkers which show that investigational therapies have reduced tumour cell proliferation, or induced necrotic or apoptotic cell death are not commonly used to support decision-making in drug development, even though such pharmacodynamic effects are common goals of many classes of investigational drugs. Moreover we lack well-qualified biomarkers of propensity to metastasise. The qualification and technical validation of imaging biomarkers poses unique challenges not always encountered when validating biospecimen biomarkers. These include standardisation of acquisition and analysis, imaging-pathology correlation, cross-sectional clinical-biomarker correlations and correlation with outcome. Such work is ideally suited to precompetitive research and public-private partnerships, and this has been recognised within the Innovative Medicines Initiative (IMI), a Joint Undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations, which has initiated projects in the areas of drug safety, drug efficacy, knowledge management and training. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Caracterisation des signatures de decharges partielles en utilisant une nouvelle generation de coupleurs piezoelectriques

    NASA Astrophysics Data System (ADS)

    Danouj, Boujemaa

    An important issue affecting the sustainability of power transformers is systematic and progressive deterioration of the insulation system by the action of partial discharge. Ideally, it is appropriate to use on line, non-destructive techniques for detection and diagnosis of failures related to insulation systems, in order to determine whether preventive maintenance action is required. Thus, huge material losses can be saved (spared), while improving reliability and system availability. Based on a new generation of piezoelectric sensors (High Temperature Ultrasonic Transducers HTUTs), recently developed by the Industrial Materials Institute (IMI) in Boucherville (Qc, Canada) and offers very interesting features (broad band frequency response, flexible, miniature, economic, etc..), we propose in this thesis an investigation on the applicability of this technology to the problematic of partial discharges. This work presents an analysis of the metrological performance of these sensors and demonstrated empirically the consistency of their measures. It outlines the results of validation from a comparative study with the measures of a standard detection circuit. In addition, it also presents the potential of these sensors to locate partial discharge source position by acoustic emission.

  19. Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition to Support Model‐Informed Drug Discovery and Development

    PubMed Central

    Wilkins, JJ; Chan, PLS; Chard, J; Smith, G; Smith, MK; Beer, M; Dunn, A; Flandorfer, C; Franklin, C; Gomeni, R; Harnisch, L; Kaye, R; Moodie, S; Sardu, ML; Wang, E; Watson, E; Wolstencroft, K

    2017-01-01

    Pharmacometric analyses are complex and multifactorial. It is essential to check, track, and document the vast amounts of data and metadata that are generated during these analyses (and the relationships between them) in order to comply with regulations, support quality control, auditing, and reporting. It is, however, challenging, tedious, error‐prone, and time‐consuming, and diverts pharmacometricians from the more useful business of doing science. Automating this process would save time, reduce transcriptional errors, support the retention and transfer of knowledge, encourage good practice, and help ensure that pharmacometric analyses appropriately impact decisions. The ability to document, communicate, and reconstruct a complete pharmacometric analysis using an open standard would have considerable benefits. In this article, the Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe) consortium proposes a set of standards to facilitate the capture, storage, and reporting of knowledge (including assumptions and decisions) in the context of model‐informed drug discovery and development (MID3), as well as to support reproducibility: “Thoughtflow.” A prototype software implementation is provided. PMID:28504472

  20. The IMI PROTECT project: purpose, organizational structure, and procedures.

    PubMed

    Reynolds, Robert F; Kurz, Xavier; de Groot, Mark C H; Schlienger, Raymond G; Grimaldi-Bensouda, Lamiae; Tcherny-Lessenot, Stephanie; Klungel, Olaf H

    2016-03-01

    The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug-adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug-adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally. Copyright © 2016 John Wiley & Sons, Ltd.

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