The PAL activity in Wuyujing 3 increased slightly at 12 hpi, significantly increased at 24 hpi, reached its highest value at 36 hpi and then showed a smooth trend of decline. The PAL activity in Kasalath was remarkably higher than in Wuyujing 3 at all of the tested time points in response to SBPH feeding (Table 2). These results indicated PAL activity was induced in both rice accessions by SBPH infestation

but the rate and magnitude of increase in activity was significantly higher in Kasalath than in Wuyujing 3. SBPH feeding resulted at first in a gradual increase and then a decrease in PPO activity in the two rice varieties. However, PPO activity FK228 in vitro in Kasalath was significantly higher at 24 hpi than at 0 hpi. This activity reached a peak at 36 hpi

and then decreased slightly. Changes in PPO activity in Wuyujing 3 were small after SBPH feeding. There was no significant difference in PPO activity between any of the time points (Table 2). PPO activity in Kasalath was higher than in Wuyujing 3 at all of the time points tested. For the second enzyme, POD, activity rose significantly in both Kasalath and Wuyujing 3 when infested Selleckchem Ruxolitinib by SBPH but the rate and magnitude of increase in Kasalath was far greater than in Wuyujing 3. There was no distinct difference in POD activity between Kasalath and Wuyujing 3 before SBPH attack. POD activity increased quickly and maintained an increasing trend in both genotypes when attacked by SBPH. Significant differences in POD activity were detected between every pair of time points (Table 2). The activity

of POD in Kasalath was higher than in Wuyujing 3 at every time point after SBPH feeding, indicating that POD accumulation was remarkably responsive and sensitive to SBPH infestation. The expression level of the PAL gene was closely related to the activities of the defense enzymes PAL, POD and PPO in the resistant variety of rice, Kasalath, with high correlation coefficients Mannose-binding protein-associated serine protease (r) of 0.9051, 0.8687 and 0.7504, respectively. Similarly, there was positive correlation between EDS1 gene expression levels and PAL, POD and PPO enzyme activities in Kasalath, with r values of 0.5887, 0.7738 and 0.3248, respectively. However, there was no relationship between the PAL expression level and the enzyme activities of PAL, POD and PPO in the susceptible Wuyujing 3 rice (r = − 0.0662, − 0.1682 and − 0.1492, respectively). In addition, there was a close correlation between POD enzyme activity and the expression levels of the AOS2, EIN2 and LOX genes in Wuyujing 3 (r = 0.8688, 0.7980 and 0.6368, respectively).

Therefore, in this study we used axenic strains of P. donghaiense and P. tricornutum to assess their allelopathic interactions under controlled laboratory conditions. We first investigated their mutual interactions in a laboratory-designed co-culture experiment with several combinations of initial cell densities. Then, we further tested the allelopathic effects of the cell-free filtrates of one species on the growth of the other one by growing the microalgal cells in the presence of enriched culture filtrates. Both the axenic strains of the dinoflagellate

Prorocentrum Verteporfin clinical trial donghaiense Lu and the marine diatom Phaeodactylum tricornutum (Bacillariophyta) were obtained from the Institute of Hydrobiology, Jinan University, Guangzhou, China, and were routinely cultivated under standardised conditions at constant irradiance (70 μmol m− 2 s− 1) and temperature (23°C) in a 12 h/12 h (light/dark) photoperiod cycle. The artificial seawater was passed

through a 0.45 μm filter prior to being used for culture medium preparation, and an f/2 Obeticholic Acid chemical structure nutrient solution was used in the experiments ( Guillard 1973). The salinity of the artificial seawater was 30 PSU and the initial pH of the culture was approximately 7.0. The microalgal cells were cultivated to the exponential growth phase for use. They were inoculated into 250-mL Erlenmeyer flasks containing fresh f/2 seawater medium; the total experimental volume was 100 mL. The initial cell densities were set at 1.0 × 104 and 1.0 × 105 cells mL− 1 for the two microalgae respectively. Hence, the resulting combinations of initial cell densities of P. donghaiense and P. tricornutum were respectively (1) 1.0 × 104 cells mL− 1 each; (2) 1.0 × 104 and 1.0 × 105 cells mL− 1; (3) 1.0 × 105 and 1.0 × 104 cells mL− 1; and (4) 1.0 × 105 cells mL− 1 Palbociclib manufacturer each. As controls, both microalgae species were cultured individually at initial cell densities of 1.0 × 104 and 1.0 × 105 cells mL− 1. During the maintenance of the experimental

stages, the glass flasks containing algal cells were shaken three times every day by hand at the set time, and they were randomly rearranged to minimise the effects of light or temperature gradients in the plant growth chamber. The growth conditions were the same as stated above, and all experiments were carried out in triplicate. Based on the cell growth characteristics of these microalgae, culture samples were collected in the beginning growth stage (BGS), lag growth stage (LGS), exponential growth stage (EGS) and stationary growth stage (SGS), basically on Day 1, Day 4, Day 7 and Day 10 respectively. Thereafter, an 0.5 mL volume of solution was sampled, and microalgal cell densities were counted using a haemocytometer under an optical microscope after the cells were preserved ( Cai et al. 2013). In order to verify the effects of allelopathic compounds of one microalga on the growth of the other, the culture filtrates of P. donghaiense and P.

5%, and giving a final noninferiority margin of 11%. A sample size of 704 patients, including 352 patients in each treatment group, was considered sufficient for showing noninferiority of TVR twice-daily dosing. Assuming an expected SVR12 rate of 72% in each group and a noninferiority margin of –11%, this sample size provided 90% power to reject the inferiority hypothesis. Secondary efficacy variables included the proportion of patients who achieved RVR, achieved SVR at week 24, experienced a relapse, and experienced on-treatment virological failure. For virological responses, data were analyzed without imputation (“observed” analyses) and using a noncompleter equals failure (NC = F) imputation.

Intermittent missing values were imputed as a “response” if the immediate preceding and following visits showed a response and as “no response” otherwise. If any study drug was prematurely discontinued AZD9291 due to virological failure, “no response” was imputed. If any study drug was prematurely discontinued for another reason (ie, not related to virological failure), missing data were marked as “missing for another reason.” However, missing HCV RNA assessments at the SVR12 visit were not imputed and were considered treatment failures (no SVR). Additional sensitivity analyses were also performed to compare virological response rates (Supplementary

Methods). Descriptive statistics of treatment adherence and the number of patients in each adherence category were reported for TVR Everolimus cell line dosing frequency, timing of intake,

and intake based on the e-diary. This diary captured the amount and timing of TVR dosing relative to the prescribed regimen. Additionally, adherence to dosing of TVR and Sitaxentan PEG-IFN/RBV was measured by dispensed versus returned medications (pill count). Adherence was expressed as the percentage of prescribed doses during the treatment period and categorized by defined thresholds. The e-diary analysis was performed using the ITT population, with missing entries considered 0% adherent. Observed data analyses were also performed. The 95% CIs stated in the report were part of the prespecified statistical analysis and provided an informal comparison within the framework of noninferiority. P values stated in the report for the secondary efficacy variables and subgroup analyses were from post hoc statistical testing. HCV NS3/4A population sequencing was performed on plasma samples at baseline and in the case of virological failure or relapse. The frequency of TVR-resistant variants is presented descriptively. Individual empirical Bayesian estimates of TVR PK parameters were determined using a population PK modeling approach. Blood samples (sparse sampling) were taken at sites with the capabilities for PK sampling at weeks 2, 4, 6, and 8 to determine concentrations of TVR, PEG-IFN, and RBV for adherence assessments as well as for PK evaluations.

The development of the resistance

can be clonal/thus not present at all the tumour sites, supporting a concept of continuing the targeted treatment even beyond tumour progression. Co-targeting molecular pathways such as P13K-AKT and/or RAS-ERK and/or T790M or c-Met along with ErbB receptors may result in more optimal anti-cancer effects. We need to better understand the interplay between various oncogenes and tumour suppressors and thus identify key molecular pathways for Sirolimus chemical structure the treatments. Understanding the reasons for toxicities of targeted therapies will be important for our future rational approaches in combining or sequencing different targeted agents. Co-targeting receptors and their ligand synthesis might help eliminating more effectively receptor activation and downstream oncogenic signalling. New insights of autocrine activation of receptors might lead to new therapeutic approaches. The past successes and failures of therapies led to development of new generation irreversible ErbB family inhibitors and the discovery of new targets, i.e. EML4–ALK fusion gene, ROS, RET and others, which offer significant improvements in clinical outcome for a specific group of patients. The combined regimen strategies of first generation ErbB family inhibitors with anti c-MET inhibitors Pirfenidone nmr are being tested in ongoing clinical trials in hope to further improve therapeutic effect. We have to target

multiple pivotal players of malignant cells on individual basis and in each line of treatment, in order to replace “chemotherapy to fit all” by personalized medicine and thus conquer NSCLC. “
“Takashi Yoshimura received his BS and PhD from Nagoya University. Currently, he is a Professor of Animal Physiology and runs three laboratories:

two laboratories at Nagoya University, in the Graduate School of Bioagricultural Sciences and the Institute of Transformative Bio-Molecules (WPI-ITbM), and another at the National Institute for Basic Biology (NIBB) in Okazaki. In the laboratory at the Graduate selleck chemicals llc School of Bioagricultural Sciences, he studies the underlying mechanisms of vertebrate seasonal reproduction and circadian rhythms using organisms such as tunicates, fish, birds, and mammals. Based on the findings in this laboratory, he is collaborating with cutting-edge synthetic chemists and theoreticians at WPI-ITbM to develop ‘transformative bio-molecules’ that will improve animal production and human health. The NIBB is one of the host institutes for medaka bioresources of the National BioResource Project of Japan, and provides an excellent opportunity to study medaka fish as a model for seasonal biology. Dr Yoshimura is now studying the underlying mechanism of seasonal time measurement using medaka collected from a range of sites across Japan, because medaka from different latitudes exhibit different seasonal responses.

9, 10 and 11 However, the effect of IL-1Ra on bone remodelling after mechanical loading is not well described. In the present study, administration of IL-1Ra diminished OTM by reducing the expression of the pro-inflammatory cytokines NVP-LDE225 clinical trial IL-1β and TNF-α, and by increasing the levels of IL-10, a negative regulator of bone resorption. When an orthodontic

force is applied on teeth, it leads to a transient aseptic inflammation of the periodontium that culminates in bone remodelling.1 In this context, bone resorption is a fundamental step and several cytokines associated to osteoclast differentiation and activation, such as TNF-α and IL-1β, are early released in the periodontium after mechanical loading.3, 4, 18, 19 and 20 Accordingly, the levels of these cytokines were increased in our experimental conditions, whilst the levels of IL-10, a cytokine known to control bone resorption and osteoclast activation,21 were not affected. In view of the importance of this inflammatory milieu to bone resorption, it has been suggested that the control of such inflammation could affect OTM. A previous study showed that an interference with TNF-α activity might decrease

osteoclast migration and, consequently, Rucaparib chemical structure diminish OTM.18 In this regard, administration of IL-1Ra to interfere with IL-1β activity could also alter mechanically induced bone remodelling. IL-1Ra, first called IL-1 inhibitor, was cloned and identified as an IL-1 receptor antagonist after being noticed to bind to IL-1 receptors but not to transduce the same signals that IL-1β did.22 and 23 Thus, IL-1Ra acts by competitively blocking the interactions of IL-1 to their receptors, inhibiting its activities.7 and 8 Indeed, the administration of exogenous

IL-1 receptor antagonist has been shown to be effective in reducing signs of IL-1-related bone resorptive conditions, such as rheumatoid arthritis10 and periodontal disease,11 concomitantly with a reduction of pro-inflammatory cytokines.9 and 11 In this regard, a decreased physiological IL-1Ra expression in gingival crevicular fluid has been shown to correlate with faster OTM in humans.14, 15, 16 and 17 Sirolimus datasheet In the present study, mice treated with IL-1Ra showed significantly diminished OTM and osteoclast numbers than vehicle-treated animals. This phenotype was associated with reduced early release of TNF-α and IL-1β, concomitantly to increased expression of IL-10 on periodontal tissues. The present results give support to previous findings showing that administration of soluble IL-1 receptors reduces the amount of OTM in rats24 and go further when showing that this effect occurs by controlling the expression of cytokines.

, 2007b), and Nova Scotia ( Owens et al., 2011), among others. We wish to emphasize that these declining concentration rates (% day−1) are not ‘decay’ rates of specific molecules

that were all deposited in a single oiling event. The oil that was initially deposited in the marsh in 2010 underwent unequal degrees of decomposition, mixing, evaporation or burial across all sampling sites and had some additional oiling in 2012, and, perhaps, at other times. The decline in concentration is the result of changes in the concentration of a heterogeneous mixture of alkanes and aromatics Dinaciclib whose arrival into the marsh came at various times (e.g., Fig. 5 and Fig. 6), not all at one time; the oil may have arrived with an analyte mixture that was unequally decomposed or diluted as source

materials before marsh deposition, from one oiling event to another, or after deposition. There was a fourfold and sixfold increase in the average concentration BGJ398 chemical structure of target alkanes and PAHs, respectively, immediately after the passage of Hurricane Isaac over Port Sulphur, LA (28 September 2011), located a few km from our study sites. The pre- and post-Isaac data were from plots sampled within 0.5 m of the same plots and are in Fig. 9A and B. These storm conditions, supplemented by normal tidal inundations, would also re-distribute oil into relatively un-oiled wetlands, raising the lowest values, as well. It is interesting that these strong inundation events did not, apparently, dilute the oil concentrations in the wetland sediments. The interpretation of the degree of ‘restoration’ of the oiling of these wetlands depends, in part, on the metric used to define success. The concentration of total target alkanes and PAHs in June 2013 was unless about 1% and 5%, respectively, of the average values measured in February 2011. These numbers might be used

to argue that the wetland was between 99% and 95% restored at that time. The concentration of target alkanes, however, remained 3.6 times higher than the baseline values (May 2010) before the wetland oiling, and are 33 times higher than the baseline concentration of the PAHs. This suggests that impacted wetlands may take decades to recover to the pre-disaster (2010) conditions. We do not, therefore, anticipate a ‘quick’ restoration in these heavily impacted areas and recommend following the long-term persistence of the PAHs within these Louisiana marsh sediments. Most samples had some measurable petroleum hydrocarbons in them, both before the wetlands were oiled in 2010, and afterwards. The very lowest samples from reference sites, representing what we think were the recently un-oiled sites from 2010, averaged 0.98 ± 0.31 mg kg−1 of target alkanes and 23.89 ± 6.07 μg kg−1 of target PAHs, and have been increasing and remaining relatively high. The average of the lowest five concentrations of target alkanes and PAHs rose up to 131X and 829X, respectively, above the pre-oiled conditions (May 2010).

3 μg (i.c.v.) did not significantly change this response (Fig. 2B). No changes in body temperature were seen in animals which received the higher dose of SR140333B or vehicle alone (Fig. 2C). In our attempts to induce a febrile response through the i.c.v. injection of SP we tested different doses ranging from 15 to 1000 ng of SP. The responses, however, were Trichostatin A not consistent since only a few animals showed an increase in body temperature when injected with SP (from 200 ng up to 1000 ng, data not shown). We then treated the animals with captopril 5 μg, i.c.v. 30 min before any injection. The injection of 250 ng of SP did not modify the body temperature of animals; however, the injection of SP

(500 or 750 ng, i.c.v., 2 μl) in captopril-treated animals induced a febrile response which started around 2 h after injection and persisted until the end of the experiment (Fig. 3A). The treatment of the animals with SR140333B, at the same dose that reduced the febrile response to LPS (3 μg, i.c.v.), also completely blocked the febrile response

to SP (500 ng, i.c.v., Fig. 3B). Since no difference was found between the 500 ng SP-treated group and the vehicle plus 500 ng SP-treated group, these data were combined BMS-354825 nmr in Fig. 3C. Intracerebroventricular injection of IL-1β (3.12 ng, i.c.v.) clearly induced a significant febrile response that started around 1 h after injection and persisted until 6 h. Surprisingly, the treatment of the animals with SR140333B (3 μg) did not change this response (Fig. 4A and B). CCL3/MIP-1α (500 pg) also induced a febrile response that started around 3 h and lasted up to 6 h. Similarly, SR140333B was not able to reduce the febrile response induced by this cytokine (Fig. 4C and D). The data reported here show that the febrile response

induced by LPS in rats is dependent on the activation of central, but not peripheral, NK1R. On the other hand, NK1R antagonist treatment (i.p. or i.c.v.) did not affect basal body temperature, suggesting that this peptide is not involved in thermoregulatory mechanisms under normal conditions. Meanwhile, CYTH4 our other findings show that substance P is not involved in the febrile response induced by IL-1β or CCL3/MIP-1α. The NK1R antagonist used here was particularly interesting for the investigation of the peripheral action of SP since there is evidence that this antagonist does not cross the blood–brain barrier (Jung et al., 1994). We found that the intraperitoneal administration of SR140333B at a dose of 1.0 mg/kg was not able to reduce LPS-induced fever. To be sure that this dose was sufficient to reduce SP peripheral effects, we tested the effect of this treatment on plasma extravasation induced by SP. This event is caused by SP directly activating NK1R on endothelial cells (Bowden et al., 1994) or through the release of other mediators (Harrison and Geppetti, 2001 and Maggi, 1997).

With mucosal healing now entrenched as a clinical trial end point and significant evidence demonstrating that mucosal healing modifies the course of the disease, including potentially BIBF 1120 research buy reducing the risk of cancer via primary and secondary prevention, one question that remains is how is this new paradigm

best applied in the clinic? Key issues include how patients in clinical remission should be monitored, and what a clinician should do when active inflammation is encountered on surveillance endoscopy. Assessment of the mucosa and success at achieving healing requires interval evaluation of the bowel, and current evidence further favors histology. This approach implies the need for repeat endoscopic assessment, which has limitations in cost and patient acceptance. Although endoscopy for dysplasia detection Ceritinib is effective and continually improving with technology, the invasiveness, lack of resources, and, probably, cost-ineffectiveness precludes the performance of endoscopy (and biopsies) every 3 to 6 months from the time of diagnosis. Therefore, surrogate markers of mucosal healing, including blood-based and stool-based biomarkers and noninvasive, nonradiation imaging techniques will remain a focus of continued investigation. For example, the use of neutrophil-derived fecal markers, including calprotectin and lactoferrin, has been positively correlated with

endoscopic and histologic activity.43 The key clinical consideration is that baseline determinations of these noninvasive assessments must be obtained and correlated with endoscopic findings to provide Acetophenone meaning to changes over time. In addition, the timing intervals for monitoring remain unclear. Extrapolating from primary clinical trials evaluating mucosal healing, it is known that in the case of anti–TNF-α agents by week 6 to 8, mucosal healing rates (Mayo endoscopic subscore or equivalent

score 0–1) were 42.3% to 62.0% in UC,41, 44, 45 and 46 and by weeks 10 to 12 were 27% to 31% in Crohn’s disease.47 and 48 An important point is that in all of the UC trials, the maintenance rates of mucosal healing were all similar to or lower than that at the induction time point, suggesting that surrogate evaluation as frequently as every 8 weeks could indicate a change in mucosal healing. For now, the most frequent question that arises is related to the performance of routine (guideline-based) surveillance in the asymptomatic patient and the unanticipated inflammation. First, it is important to determine whether the findings are due to an alternative cause such as infection with Clostridium difficile or cytomegalovirus. In the setting of true active inflammation, the clinician should reassess the patient’s symptoms (or lack thereof) and adherence to the existing regimen of therapy, as often patients will self-discontinue or self-reduce a dose without a discussion with their provider; this is especially true when the patient is feeling well.

Nous voilà aujourd’hui devant cette situation ; et sommes-nous armés pour, dans le cadre des incessantes réformes auxquelles nous voici confrontés, pouvoir

accomplir notre mission dans des conditions acceptables ? Jacques Mehl, un des fondateurs, dès 1949 de la Société de médecine de Strasbourg, dont beaucoup d’entre Cabozantinib in vivo nous s’honorent d’avoir été les élèves, a durant toute sa carrière représenté une sorte de pôle humaniste, qui tendait à garder le cap de la médecine du travail vers une éthique simplement hippocratique, pour qui la valeur fondamentale de l’homme, c’est l’homme lui-même. Nous voici loin d’une médecine telle que certains signes laissent penser qu’elle serait souhaitée par les princes, et qui ne viserait qu’à l’immédiat, à la capacité ponctuelle, à la simple notion d’aptitude, à la rentabilité à court terme enfin. On se demande si à notre époque mondiale, nous, dinosaures de la santé au travail comme trop rares jeunes pousses, sommes encore dans les clous de ce qui est souhaitable Jacques Mehl, si je puis

ainsi dire, avait « dressé » ses élèves GSK-3 beta pathway dans un tout autre sens, c’est du moins ce que moi, j’en ai retenu : faire en sorte, tout simplement, d’éviter toute altération de la santé par le fait du travail, comme disait déjà la loi du 11 octobre 1946 et, pour cela, s’en donner les moyens, notamment grâce à la formation initiale et continue qu’il savait si bien dispenser, avec sa rigueur toute alsacienne enrobée d’une souplesse

toute diplomatique. Il était toujours disponible et, même bien longtemps après son départ officiel, il avait su nous rester accessible. Lors des soixante ans de la Société, voici deux MTMR9 ans déjà, il en avait été l’invité d’honneur évident, et nous lui avions fait une mémorable « standing ovation », comme il n’aurait certainement pas dit… Nous avons aujourd’hui perdu un maître et un ami, auquel nous souhaitons rendre l’hommage que nous lui devons A. Pontès “
“Une erreur s’est glissée dans le volume 71, numéro 2/2010 des Archives des maladies professionnelles et de l’environnement. Dans la rubrique Législation, page 218, il fallait lire ce tableau : Arrêté du 28 janvier 2010 modifiant l’arrêté du 22 décembre 2009 portant agrément d’organismes habilités à dispenser la formation à la sécurité des travailleurs intervenant en milieu hyperbare. Listes des organismes agréés pour dispenser la formation à la sécurité des travailleurs intervenant en milieu hyperbare.

Furthermore, the chemical composition of SAS does not

indicate a sensitising potential. The inhalation of respirable particles of SAS produces a time- and dose-related inflammation response of the lung tissue in animal studies. Exposure of rats for 13 weeks to an average concentration of LDK378 mouse 1.3 mg/m3 of pyrogenic SAS resulted in mild reversible pro-inflammatory cell proliferation rather than a pathologically relevant tissue change. Given the low-grade severity of this common lung-tissue response, 1 mg/m3 can be established as NOAEL and LOEL (sub-chronic, 13 weeks). At the LOAEL (5.9 mg/m3) signs of adverse effects were found by the microscopic evaluation of tissues (stimulation of collagen production, increase in lung weight, incipient interstitial fibrosis, and slight focal this website atrophy in the olfactory epithelium). All these effects were reversible following discontinuation of exposure. In the same study also precipitated and surface-treated hydrophobic SAS forms were investigated. All tested forms showed qualitatively

the same effects, however, the pyrogenic form induced somewhat more severe inflammatory effects (for details see Reuzel et al., 1991 and ECETOC, 2006 and OECD, 2004). A dose-dependent inflammatory response after exposure to colloidal silica was found by Lee and Kelly (1992) and Warheit et al., 1991 and Warheit et al., 1995 at concentrations ≥50 mg/m3 (6 h/day, 5 days/week for 2 or 4 weeks). The test material was “Ludox grade CL-X”, obtained from Du Pont Chemicals and consisting of approximately 46% silica in water along with about 0.2% sodium oxide and 5% ethylene glycol. About 200 ppm of formaldehyde was present as a biocide. The pH of the liquid was 9 and the average primary particle size was about 22 nm. MMADs of the particles in

the test atmosphere were reported as 2.9, 3.3 and 3.7 μm for the 10, 50 or 150 mg/m3 groups, respectively. Three months after exposure, all biochemical parameters returned to control values. Lung-deposited silica particles were cleared rapidly from the lungs, with half-times of approximately 40 and 50 days for the 50 and 150 mg/m3 treatment groups, respectively. The lungs did not show formation of fibrotic scar else tissue or alveolar bronchiolarisation. The NOEL for Ludox in this study was at 10 mg/m3. Chen et al. (2008) found that pulmonary inflammation was more severe in old (20 months) rats than in young or adult rats after exposure to amorphous silica particles (purity >99.9%, particle size 37.9 ± 3.3 nm; specific surface area 6.83 × 105 cm2/g, particle number 1.52 × 1010 per μg; purchased from Jiangsu Haitai Nano Material Company Limited, Jiangsu/China). The rats were exposed for a period of 4 weeks at a concentration of 24.1 mg/m3 for 40 min/day. Cardiovascular function changes were observed only in old animals. Takizawa et al. (1988) tested food-grade micronised SAS by oral administration at dose levels of 0, 1.25, 2.5, and 5% for ca.