Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

Knox, J. J.,Barrios, C. H.,Kim, T. M.,Cosgriff, T.,Srimuninnimit, V.,Pittman, K.,Sabbatini, R.,Rha, S. Y.,Flaig, T. W.,Page, R. D.,Beck, J. T.,Cheung, F.,Yadav, S.,Patel, P.,Geoffrois, L.,Niolat, J.,B Oxford University Press 2017 ANNALS OF ONCOLOGY Vol.28 No.6

<P><B>Background</B></P><P>RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points.</P><P><B>Patients and methods</B></P><P>Patients received either first-line everolimus followed by second-line sunitinib at progression (<I>n = </I>238) or first-line sunitinib followed by second-line everolimus (<I>n = </I>233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored.</P><P><B>Results</B></P><P>At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1–26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0–29.8) with sunitinib-everolimus [hazard ratio (HR)<SUB>EVE-SUN/SUN-EVE</SUB>, 1.2; 95% CI 0.9–1.6]. Median OS was 22.4 months (95% CI 18.6–33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8–33.1) for sunitinib-everolimus (HR<SUB>EVE-SUN/SUN-EVE</SUB>, 1.1; 95% CI 0.9–1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences.</P><P><B>Conclusions</B></P><P>Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals.</P><P><B>Clinical Trials number</B></P><P>ClinicalTrials.gov identifier, NCT00903175</P>

The pulsating hot subdwarf Balloon 090100001: results of the 2005 multisite campaign

Baran, A.,Oreiro, R.,Pigulski, A.,Herná,ndez, F. Pé,rez,Ulla, A.,Reed, M. D.,Rodrí,guez-Ló,pez, C.,Moskalik, P.,Kim, S.-L.,Chen, W.-P.,Crowe, R.,Siwak, M.,Armendarez, L.,Binder Blackwell Publishing Ltd 2009 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.392 No.3

<P>ABSTRACT</P><P>We present the results of a multisite photometric campaign on the pulsating B-type hot subdwarf star Balloon 090100001 (Bal09). The star is one of the two known hybrid hot subdwarfs with both long- and short-period oscillations, theoretically attributed to <I>g</I> and <I>p</I> modes. The campaign involved eight telescopes with three obtaining <I>UBVR</I> data, four <I>B</I>-band data and one Strömgren <I>uvby</I> photometry. The campaign covered 48 nights, providing a temporal resolution of 0.36 μHz with a detection threshold of about 0.2 mmag in <I>B</I>-filter data.</P><P>Bal09 has the richest pulsation spectrum of any known pulsating subdwarf B star, and our analysis detected 114 frequencies including 97 independent and 17 combination ones. Most of the 24 <I>g</I>-mode frequencies are between 0.1 and 0.4 mHz. Of the remaining 73, presumably <I>p</I> modes, 72 group into four distinct regions near 2.8, 3.8, 4.7 and 5.5 mHz. The density of frequencies requires that some modes must have degrees ℓ larger than 2. The modes in the 2.8 mHz region have the largest amplitudes. The strongest mode (<I>f</I><SUB>1</SUB>) is most likely radial, while the remaining ones in this region form two nearly symmetric multiplets: a triplet and quintuplet, attributed to rotationally split ℓ= 1 and 2 modes, respectively. We find clear increases of splitting in both multiplets between the 2004 and 2005 observing campaigns, amounting to ∼15 per cent on average. The observed splittings imply that the rotational rate in Bal09 depends on stellar latitude and is the fastest on the equator. We also speculate on the possible reasons for the changes of splitting. The only plausible explanation we find is torsional oscillation. This hypothesis, however, needs to be verified in the future by detailed modelling. In this context, it is very important to monitor the splittings on a longer time-scale as their behaviour may help to explain this interesting phenomenon.</P><P>The amplitudes of almost all terms detected in both 2004 and 2005 were found to vary. This is evident even during one season; for example, amplitudes of modes <I>f</I><SUB>8</SUB> and <I>f</I><SUB>C</SUB> were found to change by a factor of 2–3 within about 50 d during 2005.</P><P>We use a small grid of models to constrain the main mode (<I>f</I><SUB>1</SUB>), which most likely represents the radial fundamental pulsation. The groups of <I>p</I>-mode frequencies appear to lie in the vicinity of the consecutive radial overtones, up to the third one. Despite the large number of <I>g</I>-mode frequencies observed, we failed to identify them, most likely because of the disruption of asymptotic behaviour by mode trapping. The observed frequencies were not, however, fully exploited in terms of seismic analysis which should be done in the future with a larger grid of reliable evolutionary models of hot subdwarfs.</P>

Comparison of Methodologies to Quantify Phytate Phosphorus in Diets Containing Phytase and Excreta from Broilers

de P. Naves, L.,Rodrigues, P.B.,Bertechini, A.G.,Correa, A.D.,de Oliveira, D.H.,de Oliveira, E.C.,Duarte, W.F.,da Cunha, M.R.R. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.7

The use of a suitable methodology to quantify the phytate phosphorus ($P_{phy}$) content in both the feed and the excreta from broilers is required to enable accurate calculation of the catalytic efficiency of the phytase supplemented in the feed. This study was conducted to compare 2 analytical methodologies (colorimetry and also high-performance liquid chromatography with a refractive index detector) in order to calculate the phytase efficiency by utilizing the results from the methodology that was shown to be the most appropriate. One hundred and twenty broilers were distributed in a $(4+1){\times}2$ factorial arrangement, corresponding to 4 diets that were equally deficient in P supplemented with increasing levels of phytase (0, 750, 1,500, and 2,250 units of phytase activity - FTU - per kg of feed) plus 1 positive control diet without phytase, supplied to male and female birds. The result indicated that the colorimetric methodology with an extraction ratio of 1:20 (mass of sample in g:volume of the solvent extractor in mL) was shown to be the most adequate. There was no interaction between the phytase level and the sex of the broilers (p>0.05). Males consumed 12% more $P_{phy}$ than did females (p<0.01), but the sex of the broilers did not affect (p>0.05) the excretion and retention coefficient of $P_{phy}$. The increase in the phytase level of the diet reduced (linear, p<0.01) the $P_{phy}$ excretion. The greatest $P_{phy}$ retention was estimated at 87.85% when the diet contained 1,950 FTU/kg (p<0.01), indicating that it is possible to reduce the inorganic P in the formulation at an amount equivalent to 87.85% of the $P_{phy}$ content present in the feed, which, in this research, corresponds to a decrease in 2.86 g of P/kg of the feed.

Toward high efficiency organic photovoltaic devices with enhanced thermal stability utilizing P3HT-b-P3PHT block copolymer additives

Zhu, M.,Kim, H.,Jang, Y.,Park, S.,Ryu, D.,Kim, K.,Tang, P.,Qiu, F.,Kim, D.,Peng, J. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.47

<P>Organic photovoltaics (OPVs) have drawn an extensive amount of attention due to their low cost, processibility and flexibility. However, a cell based on a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) has a limited power conversion efficiency (PCE) due to the short exciton diffusion length of similar to 10 nm. We address this issue by designing a series of all-conjugated diblock copolymers, poly(3-hexylthiophene)-b-poly(3-(6-diethylphosphonatohexyl) thiophene) (P3HT-b-P3PHT), intended for use as additives to improve the performance of P3HT:PC61BM-based photovoltaic devices. The PCE of the devices improved from 3.30% to 4.03% with the addition of P3HT-b-P3PHT (3 : 1). The thermal stability of devices with P3HT-b-P3PHT additives improved significantly relative to that of the P3HT:PC61BM reference device, where the devices including a copolymer with a higher P3PHT content exhibited a better thermal stability. It was found that the fill factor (FF) could be regulated by simply varying the block ratio of P3HT-b-P3PHT and played a crucial role in improving both the PCE and the thermal stability. The P3HT-b-P3PHT diffused at the P3HT:PC61BM interface, improved the miscibility between P3HT and PC61BM, optimized the nanoscale morphology of the photoactive layer, and reduced the active layer roughness, all of which improved the FF and thus contributed to an improvement in device performance.</P>

p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts of Oral Squamous Cell Carcinomas and Development of Local Recurrence

Sawair, F,Hassona, Y,Irwin, C,Stephenson, M,Hamilton, P,Maxwell, P,Gordon, D,Leonard, A,Napier, S Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. Materials and Methods: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. Results: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

Effect of Methionine Source and Dietary Crude Protein Level on Growth Performance, Carcass Traits and Nutrient Retention in Chinese Color-feathered Chicks

Xi, P.B.,Yi, G.F.,Lin, Y.C.,Zheng, C.T.,Jiang, Z.Y.,Vazquez-Anon, M.,Song, G.L.,Knight, C.D. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.6

A total of 1,200 LinNan Chinese color-feathered chicks were used to study the effects of methionine source [DL-2-hydroxy-4-methylthio-butanoic acid (HMTBa) or DL-methionine (DLM)] and dietary crude protein (CP) level on growth performance, carcass traits, and whole-body nitrogen and fat retention. The trial was designed as a $2{\times}2$ factorial arrangement, including two CP levels (adequate and low) and two methionine sources (HMTBa and DL-methionine). Diets were formulated for three phases, starter (0-21 d), grower (21-42 d), and finisher (42-63 d). Chicks fed HMTBa had higher daily gain and improved feed efficiency than DLM during the grower phase (p<0.05). A significant two-way interaction was observed for growth performance during the finisher phase and overall (0-63 d). Growth performance was greater for chicks fed HMTBa than DLM on adequate-CP diets (p<0.05), but this was not observed at low-CP level (p>0.05). Chicks fed low-CP diets grew slower, used feed less efficiently during the grower, finisher phase and overall. On d 42, regardless of dietary CP levels, birds fed HMTBa had higher carcass weights, breast and thigh weights than DLM-fed birds (p<0.04). Birds fed low-CP diet had lighter carcass weights and less breast muscle, thigh muscle, and dressing percentage at the end of starter, grower and finisher phases (p<0.05). Whole body composition analyses found that birds fed HMTBa tended to contain more protein and less fat compared to those chicks fed DLM at the end of the starter phase (p<0.10). Low-CP diets increased CP concentration in the whole body at the end of the finisher phase (p = 0.05). HMTBa supplementation increased whole-body N retention rate during the finisher phase and overall (p<0.01), and low-CP diets reduced N intake and whole-body fat retention during the finisher phase and overall (p<0.05). In summary, HMTBa was better than DLM on an equimolar basis for growth performance, carcass traits, and N retention in Chinese color-feathered chicks. Low-CP diets lowered growth performance as well as carcass traits in color-feathered birds, probably due to imbalanced AA profiles.

Report of the CCQM-K97: measurement of arsenobetaine standard solution and arsenobetaine content in fish tissue (tunafish)

Ma, L D,Wang, J,WEI, C,Kuroiwa, T,Narukawa, T,Ito, N,HIOKI, A,CHIBA, K,Yim, Y H,Lee, K S,Lim, Y R,Turk, G C,Davis, C W,Mester, Z,Yang, L,McCooeye, M,Maxwell, P,Cankur, O,Tokman, N,Coskun, F G BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.-

<P></P> <P>The CCQM-K97 key comparison was organized by the inorganic analysis working group (IAWG) of CCQM as a follow-up to completed pilot study CCQM-P96 and P96.1 to test the abilities of the national metrology institutes to accurately quantitate the mass fraction of arsenobetaine (AsB) in standard solution and in fish tissue. A pilot study CCQM-P133 was parallelized with this key comparison. National Institute of Metrology (NIM), China and National Metrology Institute of Japan (NMIJ) acted as the coordinating laboratories.</P> <P>Six NMIs participated in CCQM-K97 and two institutes participated in CCQM-P133, and all of them submitted the results. Some NMIs submitted more than one results by different methods. The results were in excellent agreement with each other, and obviously better than those of previous P96 and P96.1. Therefore the calibrant which each NMI used was comparable. It shows that the capabilities of some of the participants have been improved after the previous pilot studies.</P> <H2>Main text</H2> <P> To reach the main text of this paper, click on <A HREF='http://www.bipm.org/utils/common/pdf/final_reports/QM/K97/CCQM-K97.pdf'>Final Report</A>. Note that this text is that which appears in Appendix B of the BIPM key comparison database <A HREF='http://kcdb.bipm.org/'>kcdb.bipm.org/</A>.</P> <P>The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).</P>

Effect of Microbial Phytase on Performance, Nutrient Absorption and Excretion in Weaned Pigs and Apparent Ileal Nutrient Digestibility in Growing Pigs

Zeng, Z.K.,Piao, X.S.,Wang, D.,Li, P.F.,Xue, L.F.,Salmon, Lorraine,Zhang, H.Y.,Han, X.,Liu, L. Asian Australasian Association of Animal Productio 2011 Animal Bioscience Vol.24 No.8

Two experiments were conducted to evaluate the efficacy of Trichoderma reesei derived phytase for pigs fed diets with fixed calcium to total phosphorus ratios (1.5:1). In Exp. 1, 280 weaned pigs (initial BW of $10.32{\pm}1.94$ kg) were allocated to one of five dietary treatments on the basis of weight and gender in a randomized complete block design. Treatments were the low phosphorus (0.6% Ca, 0.4% total P and 0.23% available P) diets supplemented with 0, 250, 1,000, or 2,000 FTU phytase/kg of diet and a positive control diet (PC; 0.85% Ca, 0.58% total P and 0.37% available P). The treatments were applied to seven pens with eight pigs per pen, half male and half female. In Exp. 2, six barrows fitted with ileal T-cannula (initial BW = $35.1{\pm}1.6$ kg) were assigned to three dietary treatments with a double $3{\times}3$ Latin square design. The dietary treatments were the low-phosphorus diet (0.53% Ca, 0.34% total P and 0.14% available P), the low phosphorus diet plus 1,000 FTU phytase/kg and a positive control diet (0.77% Ca, 0.50% total P and 0.30% available P). In Exp. 1, there were linear increases (p<0.01) in weight gain, phosphorus absorption, bone strength, calcium and phosphorus content of fat-free dried bone and plasma phosphorus concentrations with increasing dose rate of phytase. The performance of pigs fed the diets with 250, 1,000, or 2,000 FTU of phytase/kg did not differ from pigs fed the PC diet. Pigs fed diets with 1,000 or 2,000 FTU of phytase/kg did not differ from pigs fed the PC diet in bone characteristics. The apparent digestibility of dry matter, crude protein, ash and energy was not affected by dietary treatment. However, pigs fed the PC diet excreted more fecal phosphorus (g/d, p<0.01) and fecal phosphorus per BW gain (g/kg) than pigs fed the diets with phytase. Phytase linearly decreased (p<0.01) fecal phosphorus excreted per BW gain (g/kg), plasma calcium concentration as well as plasma and bone alkaline phosphatase activity. In Exp. 2, phytase supplementation in the low-P diet increased (p<0.05) the apparent ileal digestibility (AID) of Ca, P, leucine, lysine, phenylalanine, alanine and cysteine, tended to AID of crude protein, isoleucine, threonine, asparagine and serine. In conclusion, the novel phytase originated from Trichoderma reesei is effective in releasing Ca, P, and amino acids from corn soy based diet for pigs.

Effects of Adding Super Dose Phytase to the Phosphorus-deficient Diets of Young Pigs on Growth Performance, Bone Quality, Minerals and Amino Acids Digestibilities

Zeng, Z.K.,Wang, D.,Piao, X.S.,Li, P.F.,Zhang, H.Y.,Shi, C.X.,Yu, S.K. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.2

Two experiments were conducted to evaluate the efficacy of feeding an Escherichia coli (E. coli) derived phytase to pigs fed P deficient, corn-soybean meal diets. In Exp. 1, one hundred and twenty crossbred piglets ($9.53{\pm}0.84$ kg) were allocated to one of five treatments which consisted of four low P diets (0.61% Ca, 0.46% total P and 0.24% non-phytate P) supplemented with 0, 500, 1,000, or 20,000 FTU/kg E. coli phytase as well as a positive control formulated to be adequate in all nutrients (0.77% Ca, 0.62% total P and 0.42% non-phytate P). The treatments were applied to six pens with four pigs per pen for 28 days. In Exp. 2, ten crossbred pigs ($19.66{\pm}1.16$ kg) fitted with ileal T-cannula were used in a nutrient balance study. The pigs were assigned to treatments similar to those used in Exp. 1 in a doubly replicated $5{\pm}4$ incomplete Latin square design (5 diets with 4 periods). Each period consisted of a 5-d adjustment period followed by a 3-d total collection of feces and urine and then a 2-d collection of ileal digesta. Supplementation with phytase linearly increased (p<0.05) weight gain, feed intake, feed efficiency, bone breaking strength and fat-free dry and ash bone weight. There were linear increases (p<0.01) in the apparent ileal digestibility (AID) of DM, GE, CP, Ca, total P, inositol hexaphosphate ($IP_6$) and some AA with increasing dose of E. coli phytase. Pigs fed 20,000 FTU/kg had a greater (p<0.05) AID of IP6 (80% vs 59% or 64%, respectively) than pigs fed diets with 500 or 1,000 FTU/kg phytase. There were linear increases (p<0.05) in the total tract digestibility of Ca, total P, Na, K, Mg, and Zn as well as in the retention of Mg and Zn with increased phytase dose. The retention and utilization of Cu, and the total tract digestibility of CP and Cu quadratic increased (p<0.05) with increased phytase dose. In conclusion, supplementation of 500 FTU of phytase/kg and above effectively hydrolyzed phytate in low-P corn-soybean diets for pigs. In addition, a super dose of phytase (20,000 FTU/kg) hydrolyzed most of the IP6 and consequently further improved mineral use, protein utilization and performance.

Strength enhancement of high entropy alloy HfNbTaTiZr by severe plastic deformation

Č,í,ž,ek, J.,Hauš,ild, P.,Cieslar, M.,Melikhova, O.,Vlasá,k, T.,Janed,ek, M.,Krá,l, R.,Harcuba, P.,Luká,d,, F.,Zý,ka, J.,Má,lek, J.,Moon, J Elsevier 2018 Journal of alloys and compounds Vol.768 No.-

<P><B>Abstract</B></P> <P>Refractory metal high entropy alloy HfNbTaTiZr with ultrafine grained structure and grain size of ≈80 nm was processed by high pressure torsion. The development of microstructure, lattice defects and mechanical properties with increasing strain was examined. Grain refinement of HfNbTaTiZr alloy deformed up to the equivalent strain <I>e</I> ≈ 50 resulted in a significant enhancement of strength while keeping sufficient ductility. However, further straining <I>e</I> > 100 led to a decrease of strength and the loss of ductility due to the decomposition of solid solution facilitated by vacancies introduced by severe plastic deformation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> High entropy alloy HfNbTaTiZr was nanostructured by high pressure torsion. </LI> <LI> Grain size of 80 nm was achieved by deformation to the equivalent strain e = 5. </LI> <LI> Structure refinement resulted in remarkable enhancement of strength of the alloy. </LI> <LI> Ductility remains sufficient for good workability. </LI> <LI> Further deformation to very high strains resulted in loss of strength. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>