Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

Fate of the herbicide glyphosate and its metabolite AMPA in soils and their transfer to surface waters: A multi-scale approach in the Lavaux vineyards, western Switzerland

The use of herbicides in agriculture may lead to environmental problems, such as surface water pollution, with a potential risk for aquatic organisms. The herbicide glyphosate is the most used active ingredient in the world and in Switzerland. In the Lavaux vineyards it is nearly the only molecule applied. This work aimed at studying its fate in soils and its transfer to surface waters, using a multi-scale approach: from molecular (10-9 m) and microscopic scales (10-6 m), to macroscopic (m) and landscape ones (103 m). First of all, an analytical method was developed for the trace level quantification of this widely used herbicide and its main by-product, aminomethylphosphonic acid (AMPA). Due to their polar nature, their derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) was done prior to their concentration and purification by solid phase extraction. They were then analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method was tested in different aqueous matrices with spiking tests and validated for the matrix effect correction in relevant environmental samples. Calibration curves established between 10 and 1000ng/l showed r2 values above 0.989, mean recoveries varied between 86 and 133% and limits of detection and quantification of the method were as low as 5 and 10ng/l respectively. At the parcel scale, two parcels of the Lavaux vineyard area, located near the Lutrive River at 6km to the east of Lausanne, were monitored to assess to which extent glyphosate and AMPA were retained in the soil or exported to surface waters. They were equipped at their bottom with porous ceramic cups and runoff collectors, which allowed retrieving water samples for the growing seasons 2010 and 2011. Results revealed that the mobility of glyphosate and AMPA in the unsaturated zone was likely driven by the precipitation regime and the soil characteristics, such as slope, porosity structure and layer permeability discrepancy. Elevated glyphosate and AMPA concentrations were measured at 60 and 80 cm depth at parcel bottoms, suggesting their infiltration in the upper parts of the parcels and the presence of preferential flow in the studied parcels. Indeed, the succession of rainy days induced the gradual saturation of the soil porosity, leading to rapid infiltration through macropores, as well as surface runoff formation. Furthermore, the presence of more impervious weathered marls at 100 cm depth induced throughflows, the importance of which for the lateral transport of the herbicide molecules was determined by the slope steepness. Important rainfall events (>10 mm/day) were clearly exporting molecules from the soil top layer, as indicated by important concentrations in runoff samples. A mass balance showed that total loss (10-20%) mainly occurred through surface runoff (96%) and, to a minor extent, by throughflows in soils (4%), with subsequent exfiltration to surface waters. Observations made in the Lutrive River revealed interesting details of glyphosate and AMPA dynamics in urbanized landscapes, such as the Lavaux vineyards. Indeed, besides their physical and chemical properties, herbicide dynamics at the catchment level strongly depend on application rates, precipitation regime, land use and also on the presence of drains or constructed channels. Elevated concentrations, up to 4970 ng/l, observed just after the application, confirmed the diffuse export of these compounds from the vineyard area by surface runoff during main rain events. From April to September 2011, a total load of 7.1 kg was calculated, with 85% coming from vineyards and minor urban sources and 15% from arable crops. Small vineyard surfaces could generate high concentrations of herbicides and contribute considerably to the total load calculated at the outlet, due to their steep slopes (~10%). The extrapolated total amount transferred yearly from the Lavaux vineyards to the Lake of Geneva was of 190kg. At the molecular scale, the possible involvement of dissolved organic matter (DOM) in glyphosate and copper transport was studied using UV/Vis fluorescence spectroscopy. Combined with parallel factor (PARAFAC) analysis, this technique allowed characterizing DOM of soil and surface water samples from the studied vineyard area. Glyphosate concentrations were linked to the fulvic-like spectroscopic signature of DOM in soil water samples, as well as to copper, suggesting the formation of ternary complexes. In surface water samples, its concentrations were also correlated to copper ones, but not in a significant way to the fulvic-like signature. Quenching experiments with standards confirmed field tendencies in the laboratory, with a stronger decrease in fluorescence intensity for fulvic-like fluorophore than for more aromatic ones. Lastly, based on maximum concentrations measured in the river, an environmental risk for these compounds was assessed, using laboratory tests and ecotoxicity data from the literature. In our case and with the methodology applied, the risk towards aquatic species was found negligible (RF<1).

Soybean cultivar BR-16-AHAS tolerance to the herbicide imazapyr

The objective of this work was to evaluate the effect of the transgenic soybean BR-16-AHAS genetic constitution on the tolerance to the herbicide imazapyr. BR-16-AHAS was crossed with ten other genotypes. The experimental design was a complete randomized block, in a 2x12x3 factorial arrangement, with two sowing periods (winter and summer), twelve crossing groups and three plant positions (upper, mid and lower), with three replicates. The plants were treated with 100 g ha-1 a.i. of imazapyr at the V3/V4 stage. For each position of the plant (upper, mid and lower), the following variables were assessed: number of pods, number of seeds, seed weight, number of seeds per pod and the 100 seeds weight. The effect of the herbicide varied according to the more affected plant position (upper, mid and lower) of each genotype. The use of the same gene ahas of BR-16-AHAS, in various genotypes, results in materials with good tolerance to imazapyr; tolerance levels depend not only on the ahas gene, but also on the presence of other genes.

Development of herbicide-tolerant irrigated rice cultivars

The objective of this work was to develop new irrigated rice lines tolerant to imidazolinone herbicides. The backcross breeding procedure was used to transfer the imidazolinone tolerance allele from mutant 93AS3510 to the recurrent parents 'BRS 7 Taim' and 'BRS Pelota'. Individual herbicide-tolerant plants were selected in each generation, for three backcrossings (RC1 to RC3), followed by three selfing generations (RC3F1 to RC3F3). The best four RC3F3 lines for agronomic traits were genotyped with 44 microsatellite markers. The observed conversion index of the new imidazolinone-tolerant lines varied from 91.86 to 97.67%. Pairwise genetic distance analysis between these lines and 22 accessions from the Embrapa's Rice Germplasm Bank clustered the new lines with their respective recurrent parents, but not with 'IRGA 417', which was originally used as recurrent parent to derive IRGA 422 CL, the only imidazolinone-tolerant irrigated rice cultivar recommended for cultivation in Brazil. Therefore, these lines represent new options of genetically diverse imidazolinone-tolerant rice accessions. Lines CNA10756 ('BRS Sinuelo CL') and CNA10757 will be released for cultivation in the Clearfield irrigated rice production system in Rio Grande do Sul, Brazil.

Cover crops and herbicide timing management on soybean yield under no-tillage system

The objective of this work was to evaluate the effect of cover crops and timing of pre-emergence herbicide applications on soybean yield under no-tillage system. The experiment consisted of four cover crops (Panicum maximum, Urochloa ruziziensis, U. brizantha, and pearl millet) and fallow, in addition to four herbicide timings (30, 20, 10, and 0 days before soybean sowing), under no-tillage system (NTS), and of two control treatments under conventional tillage system (CTS). The experimental design was a completely randomized block, in a split-plot arrangement, with three replicates. Soybean under fallow, P. maximum, U. ruziziensis, U. brizantha, and pearl millet in the NTS and soybean under U. brizantha in the CTS did not differ significantly regarding yield. Soybean under fallow in the CTS significantly reduced yield when compared to the other treatments. The amount of straw on soil surface did not significantly affect soybean yield. Chemical management of P. maximum and U. brizantha near the soybean sowing date causes significant damage in soybean yield. However, herbicide timing in fallow, U. ruziziensis, and pearl millet does not affect soybean yield.

Information retention during competitive interactions : siblings need to constantly repeat vocal displays

Memory is essential to adjust behaviour according to past experience. In societies where animals interact on numerous occasions, memory of previous social interactions may help optimise investment in competition. How long information about the resource holding potential and motivation to compete of conspecifics is retained depends on how fast the value of this information fades, but also on the cost and benefit of retaining information. Information retention has never been investigated in the context of interactions prevailing within the family and more specifically sibling competition. In the absence of parents, barn owl (Tyto alba) nestlings vocally compete for priority of access to the next indivisible food item brought by a parent. The finding that owlets eavesdrop on vocal interactions between siblings to adjust investment in vocalization once competing with them suggests that they memorize siblings' vocal interactions. Playback experiments showed that owlets take into account the past siblings' vocal performance that signals hunger for at least 15 min, but only if the performance was witnessed during a sufficiently long period of time (30 min). Moreover, using natural vocal exchanges in another set of individuals, we showed that sibling signalling was no more taken into account after a few minutes. This suggests that young barn owls need to continuously display their motivation to trigger siblings' withdrawal from the current competition. Repeating a vocal display may ensure its honesty. Studying the extent to which individuals retain past information is important to understand how individuals adjust their competitive investment over resources.

Separation mechanisms in nanofiltration and retention changes of organic compounds

Orgaanisten yhdisteiden negatiivinen retentio nanosuodatuksessa on ilmiö, jota eiole kovin paljon tutkittu. Negatiivisen retentioon vaikuttavat syyt tai tekijäteivät ole kovin hyvin tiedossa. Erotusmenetelmänä negatiivinen retentio voi olla käyttökelpoinen tietyissä sovelluksissa. Työn kirjallisuusosa käsittelee nanosuodatuksen erotusmekanismeja ja retentioon vaikuttavia tekijöitä. Myös joitakin malleja on esitetty. Nanosuodatus on monimutkainen prosessi, josta ei voida löytää vain yhtä erotusmekanismia tai retentioon vaikuttavaa tekijää. Prosessit ovat kokonaisuuksia, joissa erottumiseen vaikuttavat syöttöliuoksen, erotettavan komponentin ja kalvon ominaisuudet, ja niiden väliset vuorovaikutukset. Työn kokeellisessa osassa koottiin mahdollisimman paljon esimerkkejä, joissa monosakkaridien negatiivinen retentio ilmenee. Muita orgaanisia ja epäorgaanisia yhdisteitä käytettiin 'häiriöyhdisteinä' syöttöliuoksessa monosakkaridien kanssa. Kokeet suoritettiin kahdella laboratoriomittakaavan suodatuslaitteella käyttäen kahta kaupallista nanosuodatuskalvoa. Negatiivinen retentio ilmeni useissa tapauksissa. Permeaattivuon ja 'häiriöyhdisteiden' pitoisuuksien havaittiin vaikuttavan voimakkaasti negatiivisen retention ilmenemiseen.

Effect of physico-chemical conditions and operating parameters on flux and retention of different components in ultrafiltration and nanofiltration fractionation of sweet whey

Tässä väitöstutkimuksessa tutkittiin fysikaaliskemiallisten olosuhteiden ja toimintaparametrien vaikutusta juustoheran fraktiointiin. Kirjallisuusosassa on käsitelty heran ympäristövaikutusta, heran hyödyntämistä ja heran käsittelyä kalvotekniikalla. Kokeellinen osa on jaettu kahteen osaan, joista ensimmäinen käsittelee ultrasuodatusta ja toinen nanosuodatusta juustoheran fraktioinnissa. Ultrasuodatuskalvon valinta tehtiin perustuen kalvon cut-off lukuun, joka oli määritetty polyetyleeniglykoliliuoksilla olosuhteissa, joissa konsentraatiopolariosaatioei häiritse mittausta. Kriittisen vuon konseptia käytettiin sopivan proteiinikonsentraation löytämiseksi ultrasuodatuskokeisiin, koska heraproteiinit ovat tunnetusti kalvoa likaavia aineita. Ultrasuodatuskokeissa tutkittiin heran eri komponenttien suodattumista kalvon läpi ja siihen vaikuttavia ominaisuuksia. Herapermeaattien peptidifraktiot analysoitiin kokoekskluusiokromatografialla ja MALDI-TOF massaspektrometrillä. Kokeissa käytettävien nanosuodatuskalvojen keskimääräinen huokoskoko analysoitiin neutraaleilla liukoisilla aineilla ja zeta-potentiaalit virtauspotentiaalimittauksilla. Aminohappoja käytettiin malliaineina tutkittaessa huokoskoon ja varauksen merkitystä erotuksessa. Aminohappojen retentioon vaikuttivat pH ja liuoksen ionivahvuus sekä molekyylien väliset vuorovaikutukset. Heran ultrasuodatuksessa tuotettu permeaatti, joka sisälsi pieniä peptidejä, laktoosia ja suoloja, nanosuodatettiin happamassa ja emäksisessä pH:ssa. Emäksisissä oloissa tehdyssä nanosuodatuksessa foulaantumista tapahtui vähemmän ja permeaattivuo oli parempi. Emäksisissä oloissa myös selektiivisyys laktoosin erotuksessa peptideistä oli parempi verrattuna selektiivisyyteen happamissa oloissa.

A germination study of herbicide-resistant field poppies in Spain

Field poppy, Papaver rhoeas L., is a very common weed in winter cereals in North-Eastern Spain. Its control is becoming difficult due to expanding herbicide resistance. To control field poppies there are alternative strategies such as non-chemical control that take into account the weed emergence period. However, there is a lack of knowledge of P. rhoeas emergence patterns in semi-arid conditions. Thus, here we conducted pot experiments on the emergence of P. rhoeas. We aimed to describe the emergence period and to quantify the emergence of a susceptible and of a herbicide-resistant P. rhoeas population at two locations in Catalonia, Spain, from 1998 to 2001 and until 2004 at one of them. Therefore, pots containing seeds of both populations were established at the two locations and emergence was recorded monthly. We studied the origin of the population, the sowing location, the effect of cultivation and the sowing year. First, we found that the main emergence peaks in our experiments occurred in autumn, accounting for between 65.7 and 98.5% of the annual emergence from October to December, and only little emergence was recorded in spring. This emergence pattern is different from those found in the literature corresponding to Northern European countries, where in some cases main flushes occur only in autumn, in spring and winter or only in spring. The emergence was mainly affected by cultivation, but the effect of light stimulus was observed several months later. As a consequence, cultivation should be done in early autumn, promoting emergence during the whole autumn and winter so that emerged seedlings can be controlled before sowing a spring crop. Second, most experiments showed that the emergence was significantly higher in the first autumn than in the following seasons, e.g. 4.1% emergence in the first year and only 2.1, 2.3, 0.5 and 0.6% new emergence at one of the locations for the second, third, fourth and fifth years. Thus, after having a severe P. rhoeas infestation causing a big seed rain, emergence should be stimulated by autumn cultivation in the following season and seedlings controlled by trying to deplete the soil seed bank as much as possible. Despite the fact that emergence will be staggered throughout several years and that there was a significant relationship between rainfall and emergence, so that dry years will cause a smaller emergence rate of the weed, these findings define a cultural management strategy to reduce P. rhoeas infestations and to contribute to integrated weed management strategies combining it with other tools.

Cultural control of herbicide-resistant Lolium rigidum Gaud. populations in winter cereal in Northeastern Spain

Lolium rigidum Gaud. is one of the most common weed species in winter cereals in Northeastern Spain. Herbicide resistance has been growing since the mid 90's and exclusive herbicide use is not enough in many cases, so that it is necessary to combine as many control tools as possible. Six field trials have been conducted during the cropping seasons 2001-02, 2002-03 and 2003-04 on winter cereal infested with herbicide resistant L. rigidum in Northeastern Spain testing different cultural control strategies. Sowing delay was conducted at five fields, mouldboard ploughing at four fields, the combination of sowing delay and ploughing at two fields, increasing the cereal sowing density and combined with sowing delay at one field. Sowing delay was confirmed to have an irregular efficacy depending on the L. rigidum emergence during the delay period. In the trials, weed emergence was reduced up to 88% in the best case but there was no effect in two cases. Ploughing had a more constant efficacy and reduced weed emergence between 50 and 80% although stoniness impeded in one occasion a correct soil inversion causing a very low efficacy. Increasing the cereal sowing rate did not reduce the weed population. The combination of the different methods did not increase significantly the individual efficacy, and one method was clearly more effective than the other, depending on the trial. In fields with high L. rigidum density, these methods are not effective enough and need to be combined with other methods, which are discussed in the text.

Customer Retention in a Health Club

The objective of this study was to resolve how a privately owned health club can retain their existing customers. It was also resolved why there is a need for customer retention in general, and what the constructs leading to retention are. In addition, the relationship between customer satisfaction and customer retention was studied and discussed.

Growth, production and quality of pineapple in response to herbicide use

In pineapple fields, weed competition is exacerbated by the fact that the crop is small and has a very slow vegetative development. The objective of this study was to determine the effects of herbicides on growth, yield and quality of pineapple, cultivar 'Pérola'. The experimental design was in randomized blocks with four treatments and four replications. Treatments consisted of weeding by hoe and the herbicides diuron; fluazifop-p-butyl and atrazine + S-metolachlor applied in post-emergence. The characteristics evaluated monthly during the vegetative stage were stem diameter, D-leaf length, number of leaves, number of emitted leaves and percentage of natural floral induction. In the reproductive phase, evaluations were made of average fruit weight (g) with and without crown, fruits length and diameter, number of slip, slip-sucker and sucker type seedlings, determination of soluble solids and pH in the pulp. There was no effect of herbicide treatment on the vegetative growth characteristics. Stem diameter increased until 330 days after planting, showing a decrease after this period. The D-leaf grew over time in all treatments, although phytotoxicity symptoms were observed after the first application of herbicides. The traits evaluated on the reproductive phase showed no significant differences in response to treatments. Therefore, the use of diuron fluazifop-p-butyl and atrazine + S-metolachlor did not affect growth, yield and fruit quality of pineapple, cultivar 'Pérola'.

Characterization and genetic mapping of eceriferum-ym (cer-ym), a cutin deficient barley mutant with impaired leaf water retention capacity.

The cuticle covers the aerial parts of land plants, where it serves many important functions, including water retention. Here, a recessive cuticle mutant, eceriferum-ym (cer-ym), of Hordeum vulgare L. (barley) showed abnormally glossy spikes, sheaths, and leaves. The cer-ym mutant plant detached from its root system was hypersensitive to desiccation treatment compared with wild type plants, and detached leaves of mutant lost 41.8% of their initial weight after 1 h of dehydration under laboratory conditions, while that of the wild type plants lost only 7.1%. Stomata function was not affected by the mutation, but the mutant leaves showed increased cuticular permeability to water, suggesting a defective leaf cuticle, which was confirmed by toluidine blue staining. The mutant leaves showed a substantial reduction in the amounts of the major cutin monomers and a slight increase in the main wax component, suggesting that the enhanced cuticle permeability was a consequence of cutin deficiency. cer-ym was mapped within a 0.8 cM interval between EST marker AK370363 and AK251484, a pericentromeric region on chromosome 4H. The results indicate that the desiccation sensitivity of cer-ym is caused by a defect in leaf cutin, and that cer-ym is located in a chromosome 4H pericentromeric region.

Effects of business-to-business customer orientation, satisfaction and retention on firm profitability

The objective of this master’s thesis was to examine the effect of customer orientation on customer satisfaction and how customer satisfaction and customer retention contribute to firm profitability. Beside customer orientation, also other antecedents of customer satisfaction, i.e. service quality, flexibility, trust and commitment, were investigated as control variables. Literature review revealed several research gaps concerning research of the key concepts. These research calls were also answered. The empirical study focused on one case company, a telecommunication expert. The data for the empirical part was collected with web-based questionnaire from case company’s business customers in January-February 2008. Sample (N=95) produced 59 answers, thus the response rate of the survey was 62,1%. The data was analyzed by using statistical analysis program, SPSS. As a conclusion, the results indicate that customer orientation do not affect customer satisfaction directly, but through service quality, flexibility and trust. Moreover, customer satisfaction has positive impacts on commitment and intentions to stay as a customer in the future, but not on profitability. In the present study, only past purchase behavior, measured with customer database measure, is positively related to firm profitability.

Repeated Whole-Genome Duplication, Karyotype Reshuffling, and Biased Retention of Stress-Responding Genes in Buckler Mustard.

Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the β- and α-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges.