Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer.

BACKGROUND: Cediranib is a potent oral vascular endothelial growth factor (VEGF) signalling inhibitor with activity against all three VEGF receptors. The International Collaboration for Ovarian Neoplasia 6 (ICON6) trial was initiated based on evidence of single-agent activity in ovarian cancer with acceptable toxicity. METHODS: The ICON6 trial is a 3-arm, 3-stage, double-blind, placebo-controlled randomised trial in first relapse of platinum-sensitive ovarian cancer. Patients are randomised (2 : 3 : 3) to receive six cycles of carboplatin (AUC5/6) plus paclitaxel (175 mg m(-2)) with either placebo (reference), cediranib 20 mg per day, followed by placebo (concurrent), or cediranib 20 mg per day, followed by cediranib (concurrent plus maintenance). Cediranib or placebo was continued for 18 months or until disease progression. The primary outcome measure for stage I was safety, and the blinded results are presented here. RESULTS: Sixty patients were included in the stage I analysis. A total of 53 patients had received three cycles of chemotherapy and 42 patients had completed six cycles. In all, 19 out of 60 patients discontinued cediranib or placebo during chemotherapy because of adverse events/intercurrent illness (n=9); disease progression (n=1); death (n=3); patient decision (n=1); administrative reasons (n=1); and multiple reasons (n=4). Grade 3 and 4 toxicity was experienced by 30 (50%) and 3 (5%) patients, respectively. No gastrointestinal perforations were observed. CONCLUSION: The addition of cediranib to platinum-based chemotherapy is sufficiently well tolerated to expand the ICON6 trial and progress to stage II.

Lean color characteristics of bullock and steer beef.

Twelve young bulls and 12 steers were slaughtered and the carcasses were fabricated at 48 h postmortem. Top rounds, bottom rounds, and rib eyes were vacuum-packaged and stored at 0 degrees C until 21 d postmortem. After subprimal storage, steaks were removed from each cut and displayed under simulated retail conditions for 3 d. Consumer panelists (n = 110) showed little difference in buying preference for top round, bottom round, and rib eye steaks from steers vs bullocks. Also, consumer panelists could not detect color differences between steaks from steers and bullocks. Experienced panelists (n = 6) detected brighter (P less than .05) muscle color for top round and rib eye steaks from steers but detected no difference in muscle color of bottom round steaks from bullocks and steers. Generally, overall desirability scores favored steaks from steer carcasses. This was particularly true of rib eye steaks. Sex-class of carcass did not affect aerobic plate counts of top round, bottom round, or rib eye steaks either before or after 3 d of retail display. Muscle pH was lower for top round and rib eye steaks from steer carcasses; however, the magnitude of this difference was not large enough to affect retail display stability. Muscle pH of bottom round steaks was not affected by sex-class. Although experienced panelists could detect differences in visual appearance of beef retail cuts from steers and bullocks, consumer panelists did not show a clear purchase preference for steer vs bullock beef. These data suggest that beef retail cuts from bullocks are acceptable in visual appearance.

Storage and display characteristics of electrically stimulated, hot-boned and nonstimulated, cold-boned beef.

One side, randomly selected from each of 33 carcasses from forage-fed steers, was electrically stimulated within 30 min of exsanguination and hot-bonded (ESHB). Opposite sides were not electrically stimulated and were cold-boned (NESCB) following a 24 h chill (0°C). From 17 ESHB sides, portions of the longissimus dorsi (LD) and semimembranosus (SM) muscles were removed and immediately vacuum packaged. LD and SM muscles were removed from the remaining 16 ESHB sides, wrapped in polyvinyl chloride film, chilled (0°C) for 22 h and then vacuum packaged. LD and SM muscles from NESCB sides (n = 33) were removed and the vacuum packed at 24 h post mortem. Whole muscle characteristics were evaluated initially and after storage periods of 7, 14 or 21 days and steaks were displayesd for 5 years thereafter. Neither hot versus cold-boning nor storage for 21 days affected retail display characteristics of LD and SM steaks (P > 0·05). As retail display time increased, retail lean color, fat color and overall appearance scores decreased.

Hand-rearing baboons for laboratory investigations.

To conduct laboratory studies in unsedated animals that were similar anatomically and physiologically to man, five full term baboons (four Papio cynocephalus anubis, one Papio cynocephalus cynocephalus) were hand-reared. These infants were used as unsedated animal models in short-term lung clearance studies conducted from birth to 2 years of age. The hand-rearing techniques described here encouraged the formation of an infant-human rearer bond that permitted us to control the level of expressed aggressive behavior as the infant matured. These techniques resulted in baboons which displayed subordinate behavior, showed positive reception to human contact (without evidence of negative stereotypic behavioral anomalies) and remained cooperative subjects for our investigations of short-term pulmonary clearance. The baboons generally were above average in weight in comparison to conspecifically-reared baboons of similar age, sex and species. Representative lung retention curves presented on one baboon demonstrate the feasibility of lung clearance studies in these hand-reared animals. Due to its suitability for unsedated studies, this baboon model may be considered for other types of laboratory investigations.

Palatability characteristics of loin steaks from Charolais crossbred bulls and steers.

Loins from 1 2 - blood or 3 4 - to 7 8 - blood Charolais bulls (n = 60) and steers (n = 64) were obtained at 24 h post mortem from electrically stimulated sides and, at 12 days post mortem, steaks were removed and frozen. Shear force values were higher (P < 0·001) and sensory panel evaluations of tenderness and overall palatability were lower (P < 0·001) for steaks from bulls than from steers. No differences (P > 0·05) in connective tissue amount or off-flavour were detected for steaks from bulls versus steers. Significant correlations between carcass secondary sex characteristics and sensory panel evaluations of tenderness were noted, but the coefficients were not of a magnitude to be considered predictive of tenderness.

Cutability comparisons of Charolais crossbred bulls and steers.

Seventy-two sides (eighteen sides from each sex-breed group) from carcasses of half-blood or three-quarters-to-seven-eighths-blood Charolais bulls or steers of known history and age, handled alike from weaning to slaughter, were used. All cattle were fed in a commercial feedlot (average days-on-feed was 186) and slaughtered in a commercial packing plant. Comparisons were made for percentages of (1) untrimmed wholesale cuts, (2) partially boneless subprimals (trimmed of fat in excess of 1·9 cm), (3) partially boneless retail-ready cuts (trimmed of fat in excess of 0·95 cm) and (4) boneless retail-ready cuts (trimmed of fat in excess of 0·95 cm). Bulls had higher percentages than steers of chuck and round at all stages of trim. Steers had higher percentages of untrimmed, wholesale loin and partially boneless shortloin (1·9 cm fat) than bulls but steer percentages of shortloin cuts trimmed to 0·95 cm of fat did not differ from those of bulls. Bulls averaged 48·05%, while steers averaged 45·45%, major boneless, closely trimmed retail-ready cuts. After the lean trim was adjusted to 25% chemical fat, bulls had 27·70% lean trim and 5·65% fat trim while steers had 24·30% lean trim and 12·15% fat trim. No difference in the percentage of retail-ready cuts was attributable to breed; however, the three-quarters-to-seven-eighths-blood Charolais group had a lower percentage of standardized fat trim and a slightly higher percentage of bone than the half-blood group.

Characterization of cutability and palatability attributes among different slaughter groups of beef cattle.

Fifteen slaughter cattle from five groups (Charolais crossbred bulls, Brahman crossbred steers, Holstein steers, mixed-Exotic crossbred heifers and Hereford-Angus crossbred steers) were randomly selected from a commercial feedlot. Time-on-feed was 108, 114, 102, 108 and 145 days for the aforementioned groups, respectively. Carcasses from Charolais crossbred bulls had the highest percentage yield of chuck and round, but the lowest percentage yield of loin; hereford-Angus crossbred steers had the lowest percentage yield of round and Holstein steers had the lowest percentage yield of rib. Carcasses from Charolais crossbred bulls had the highest percentage yield of major retail-ready subprimals and lean trim, Hereford-Angus crossbred steers had the highest percentage yield of fat trim and Holstein steers had the highest percentage yield of bone from the major wholesale cuts. Mean percentage yields of closely trimmed, boneless retail cuts were highest for carcasses from the bulls and lowest for carcasses from the Hereford-Angus steers. Although Holstein steer carcasses had less fat trim than Brahman-crossbred steers mixed-Exotic heifers, this advantage was largely offset by their higher percentage of bone. Loin steaks from carcasses of Charolais crossbred bulls, Holstein, mixed-Exotic heifers were comparable (P > 0·05)with those of Hereford-Angus steers for shear force and sensory panel tenderness ratings. However, loin steaks from carcasses of Brahman-crossbred steers had significantly higher (P < 0·05) shear force values (least tender) and lower (P < 0·05) tenderness and overall palatability ratings. No diffeerences (P > 0·05) were found for flavor desirability of loin steaks among any of the groups. For bottom round steaks, Hereford-Angus steers received the highest palatability ratings while those from Holstein steers received the lowest palatability ratings.

Construct validity of the marital communication inventory.

The Marital Communication Inventory (MCI) is an extremely popular self-report measure of marital communication that has been used in over 65 dissertations and empirical articles since 1970, including several recent clinical reports that used the MCI as a principal outcome measure. However, contrary to its treatment in the clinical literature as a unidimensional, valid measure of treatment outcome, the MCI appears to be a multidimensional instrument, whose primary dimension may not be a specific style or method of communication. Using a canonical correlation analysis of data from over 200 midwestern wives, we compared MCI subscales with subscales from an abbreviated version of the Barrett-Lennard Relationship Inventory (RI). Results supported the hypothesis that the primary dimension of the MCI is more closely associated with positive regard than with the more specific communication dimensions of either empathy or congruence as measured by the RI. Future clinical research in the improvement of marital communication should use the MCI in a much more careful way in order to provide the most valid outcome data.

Influence of Electrical Stimulation on Palatability of Hot-Boned, Pre-Rigor and Cold-Boned, Post-Rigor Frozen Beef Roasts 1.

The effects of electrical stimulation on palatability of hot-boned, pre-rigor and cold-boned, post-rigor frozen beef roasts were studied by use of 16 steer carcasses. Both sides of 8 carcasses were electrically stimulated (1.5 amps; 100 - 1 s impulses); sides from the other 8 carcasses served as controls. One side of each carcass was hot-boned and the remaining side was boned following a 48 h chill (2 C). Roasts from the rump portion (anterior one-fourth) of the biceps femoris muscle were vacuum-packaged and frozen (-20 C). Following a 48-h thaw (0 C). roasts were weighed, measured for length, width and depth, seasoned, placed in cooking bags and roasted to 62.5 C. Cooking losses were less (P<0.06) for hot-boned, pre-rigor frozen vs. cold-boned, post-rigor frozen roasts. Raw pH (post-freezing) was lower (P<0.01) for hot-boned than cold-boned roasts. No differences (P>0.05) were noted in shape changes for stimulation or chilling. Using triangle tests, untrained panel members were able to distinguish controls from electrically stimulated roasts and hot-boned from cold-boned roasts when served as thick (1.27 cm) or thin (2 mm) samples. Thick and thin samples of cold-boned roasts were preferred over hot-boned roasts. For roasts from carcasses that were not electrically stimulated, 62.6% preferred cold-boned roasts for thick samples while 61.4% preferred cold-boned roasts for thin samples. Cold-boned roasts from electrically stimulated carcasses were preferred over hot-boned roasts, 56.5% (thick) vs. 51.5% (thin). Warner-Bratzler shear force results indicated that hot-boned, control roasts required 79% more shear force than cold-boned roasts, but roasts from electrically stimulated carcasses required 14% more force to shear hot-boned than cold-boned roasts.