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The utility of the International Working Group (IWG) 2006 response criteria for myelodysplastic syndromes (MDS) as a surrogate endpoint for outcomes is unclear. We assessed the validity of the IWG 2006 response criteria in a large cohort of higher‐risk MDS patients (pts) treated at centers from the MDS Clinical Research Consortium. The best overall response rate (ORR) by IWG 2006 criteria to first‐line therapy among 597 evaluable pts was 38% and include complete response (CR) 16%, marrow CR (mCR) 2%, partial response (PR) 10%, hematological improvement (HI) 10%, stable disease (SD) 33%, and progressive disease (PD) 24%. CR was associated with a better overall survival (OS) compared to all other response groups (P, In higher risk MDS patients responses associated with restoration of effective hematopoiesis namely complete remission (CR) are associated with better outcomes.Marrow CR without hematological improvement outside context of allogeneic hematopoietic stem cell transplant should not be included in response criteria assessing new therapeutic agents in MDS.

Some patients classified as having lower-risk (LR)-disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR-Prognostic System (LR-PSS), and the revised IPSS (IPSS-R) in a large cohort of patients classified as having IPSS LR-MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR-MDS (i.e. low and intermediate-1) using Kaplan-Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44-52). Median follow-up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR-PSS (0.74, 95% CI, 0.70-0.78) than IPSS-R (0.64, 95% CI, 0.60-0.67) and IPSS (0.64, 95% CI, 0.60-0.68). Similarly, AIC values indicating the goodness of the fit were better for LR-PSS than IPSS-R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR-PSS assigned 25.1% and 37.4% of patients with IPSS LR-MDS into LR-PSS Category 3 and IPSS-R Categories ≥Intermediate, respectively. Of 291 patients (25.5%) who survived ≤24 months from diagnosis, only 37.1% and 45% were classified as LR-PSS category 3 and IPSS-R categories ≥Intermediate, respectively (P = 0.06). While both LR-PSS and IPSS-R distinguish groups with varied survival outcome among patients with IPSS LR-MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease-modifying therapies.

The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale. (C) 2014 Wiley Periodicals, Inc.

Summary Introduction: Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated. Materials and methods: Platelet reactivity was assessed by the light transmission aggregometry and TxB2 assay in 423 patients with coronary artery disease (CAD) on aspirin. High residual platelet reactivity (RPR) was defined by ≥20% and ≥70% maximal aggregation stimulated with 0.5 mg/mL arachidonic acid (AA) and 10 μm ADP, respectively. Moderate RPR was considered aggregation ≥20% with AA, ≥70% with ADP, or ≥1 ng/mL stimulated TxB2. Fourteen P2RY1 and 35 P2RY12 single nucleotide polymorphisms (SNPs) were genotyped. Results: High RPR was detected in 24% of the patients. Moderate RPR was observed in 31% with AA, 57% with 5 μm ADP, and 82% with 10 μm ADP. Stimulated TxB2 was ≥1 ng/mL in 23% of patients. P2RY12 SNP rs9859538 was associated with high RPR (OR = 2.16, 95% CI = 1.24–3.75, P-value = 0.004). Four P2RY12 SNPs, rs1491974, rs10513398, rs3732765, and rs10935841, showed association with moderate RPR (OR = 1.79–2.94, P-value = 0.04–0.028), while five, rs7615865, rs1388623, rs1388622, rs7634096, and rs7637803, were associated with low RPR (OR = 0.50–0.55, P-value = 0.008–0.026), following ADP stimulation. TxB2 level

Effects of smoking time and temperature on optimal chipotle pepper production were evaluated and optimized using the response surface methodology. Batches of red jalapeno peppers were smoked under different temperatures (65.8, 70, 80, 90, 94.1C) and times (0.96, 2, 4.5, 7, 8 h). Afterward, samples were evaluated for moisture, rheological properties and total phenols. Samples were then dried from 80C to between 0.123 and 0.204 kg H2O/kg dry matter and evaluated for rheological properties, texture, rehydration, color and phenols. Phenol content, rehydration ratio, firmness of peppers, and rheological properties and color of puree were affected (P < 0.05) by both temperature and time. Best smoking conditions used temperatures of 74–79C, and times between 8.0 and 7.4 h resulting in viscosities of 5.1– 6.5 Pa·s with phenol content of 110–120 mg/kg, rehydration ratios of 3.7–4.1, firmness of 1.27–1.49 N and acceptable color. Smoking time was significantly reduced and quality maintained.

The present investigation evaluated the chemical and thermal properties using lime and alternative calcium salts, and their effect on the characteristics of masa and tortilla obtained in a two-step nixtamalization process. White dent corn was cooked in calcium hydroxide solution (1.2% [w/v]; 1:3 maize : water ratio) at 80C (30 min), and the calcium hydroxide was replaced either by calcium chloride or lactate at calcium equilibrated concentration (30 min), and steeped in a cooking solution for 2,400 min. Grains were analyzed for water and calcium absorption, and apparent diffusion coefficients were calculated. Thermal properties of flour made from these grains were also determined. Additionally, the masa and tortilla made with nixtamalized corn flours were analyzed for texture and color, and an acceptability test was performed on the tortilla. Water absorption showed a notable increase during cooking, approaching an asymptotic maximum absorption after 8 h of steeping for all treatments. The maximum calcium absorption was obtained in stepwise nixtamalization with solutes of CaCl2 and C6H10O6Ca. The water apparent diffusion coefficients were adequately described by Fick's model and it was found that C6H10O6Ca showed the highest value (5.5901 × 10−10 m2/s), while that for calcium diffusion the model gave low fits. The thermal analysis showed that gelatinization temperatures were affected significantly (P

Polarized gastrointestinal epithelial cells form tight junctions that spatially separate apical and basolateral cell membrane domains. These domains harbor functionally distinct proteins that contribute to cellular homeostasis and morphogenesis. Transforming growth factor beta (TGFbeta) is a critical regulator of gastrointestinal epithelial cell growth and differentiation. Functional assays of vectorial TGFbeta signaling and immunofluorescence techniques were used to determine the localization of TGFbeta receptors and ligand secretion in polarizing Caco-2 cells, a colon cancer cell line. Results were compared to the nontransformed MDCK cell line. In both Caco-2 and MDCK cells, addition of TGFbeta1 to the basolateral medium resulted in phosphorylation of Smad2. No phosphorylation was observed when TGFbeta1 was added to the apical chamber, indicating that receptor signaling is localized at the basolateral membrane. In support of this, immunofluorescence and biotinylation assays show receptor localization along the basolateral membrane. Secretion of TGFbeta1 from MDCK and Caco-2 cells into the apical or basolateral medium was measured by ELISA. Interestingly, secretion was exclusively apical in the nontransformed MDCK line and basolateral in transformed Caco-2 cells. Collectively, these results show basolateral domain specificity in localization of the TGFbeta receptor signaling apparatus. These observations have important implications for understanding the biology of TGFbeta in polarized epithelia, including elements of communication between epithelial and mesenchymal layers, and will prove useful in the design of therapeutics that target TGFbeta function.

Summary The effects of low temperature blanching in calcium chloride solution of jalapeno peppers prior to freezing, on firmness retention, pH, methanol, colour and calcium ions of the product, were evaluated by response surface methodology. Texture, methanol content and pH were affected by all of the variables studied (P = 0.05). The optimum response was obtained at temperatures of 63.3–66 °C, calcium chloride concentrations of 0.17–0.21 m, immersion time of 11.6–14.4 min, with a holding time after blanching of 56.6–66.1 min. Microscopic evaluation of the thawed pepper showed that blanching in CaCl2 solution provided a protective effect in maintaining cell wall integrity.

The effect of low-temperature blanching and drying processes on the ultrastructural and physical properties of Anaheim chilli pepper was studied and optimum conditions to provide a final product with maximum firmness were determined. Lots of Anaheim pepper were blanched in water for 4min at 48, 55, 65, 75 and 82 ◦ C and maintained for hold times of 35, 45, 60, 75 and 85min, blanched again for 4min at 96 ◦ C and dehydrated at 53, 60, 70, 80 and 87 ◦ C. After treatment the samples were rehydrated in water at 30 ◦ C. Rehydration ratio, texture and structural changes were evaluated. Optimisation used a second-order rotatable central composite design. Texture and rehydration ratio were affected by blanching temperature and the interaction of blanching temperature with hold time (p ≤ 0.05); drying temperature did not show a significant effect. The best results, ie those which gave greatest firmness, were obtained by blanching at 64 ◦ C for 4min, holding for 55min after blanching, followed by a second blanching at 96 ◦ C for 4min and then drying at 70 ◦ C. Evaluation of the rehydrated dried pepper by microscopy showed that low-temperature blanching close to the optimum conditions provided a protective effect in maintaining cell wall integrity. The results of processing increased firmness in the rehydrated product by a factor of 1.97.  2003 Society of Chemical Industry

Diced green bell pepper was blanched twice, once at 51-79 °C for 19-61 min, and once at 95 °C for 3 min, and dried. The firmness of rehydrated samples was measured by puncture, and optimum conditions assessed by response surface methodology. The optimized model showed that, blanching at 65 °C for 49 min gave a 64% increase in puncture force over the control. The optimum temperature was used to evaluate the effect of adding CaCl 2 . The dices were blanched twice, once at 65 °C for 3 min in either 0 or 4% CaCl 2 , secondly in either 0 or 2% CaCl 2 solution at 95 °C for 3 min. In the second case the dices had been held at room temperature for 0-30 min before treatment. Adding CaCl 2 increased puncture force significantly (P ≤ 0.05). The best results, those which gave greatest firmness, were obtained by blanching at 65 °C for 3 min in 4% CaCl 2 , holding for 16 min after blanching, followed by a secondary blanching at 95 °C in 2% CaCl 2 . Du poivron vert en cube a ete blanchi deux fois puis seche. La fermete du poivron rehydrate a ete mesure et les conditions optimales ont ete determinees: le blanchiment a 65° pendant 49 min donne les meilleurs resultats. Le poivron en cube a ensuite ete blanchi a 65° pendant 3 min.puis 95° pendant 3 min. en presence de chlorure de calcium a concentration variable, a chaque fois. Les meilleurs resultats sont obtenus pour CaCl 2 a 4% puis CaCl 2 a 2% pour le deuxieme blanchiment.

The effects of low-temperature long-time blanching of diced jalapeno pepper prior to freezing on extrusion force, color and pH of the product were evaluated and optimized by response surface methodology. The blanch temperature was the most important factor, while hold time had no significant effect on product quality. Maximum extrusion force and color parameter a*(green-red) correlated with temperature. The pH and the color parameters L*(brightness) and b*(blue-yellow) showed no significant variation with the experimental variables. The recommended blanch temperature of 55C produced a firmness value of 779N and a color value of 10.55 of parameter a* in frozen jalapeno peppers.

The cowpea [Vigna unguiculata (L.) Walp] is an important crop in many countries of tropical Africa, Asia and South America. Compared with other leguminous crops, little is known about the population structure of the cowpea and the partitioning of genetic diversity between cultivated and wild cowpea. One hundred and twelve accessions of cultivated cowpea (V. unguiculata ssp. unguiculata) and 43 of wild cowpea (V. unguiculata ssp. dekindtiana) were evaluated for genetic diversity at 26 isozyme loci. Cultivated accessions were characterized by very low genetic diversity (Ht = 0.029), with only six polymorphic loci. Four of these polymorphic loci displayed one very common allele and one rare allele. Accessions possessing these rare alleles were dispersed throughout Africa and a geographical center of isozyme diversity was not evident. Cultivated groups biflora (the catjang) and sesquipedalis (the yard-long bean) could not be differentiated from the cowpea. Wild cowpea, on the other hand, were highly diverse (Ht = 0.168), with 19 out of 26 loci polymorphic. Our data indicate introgression from wild to cultivated must be very rare. Six wild accessions displayed high identity with the cultivated cowpea. Wild cowpea may, therefore, be the progenitor of the cultivated cowpea. Because these wild accessions were dispersed throughout equatorial Africa, there is no isozyme evidence for a narrowly defined center of domestication. Financial assistance was provided by the International Board for Plant Genetic Resources (IBPGR).

Whole green bananas were blanched in water at 50, 60, 70, 80, 90, and 100°C for 2, 15, and 30 min using a factorial design then peeled, sliced and fried in oil to make chips. Crispness was measured using a bending-snapping test in the TA.XT2 Texture Analyzer. Significant interactions were found between blanch time and temperature and crispness of chips. A second experiment was then performed using a central composite design and blanch temperatures from 41.7 to 98.3°C. Response surface analysis predicted that crispiest chips should be produced at blanching conditions of 69°C and 22 min.

A modified drop-shatter test apparatus was used to study the primary breakage of particles of two solid fuels. In this apparatus many particles could be subjected to just one impact under known conditions. About 100000 particles of each fuel, sorted by size and shape into eight separate groups, were dropped from four different heights and the fragments thus formed were sifted to determine their size distributions, that is the experimental breakage functions. The interior of particles, of regular or irregular shape, fails under tension and the resulting fragmentation is due to stress-activated volume flaws which give rise to coarse fragments whose distribution can be represented by a theoretical breakage function of the form where z is the relative size of the fragments and γ is the number of stress-activated volume flaws per particle. The average values of γ, given by μγ = λ/(1 – e−λ), ranged from about one to five, corresponding to the formation of two to six coarse fragments per broken particle. The probability of breakage was log-normally related to μγ.

Carbonated apple juice, produced at various levels of soluble solids (Brix) and carbonation, was studied using response surface methodology with treatment levels based on a rotatable design. Sensory attributes of aroma, sweeteners, sourness, body, carbonation level, and acceptability were evaluated and response models derived where appropriate. Aroma intensity was not significantly affected by level of soluble solids or carbonation level. A model including linear and quadratic effects was derived for sweetness response and perceived carbonation level. Sourness and body (mouthfeel) were modeled with significant linear effects. The model derived for the acceptability of the juice had a ridge of high acceptability running through the range of typical soluble solids and carbonation levels.