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Condensed tannins (CT) are plant polyphenols that can affect feed digestibility and are potentially able to reduce enteric CH 4 emissions in ruminants. In this in vivo trial with 8 lactating goats, we investigated the effects of 4 levels of inclusion of a commercial CT extract from quebracho (0%, 2%, 4%, and 6% on dry matter basis; CON, Q2, Q4, and Q6, respectively). The experimental design was a repeated 4 × 4 Latin square with 28-d periods (24 d of diet adaptation and 4 d of sample collection) using metabolic cages and 4 open-circuit respiration chambers. The inclusion of CT in the diets did not affect the dry matter intake (DMI) but caused a linear decrease in diet digestibility, with reductions up to −11% for dry matter, −21% for crude protein (CP), −23% for α-amylase- and sodium sulfite-treated neutral detergent fiber corrected for insoluble ash (aNDFom), and −13% for gross energy, when comparing the Q6 and CON diets. However, ruminal total volatile fatty acids (VFA) concentration was not affected by CT, although there were changes in VFA proportions. Milk yield was highest for Q4 (3,371 g/d) and lowest for Q6 (3,066 g/d). In terms of milk composition, CT induced a linear reduction of fat and CP concentrations. The reduction in CP digestibility resulted in a linear reduction in the milk urea level, up to −37% with Q6. Positively, CT linearly reduced the somatic cells count expressed as linear score. The feed efficiency was linearly decreased by CT inclusion. Furthermore, a shift from urinary to fecal nitrogen excretion was observed with CT. The retained nitrogen was always negative (on average −1.93 g/d). The CH 4 yield (on average 19.2 g of CH 4 /kg DMI) was linearly reduced by CT inclusion, up to −18% with Q6. Regarding the CH 4 intensity, CT induced a linear reduction when expressed per kilogram of milk, but not per kilogram of fat and protein-corrected milk. Moreover, the CH 4 production per kilogram of digestible aNDFom was linearly increased by CT. The metabolizable energy intake (MEI) was not affected by the treatments, but the metabolizability (q = MEI/gross energy intake) was reduced as CT inclusion increased. From the results of the present study, it turned out that CT have a negative impact on feed digestibility and feed use efficiency. Condensed tannins can lower CH 4 emissions from ruminants; however, the main mechanism of action is likely the decrease in feed digestibility. Furthermore, CT did not improve the N use efficiency. According to these findings, the positive environmental impacts of CT are only related to the shift from urinary to fecal N excretion. [ABSTRACT FROM AUTHOR]

Eight lactating Italian Friesian cows were housed in individual respiration chambers in a repeated Latin square design to determine their dry matter intake (DMI) and their milk and methane production, as well as to collect the total feces and urine to determine the N and energy balances. Four diets, based on the following forages (% of dry matter, DM), were tested: corn silage (CS, 49.3), alfalfa silage (AS, 26.8), wheat silage (WS, 20.0), and a typical hay-based Parmigiano Reggiano cheese production diet (PR, 25.3 of both alfalfa and Italian ryegrass hay). The greatest DMI was observed for cows fed PR (23.4 vs. 20.7 kg/d, the average of the other 3 diets). The DM digestibility was lower for PR (64.5 vs. 71.7%, the average of the other diets). The highest ash-free neutral detergent fiber digestibility values were obtained for CS (50.7%) and AS (47.4%). In the present study, no differences in milk production were observed between diets, although PR showed a higher milk yield trend. The highest milk urea N concentration (mg/dL) was found for the cows fed the WS diet (13.8), and the lowest was observed for the cows fed AS (9.24). The highest milk urea N concentration for the cows fed WS was also correlated with the highest urinary N excretion (g/d), which was found for the cows fed that same diet (189 vs. 147 on average for the other diets). The protein digestibility was higher for the cows fed the CS and WS diets (on average 68.5%) than for the cows fed AS and PR (on average 57.0%); dietary soybean inclusion was higher for CS and WS than for AS and PR. The rumen fermentation pattern was affected by the diet; the cows fed the PR diet showed a higher rumen pH and decreased propionate production than those fed CS, due to the lower nonfiber carbohydrate content and higher ash-free neutral detergent fiber content of the PR diet than the CS diet. Feeding cows with PR diet increased the acetate:propionate ratio in comparison with the CS diet (3.30 vs. 2.44 for PR and CS, respectively). Cows fed the PR diet produced a greater daily amount of methane and had a greater methane energy loss (% of digestible energy intake) than those fed the CS diet (413 vs. 378 g/d and 8.67 vs. 7.70%), but no differences were observed when methane was expressed as grams per kilogram of DMI or grams per kilogram of milk. The PR diet resulted in a smaller net energy for lactation content than the CS diet (1.36 vs. 1.70 Mcal/kg of DM for the PR and CS diets, respectively). Overall, our research suggests that a satisfactory milk production can be attained by including different high-quality forages in balanced diets without any negative effect on milk production or on the methane emissions per kilogram of milk. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of diets with different starch concentrations and fish oil (FO) supplementation on lactation performance, in vivo total-tract nutrient digestibility, N balance, and methane (CH4) emissions in lactating dairy cows. The experiment was conducted as a 4 x 4 Latin square design with a 2 x 2 factorial arrangement: 2 concentrations of dietary starch [low vs. high: 23.7 and 27.7% on a dry matter (DM) basis; neutral detergent fiber/ starch ratios: 1.47 and 1.12], the presence or absence of FO supplement (0.80% on a DM basis), and their interaction were evaluated. Four Italian Friesian cows were fed 1 of the following 4 diets in 4 consecutive 26-d periods: (1) low starch (LS), (2) low starch plus FO (LSO), (3) high starch (HS), and (4) high starch plus FO (HSO). The diets contained the same amount of forages (corn silage, alfalfa and meadow hays). The starch concentration was balanced using different proportions of corn meal and soybean hulls. The cows were housed in metabolic stalls inside open-circuit respiration chambers to allow measurement of CH4 emission and the collection of separate urine and feces. No differences among treatments were observed for DM intake. We observed a trend for FO to increase milk yield: 29.2 and 27.5 kg/d, on average, for diets with and without FO, respectively. Milk fat was affected by the interaction between dietary starch and FO: milk fat decreased only in the HSO diet. Energy-corrected milk (ECM) was affected by the interaction between starch and FO, with a positive effect of FO on the LS diet. Fish oil supplementation decreased the n-6:n-3 ratio of milk polyunsaturated fatty acids. High-starch diets negatively influenced all digestibility parameters measured except starch, whereas FO improved neutral detergent fiber digestibility (41.9 vs. 46.1% for diets without and with FO, respectively, and ether extract digestibility (53.7 vs. 67.1% for diets without and with FO, respectively). We observed a trend for lower CH4 emission (g/d) and intensity (g/kg of milk) with the high-starch diets compared with the low-starch diets: 396 versus 415 g/d on average, respectively, and 14.1 versus 14.9 g/kg of milk, respectively. Methane intensity per kilogram of ECM was affected by the interaction between starch and FO, with a positive effect of FO for the LS diet: 14.5 versus 13.3 g of CH4/kg of ECM for LS and LSO diets, respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate in high producing dairy goats the relationship between milk urea level (MUL) and diet composition, milk yield (MY), intestinal digestible protein (PDI) balance, milk N efficiency and urinary N (UN) excretion. Twenty-one mean treatment data, derived from thirteen diets tested in five experiments conducted on goats kept in metabolic cages to collect separately feces and urine, were used. Diets, orts and milk were analyzed for chemical composition; urine was analyzed for N content. PDI with N as limiting factor for rumen microbial growth (PDIN) was calculated according to the French system as well as PDI requirements. Relationships were developed using regression analysis based on mixed models that account for between-experiment variation. There were significant relationships between MUL (mg/dL) and dietary crude protein (CP) (g/kg DM): MUL = −45.3 + 0.484 CP ( R 2 = 0.914), and between MUL and PDIN balance (%): MUL = 22.9 + 0.347 PDIN balance ( R 2 = 0.917). The relationship between MUL and MY was not significant. Milk N efficiency resulted negatively related with MUL and positively related with MY (kg/d): milk N efficiency = 33.8–0.38 MUL + 2.58 MY ( R 2 = 0.869). UN excretion (g/d) was positively related with MUL:UN excretion (g/d) = 14.4 + 0.348 MUL ( R 2 = 0.713). The urea concentration of goat's milk can be utilized for a finer tuning of protein feeding, in order to improve milk N efficiency and reduce urinary N excretion. [ABSTRACT FROM AUTHOR]

The aim was to evaluate 2 levels of dietary inclusion of chopped whole-ear corn silage (WECS) on energy and nutrient utilization, growth, and slaughter performances of heavy pigs. Two in vivo experiments were conducted to determine digestibility and metabolic utilization of WECS using 18 barrows weighing 118 ± 8 kg BW on average, metabolic cages and respiration chambers (Exp. 1), and the effect of WECS on the growth performance and carcass traits on 42 barrows from 90 to 170 kg BW (Exp. 2). In both experiments, pigs were fed 3 experimental diets: a control diet (CON) containing cereal meals, extracted soybean meal, and wheat bran (80%, 9%, and 8% of DM, respectively) and 2 diets containing 15% (15WECS) or 30% WECS (30WECS) on a DM basis in place of wheat bran and corn meal. The diets were prepared daily by mixing the WECS to a suitable compound feed. Feed intake was always restricted to allow a daily DMI of 7.2% BW0.75 in Exp. 1 and from 8.0% to 6.5% BW0 75 in Exp. 2. Diets had similar NDF contents (15.2% to 15.8% of DM), and WECS inclusion resulted in a slight reduction in CP content (from 14.0% to 13.6% of DM) and a considerable decrease in P content (from 0.47% to 0.30% of DM). Digestibility of OM, CP, and fat was similar among diets, whereas P digestibility was lower (P < 0.05) for the 30WECS diet (33.5%) in comparison with the CON and 15WECS diets (45.5% and 44.1%, respectively). Nitrogen lost in feces and urine and N retained were not different among diets, whereas P retained decreased with the increase of WECS (5.4, 3.7, and 2.2 g/d for the CON, 15WECS, and 30WECS diets, respectively; P < 0.05). No difference among diets was observed for energy balance. The WECS contained 13.48 MJ ME and 9.39 MJ NE/kg DM. In Exp. 2, feed intake was not depressed by WECS inclusion, and the ADG for the whole experiment was not different among dietary treatments (from 737 to 774 g/d). Fecal pH was lower (P < 0.05) for the WECS diets than the control diet (7.10 and 7.00 vs. 7.40) and for the sampling at 150 kg BW than that at 130 and 110 kg BW (6.96 vs. 7.29 and 7.24). At slaughter, lean percentage in the carcass was lower in the 30WECS diet than those of the other 2 diets (46.8% vs. 48.3% and 48.6%, P = 0.05). The overall experimental data obtained in both trials indicate that substitution of wheat bran and com meal for WECS (up to 30% of DM) does not affect, with the exception of P utilization and carcass leanness, energy and nutrient utilization and performance of heavy pigs in the last phase of growing. [ABSTRACT FROM AUTHOR]

Total mixed rations containing corn (CS), whole plant grain sorghum (WPGS), or forage sorghum (FS) silages were fed to 6 primiparous Italian Friesian cows to determine the effects on lactation performance, nutrient digestibility, and N balance. Furthermore, the relationship between in vivo total-tract neutral detergent fiber (NDF) digestibility (ttNDFD) and the ttNDFD derived by the Cornell Net Carbohydrate and Protein System (CNCPS) model was assessed. Cows were assigned to 1 of 3 diets in a replicated 3 x 3 Latin square with 28-d periods. The experimental treatment was silage type and 3 different silages were included in the diets. The diets were formulated to be iso-NDF. Accordingly, each diet was formulated to contain 41.5% CS silage, 36.7% WPGS silage, or 28.0% FS silage, on a DM basis. Starch content was balanced by adding the appropriate amount of corn meal. Separate collection of total urine and feces was performed. Dietary forages were analyzed for in vitro NDF digestibility (6 and 24 h of incubation) to predict fiber digestion rate with 2 NDF pools (digestible and indigestible). Rumen digestibility of the potentially digestible NDF pool was predicted using CNCPS version 6.1, using the in vitro forage fiber digestion rate. The ttNDFD was predicted assuming that intestinal digestibility of the NDF amount escaping rumen digestion was 20%, according to the CNCPS model. Dry matter intake was decreased by approximately 1.8 kg/d in cows fed the FS diet compared with the other diets, probably for the greater particle size of FS diet. Hence, milk yield (kg/d) was lowest for FS (23.6), intermediate for WPGS (24.6), and highest for the CS diet (25.4). Milk urea N (mg/dL) was highest for FS (12.9), intermediate for WPGS (11.9), and lowest for CS (10.7) diet. In vivo ttNDFD (%) was 51.4 (CS), 48.6 (WPGS), and 54.1 (FS); this was probably due to a higher retention time of FS diet in the rumen rather than to a better quality of the FS silage, as confirmed by in situ and in vitro results. Urinary N excretion (% N intake) was highest for FS (31.8), intermediate for WPGS (29.3), and lowest for the CS (27.5) diet. The predicted ttNDFD (37.7, 36.3, and 39.5% for CS, WPGS, and FS, respectively) were lower than the in vivo results. Providing an adequate starch supplementation, whole plant grain sorghum silage can replace corn silage in dairy cows TMR. Forage sorghum silage had rumen NDF digestibility comparable to the other silages; however, it had a negative effect on dry matter intake and milk production, probably due to an inadequate effect of processing. [ABSTRACT FROM AUTHOR]

Abstract: An experiment was conducted to determine the effects of dietary fibre and protein contents and addition of bentonite on performance, nitrogen (N) balance and ammonia emission of heavy pigs from 80 to 170kg bodyweight. Pigs were fed 4 diets differing in the contents (g/kg as fed) of neutral detergent fibre (aNDFom) and crude protein (CP): 114 and 120 (diet C, control), 193 and 122 (diet HF, high fibre), 176 and 98 (diet HFLP, high fibre and low protein), and 175 and 99 (diet HFLPB, high fibre and low protein plus 10g bentonite/kg) for aNDFom and CP, respectively. Eighty pigs were randomly allotted to the 4 dietary treatments (4 pens for each treatment and 5pigs per pen). In addition, 6 pigs from each treatment were placed in individual metabolic cages for 7 days to determine total tract apparent digestibility (TTAD), N balance and ammonia emission from slurry. Dietary treatment did not affect average daily gain, feed conversion ratio and slaughter performance. The inclusion of fibre reduced TTAD of dry matter (P<0.001), organic matter (P<0.001), CP (P=0.026) and energy (P<0.001). Pigs fed the high fibre diets excreted more N in faeces than pigs fed the C diet (P=0.015). Urinary N was lower (P=0.007) for the low protein diets (17.8g/day, for both) compared to C (25.8g/day) and HF diets (23.8g/day). Nitrogen excretion was reduced by approximately 8.0% for each 10g/kg of dietary CP reduction. The pH values of slurries were not affected by diet. At the end of the monitoring period (14 days) pH was lower (P=0.046) for the low protein diets (8.26 for HFLP; 8.28 for HFLPB) in comparison with the C diet (8.82). Ammonia cumulative emission measured for 14 days was not affected by diet. Significant differences (P=0.048) were observed between diets C vs HF, HFLP and HFLPB when emission was expressed as the ratio between ammonia N emitted and initial N. It is concluded that increasing the fibre content of the diet together with a decrease of the protein content reduced N excretion without jeopardizing performance of heavy pigs. The inclusion of bentonite did not affect any of the traits studied. [Copyright &y& Elsevier]

This study evaluated the middle ear microbial flora and antimicrobial susceptibility patterns from dogs with otitis media. Antimicrobial susceptibility patterns were obtained on 164 micro-organisms from 107 ears of 82 dogs with otitis media that presented to Louisiana State University over a 12-year period. The most common micro-organisms isolated were Staphylococcus intermedius (26.8%), Pseudomonas aeruginosa (23.2%), β-haemolytic streptococcus (12.8%), Proteus spp. (11.0%) and Staphylococcus epidermidis (8.5%). Antimicrobial susceptibility testing was performed on all isolates employing the disk diffusion method (Kirby-Bauer). Minimum inhibitory concentration (MIC) testing for enrofloxacin and ciprofloxacin was performed on 10 of the 18 P. aeruginosa isolates found to be resistant to enrofloxacin on Kirby-Bauer. Of these isolates, 6 (60%) were susceptible, 1 (10%) was intermediate and 3 (30%) were resistant to enrofloxacin. Eight of these isolates (80%) were susceptible to ciprofloxacin, 1 (10%) showed intermediate susceptibility and 1 (10%) was resistant. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and standardize a protocol for intradermal skin testing in birds. Forty clinically normal Hispaniolan Amazon parrots were anaesthetized and tested by intradermal injection with 0.02 mL of phosphate-buffered saline, histamine phosphate, compound 48/80, codeine phosphate, deionized water, antiavian IgG and rabbit serum. Injection sites were evaluated at 5, 10 and 15 min, 4–6, 24 and 48 h following injection using callipers to measure the diameter of the wheals. A second intradermal skin test was repeated in 20 birds with 0.03 mL of saline, compound 48/80 and codeine phosphate. This study provides the basis for an appropriate protocol for intradermal skin testing in parrots, including recommended site (proventer region), volume of injection (0.02 mL), negative control (saline), positive control (codeine phosphate 1 : 100 000 w/v) and optimum reading time (5 min). Further study to establish appropriate dosages for test antigen will be required. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Automated measurements of the ratio of concentrations of methane and carbon dioxide, [CH 4 ]:[CO 2 ], in breath from individual animals (the so-called "sniffer technique") and estimated CO 2 production can be used to estimate CH 4 production, provided that CO 2 production can be reliably calculated. This would allow CH 4 production from individual cows to be estimated in large cohorts of cows, whereby ranking of cows according to their CH 4 production might become possible and their values could be used for breeding of low CH 4 -emitting animals. Estimates of CO 2 production are typically based on predictions of heat production, which can be calculated from body weight (BW), energy-corrected milk yield, and days of pregnancy. The objectives of the present study were to develop predictions of CO 2 production directly from milk production, dietary, and animal variables, and furthermore to develop different models to be used for different scenarios, depending on available data. An international dataset with 2,244 records from individual lactating cows including CO 2 production and associated traits, as dry matter intake (DMI), diet composition, BW, milk production and composition, days in milk, and days pregnant, was compiled to constitute the training dataset. Research location and experiment nested within research location were included as random intercepts. The method of CO 2 production measurement (respiration chamber [RC] or GreenFeed [GF]) was confounded with research location, and therefore excluded from the model. In total, 3 models were developed based on the current training dataset: model 1 ("best model"), where all significant traits were included; model 2 ("on-farm model"), where DMI was excluded; and model 3 ("reduced on-farm model"), where both DMI and BW were excluded. Evaluation on test dat sets with either RC data (n = 103), GF data without additives (n = 478), or GF data only including observations where nitrate, 3-nitrooxypropanol (3-NOP), or a combination of nitrate and 3-NOP were fed to the cows (GF+: n = 295), showed good precision of the 3 models, illustrated by low slope bias both in absolute values (−0.22 to 0.097) and in percentage (0.049 to 4.89) of mean square error (MSE). However, the mean bias (MB) indicated systematic overprediction and underprediction of CO 2 production when the models were evaluated on the GF and the RC test datasets, respectively. To address this bias, the 3 models were evaluated on a modified test dataset, where the CO 2 production (g/d) was adjusted by subtracting (where measurements were obtained by RC) or adding absolute MB (where measurements were obtained by GF) from evaluation of the specific model on RC, GF, and GF+ test datasets. With this modification, the absolute values of MB and MB as percentage of MSE became negligible. In conclusion, the 3 models were precise in predicting CO 2 production from lactating dairy cows. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate, through a survey conducted on commercial farms, the global warming potential (GWP) of different lactating cow total mixed rations (TMR) and to identify the best dietary strategies to increase feed efficiency (FE) and reduce enteric CH 4 emission. A total of 171 dairy herds were selected: data about dry matter intake (DMI), lactating cow TMR composition, and milk production and composition were provided by farmers. Diet GWP (kg of CO 2 equivalents; CO 2 eq) was calculated as sum of GWP (kg of CO 2 eq) of each included ingredient, considering inputs needed at field level, feed processing, and transport. For soybean solvent meal, land use change was included in the assessment. Enteric methane production (g/d) was estimated [using the equation CH 4 (g/d) = 2.54 + 19.14 × DMI] to calculate CH 4 emission for kilograms of fat- and protein-corrected milk (FPCM). The data set was analyzed by generalized linear model and logistic analysis using SAS 9.4 (SAS Institute Inc., Cary, NC). The frequency distribution showed wide variation among farms for GWP (kg of CO 2 eq) of TMR: approximately 25% of the surveyed farms showed a diet GWP of 15 kg of CO 2 eq, 20% showed a GWP of 13 kg of CO 2 eq, and 16.7% showed a GWP of 17 kg of CO 2 eq. The variation among farms was due to the feedstuffs used. Among feedstuffs, soybean meal (SBM) had the highest correlation with the GWP of the TMR as shown by the following equation: TMR GWP (kg of CO 2 eq) = 2.49 × kg of SBM + 6.9 (R2 = 0.547). Moreover, diets with inclusion of SBM >15% of dry matter (DM) did not result in higher milk production than diets with a lower inclusion of SBM (≤15%). Average daily milk production of cows was 29.8 [standard deviation (SD) 4.83] kg with fat and protein contents of 3.86% (SD 0.22) and 3.40% (SD 0.14), respectively. The average DMI (kg/d) of lactating cows was 22.3 (SD 2.23). Logistic analysis demonstrated that corn silage ≤30% of diet DM was associated with higher FE. Almost 50% of farms had an average value of 15.0 g of CH 4 /kg of FPCM and about 30% of farms had an average of 12.5 g of CH 4 /kg of FPCM. The results demonstrated that lower enteric CH 4 production was related to inclusion (% of diet DM) of ≤12% alfalfa hay and >30% corn silage. Diets with >34% neutral detergent fiber had higher CH 4 production (>14.0 g/kg of FPCM) than those with lower neutral detergent fiber content. In contrast, lower enteric CH 4 production (≤14.0 g/kg of FPCM) was related to diets characterized by net energy of lactation (NE L) >1.61 Mcal/kg and >4% ether extract. The variability in TMR GWP shows significant potential for reducing the GWP of a diet through choice and inclusion levels of ingredients (mainly SBM) and the possibility of decreasing methane enteric emission associated with milk production on a commercial scale. [ABSTRACT FROM AUTHOR]

Spontaneous avalanche to plasma begins in the core of an ellipsoidal Rydberg gas of nitric oxide. Ambipolar expansion of NO $^+$ draws energy from avalanche-heated electrons. Then, cycles of long-range resonant electron transfer from Rydberg molecules to ions equalize their relative velocities. This sequence of steps gives rise to a remarkable mechanics of self-assembly, in which the kinetic energy of initially formed hot electrons and ions drives an observed separation of plasma volumes. These dynamics adiabatically sequester energy in a reservoir of mass transport, starting a process that anneals separating volumes to form an apparent glass of strongly coupled ions and electrons. Short-time electron spectroscopy provides experimental evidence for complete ionization. The long lifetime of this system, particularly its stability with respect to recombination and neutral dissociation, suggests that this transformation affords a robust state of arrested relaxation, far from thermal equilibrium. We see this most directly in the excitation spectrum of transitions to states in the initially selected Rydberg series, detected as the long-lived signal that survives a flight time of $500\ \mathrm {\mu }$ s to reach an imaging detector. The initial density of electrons produced by prompt Penning ionization, which varies with the selected initial principal quantum number and density of the Rydberg gas, determines a balance between the rising density of ions and the falling density of Rydberg molecules. This Penning-regulated ion-Rydberg molecule balance appears necessary as a critical factor in achieving the long ultracold plasma lifetime to produce spectral features detected after very long delays. [ABSTRACT FROM AUTHOR]

Background:To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies.Methods:Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered.Results:Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13-85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29-6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18-8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11-6.30, P=0.028), white blood cell >11 000 μl−1 (HR: 2.59, 95% CI: 1.10-6.09, P=0.028) and haemoglobin<10 g dl−1 (HR: 3.1, 95% CI: 1.07-8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02).Conclusion:Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs. [ABSTRACT FROM AUTHOR]

Background: To investigate the incidence, risk factors and clinical implications of venous thromboembolism (VTE) in advanced cancer patients treated in phase I studies. Patients and methods: Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organization) Foundation between 2000 and 2010 in 15 experimental centers were considered for the study. Clinical data, including adverse events, were prospectively collected during the studies and retrospectively pooled for VTE analysis. Results: Data of 1415 patients were considered for analysis. Five hundred and twenty-six (37.2%) patients were males, and median age was 57.3 years (range: 13–85). Eighty-five percent of patients had metastatic disease, while the remaining had locally advanced irresectable disease. For 706 (49.9%) of the patients, the study treatment was with cytotoxic agent(s) only, for 314 with target therapy(ies) only, while the remaining patients received a target therapy in combination with a cytotoxic drug. Fifty-six (3.96%) patients who developed a VTE, almost all (89.3%) during the course of treatment, the remaining during the follow-up. At univariate analysis, the Khorana score, the combination of an antiangiogenic agent with a cytotoxic drug, and the time from first cancer diagnosis to study entry (as continuous variable) were associated with a statistically significant increase of VTE occurrence. The multivariate analysis confirmed only a statistically significant association for the Khorana score. The hazard ratio of VTE occurrence was 7.88 [95% confidence interval (CI) 2.86–21.70) and 2.74 (95% CI 1.27–5.92) times higher for the highest (≥3) and intermediate (1–2) scores as compared with score = 0. Conclusions: VTE is a relatively common complication among patients treated in the context of phase I studies. The Khorana score predicts VTE development and can be used to identify patients at high of VTE. [ABSTRACT FROM PUBLISHER]

The objective of this study was to determine if feeding roasted corn would improve production and nutrient utilization when supplemented to lactating cows fed 1 of 3 different alfalfa silages (AS). Forty-two lactating Holstein cows (6 fitted with ruminal cannulas) averaging 77 d in milk and 43 kg of milk/d pretrial were assigned to 2 cyclic changeover designs. Treatments were AS ensiled in bag, bunker, or O2-limiting tower silos and supplemented with ground shelled corn (GSC) or roasted GSC (RGSC). Silages were prepared from second-cutting alfalfa, field-wilted an average of 24 h, and ensiled over 2 d. Production and N utilization were evaluated in 36 cows during four 28-d periods, and ruminal fermentation was evaluated with 6 cows during five 21-d periods. Experimental diets contained 40% AS, 15% corn silage, and 35% of either GSC or RGSC on a dry matter basis. No significant interactions between AS and corn sources were detected for any production trait. Although the chemical composition of the 3 AS was similar, feeding AS from the O2-limited tower silo elicited positive production responses. Yields of 3.5% fat-corrected milk and fat were increased 1.7 kg/ d and 150 g/d, and milk fat content was increased 0.3% when cows were fed diets based on AS from the O2-limiting silo compared with the other 2 silages. The responses in milk fat were paralleled by an average increase in acid detergent fiber digestibility of 270 g/d for cows fed AS from the O2-limiting tower silo. However, ruminal concentrations of lipogenic volatile fatty acids were unchanged with AS source. Cows fed RGSC consumed 0.6 kg/d more dry matter and yielded 30 g/ d more protein and 50 g/d more lactose than cows fed GSC diets. There was no evidence of increased total tract digestibility of organic matter or starch, or reduced ruminal NH3 concentration, when feeding RGSC. Free amino acids increased, and isovalerate decreased in rumen fluid from cows fed RGSC diets. However, responses in production with roasted corn were mainly due to increased dry matter intake, which increased the supply of energy and nutrients available for synthesis of milk and milk components. [ABSTRACT FROM AUTHOR]

The aim of this study was to define the maximum tolerated dose (MTD) and the pharmacological profile of the paclitaxel analogue BMS-184476 given once every 3 weeks, or on days 1 and 8 every 3 weeks (d1&8), in combination with a fixed dose of 50 mg/m2 of Doxorubicin (Doxo) administered on day 1 of a 21-day cycle. Adult patients with advanced solid malignancies received escalating doses of BMS-184476 infused over 1 h after bolus Doxo. Pharmacokinetics (PK) of BMS-184476, Doxo and metabolites were investigated. The effect of BMS-184476 on doxorubicinol formation was studied in the cytosol from human myocardium. The MTD of 3-weekly BMS-184476 was 30 mg/m2. The MTD/recommended Phase II dose was 35 mg/m2/week (70 mg/m2 per cycle) in the d1&8 schedule. The dose-limiting toxicity was neutropenia for both schedules. Other toxicities were loss of appetite, asthenia, and mild, cumulative peripheral neuropathy. The objective response rate in 17 previously untreated or minimaletreated patients with breast cancer treated at 35 mg/m2/week of BMS-184476 was 59% (95% Confidence Interval (CI): 33–82%). Two of the 7 patients not responding to the study regimen later responded to Doxo and paclitaxel. Plasma disposition of BMS-184476 at 30, 35 and 40 mg/m2 was linear without evidence of a PK interaction with Doxo. In studies with cytosol from human myocardium, the formation of cardiotoxic doxorubicinol was not enhanced by BMS-184476. Dosing of BMS-184476 for 2 consecutive weeks allowed the administration of larger doses of the taxane with a promising antitumour activity in patients with untreated or minimally pretreated breast cancer. The higher than expected myelotoxicity of the 3-weekly schedule is unexplained by the investigated interactions. Lack of enhanced doxorubicinol formation in human myocardium is consistent with the cardiac safety of the regimen. [Copyright &y& Elsevier]

Background: Social networks have been recognised as an important factor for enhancing the health of people and communities. Bridging social capital, characterised by numerous and varied weak ties, exemplifies a particular type of network that can help people reach their goals and improve their health. This study seeks to contribute to the evidence base on the use of positive social networks for young people⇔tm)s health by exploring the importance of club participation in predicting the health and health-related behaviours of 15-year-old girls and boys across Europe and North America. Methods: Data are derived from a 2005-6 World Health Organization collaborative study, to establish the relationships between different types of club and a range of health outcomes (self-perceived health, wellbeing and symptoms) and health-related behaviours (smoking, drinking). Multi-level logistic regression was used to assess the independent effects of club participation by controlling for gender and socioeconomic position. Data were compared across six countries. Results: All the considered outcomes, both in terms of perceived health and wellbeing and health behaviours were associated with participation in formal associations. The associations are in the expected direction (participation corresponding to better health) except for some particular association types. Conclusions: Participation in formal associations seems supportive for good health and health behaviours in adolescence, and should be promoted in this age group. [ABSTRACT FROM AUTHOR]