Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical ...responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy.
A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline.
At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253).
Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.
AIMS: To evaluate the effects of treating barley grain with lactic acid (LA) and heat on postprandial dynamics of 19 microbial taxa and fermentation in the rumen of dairy cows. METHODS AND RESULTS: ...This study was designed as a double 3 × 3 Latin square with six rumen‐cannulated cows and three diets either containing untreated control barley or barley treated with 1% LA and 1% LA and heat (LAH, 55°C). Microbial populations, pH and volatile fatty acids were assessed in rumen liquid and solids during the postprandial period. Propionate increased and butyrate decreased in rumen solids of cows fed LA and LAH treated barley compared to the control barley. The LA but not LAH treatment depressed Fibrobacter succinogenes in rumen liquid and solids, whereas the opposite effect was observed for Ruminococcus albus in both fractions and Ruminococcus flavefaciens in rumen solids. LA promoted Ruminobacter amylophilus with the effect being more pronounced with LAH. The Lactobacillus group and Megasphaera elsdenii increased in both fractions with LA but not with LAH. CONCLUSIONS: LA and LAH treatment of barley differently altered ruminal abundance of certain bacterial taxa and fungi and increased propionate fermentation in rumen solids, whereby LA and LAH effects were consistent and mostly independent of the rumen fraction and time after barley feeding. SIGNIFICANCE AND IMPACT OF THE STUDY: Results provided evidence that LA and LAH treatment of barley can enhance rumen propionate fermentation without adversely affecting rumen pH. As propionate is the major contributor to gluconeogenesis in ruminants, the present barley treatment may have practical application to enhance energy supply in dairy cows.
Over saturation behavior of SiPMs at high photon exposure Gruber, L.; Brunner, S.E.; Marton, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2014, Letnik:
737
Journal Article
Recenzirano
Odprti dostop
Several types of Silicon Photomultipliers were exposed to short pulsed laser light (~30ps FWHM) with its intensity varying from single photon to well above the number of microcells of the device. We ...observed a significant deviation of the output of SiPMs from the expected behavior although such response curve is considered to be rather trivial. We also noticed that the output exceeds the maximum expected pulse height, which should be defined as the total number of pixels times the single photon pulse height. At the highest light intensity (~500 times the number of pixels) that we tested, the signal output reached up to twice the maximum theoretical pulse height, and still did not fully saturate.
Assisted living (AL) residents with dementia require assistance with activities of daily living, encounter limited opportunities to engage in physical activity, and often exhibit challenging ...behavioral symptoms. The Function Focused Care Intervention for the Cognitively Impaired (FFC-CI) teaches and motivates direct care workers (DCWs) to engage residents with dementia in activities that optimize function and activity while minimizing behavioral symptoms. The purpose of this study was to test the impact of FFC-CI on function, physical activity, behavior, and falls.
A cluster-randomized trial included 96 residents with dementia and 76 DCWs from 4 ALs. Generalized estimating equations were used to evaluate outcomes at 3 and 6 months.
There were no treatment by time differences with regard to resident behavior, mood, counts of physical activity based on actigraphy, falls, and function. There were significant increases in physical activity based on kilocalories burned (p = .001), time spent in physical activity based on survey results (p = .001), and time spent in repetitive behaviors, such as wandering (p = .01) among the control group over time. There were no treatment by time differences with regard to DCW beliefs, knowledge, or performance of FFC, except for less decline in job satisfaction among the treatment group (p = .002). Treatment fidelity with regard to delivery and receipt were poor due to high staff attrition in the treatment group (46% vs. 16%) and limited site support.
The findings from this study can be used to adapt future FFC intervention studies to improve treatment fidelity and optimize intervention efficacy.
Relationships between behavioral and physiological symptoms of preslaughter stress and LM Warner-Bratzler shear force (WBSF) were investigated using Bos taurus steers (n = 79) and heifers (n = 77). ...Measurements of heart rate, respiration rate, rectal temperature, and concentrations of serum cortisol and plasma epinephrine were used as indicators of stress associated with physical handling and chute restraint, whereas concentrations of cortisol, glucose, lactate, and creatine kinase in blood samples obtained at exsanguination were measured to reflect physiological reactions of animals to transportation stress. Increased plasma epinephrine concentration, indicative of acute handling stress, was associated with elevated heart rate (r = 0.42, P < 0.001) and rectal temperature (r = 0.34, P < 0.001) during restraint, increased plasma lactate (r = 0.22, P = 0.006) and serum creatine kinase (r = 0.28, P < 0.001) concentrations at slaughter, and greater LM WBSF (r = 0.22, P = 0.006). Plasma lactate concentration at slaughter, which reflected an adrenergic stress response to transportation, was associated with lesser final LM pH (r = -0.30, P < 0.001) and greater LM WBSF (r = 0.26, P = 0.002). Categorical analyses of chute and posttransportation behavior scores (calm vs. restless vs. nervous) showed that cattle exhibiting adverse behavioral reactions to handling and chute restraint had increased (P < 0.05) values for plasma epinephrine concentration, heart rate, and rectal temperature during chute restraint, elevated (P < 0.05) plasma lactate concentration at slaughter, and increased (P < 0.05) LM WBSF. In addition, cattle showing behavioral symptoms of stress after transportation had greater (P < 0.05) plasma glucose and lactate concentrations at slaughter and produced LM steaks that were 0.34 kg tougher (P < 0.05) when compared with calm cattle. No carcasses were identified as dark cutters, and LM pH did not differ (P > 0.05) among behavior categories. Grouping cattle according to differences in plasma lactate concentration categorized them according to mean differences in LM WBSF. Moreover, steaks from cattle with the greatest plasma lactate concentrations at slaughter (91st to 100th percentile) had a delayed response to aging that persisted until 14 d postmortem. Stress-induced differences in LM tenderness observed in this study were independent of differences in muscle pH.
This study is part of a larger project whose overall objective was to evaluate the possibilities for genetic improvement of efficiency in Austrian dairy cattle. In 2014, a 1-yr data collection was ...carried out. Data from 6,519 cows kept on 161 farms were recorded. In addition to routinely recorded data (e.g., milk yield, fertility, disease data), data of novel traits e.g., body weight (BW), body condition score (BCS), lameness score, body measurements and individual feeding information and feed quality were recorded on each test-day. The specific objective of this study was to estimate genetic parameters for efficiency (related) traits and to investigate their relationships with BCS and lameness in Austrian Fleckvieh, Brown Swiss, and Holstein cows. The following efficiency (related) traits were considered: energy-corrected milk (ECM), BW, dry matter intake (DMI), energy intake (INEL), ratio of milk output to metabolic BW (ECM/BW0.75), ratio of milk output to DMI (ECM/DMI), and ratio of milk energy output to total energy intake (LE/INEL, LE = energy in milk). For Fleckvieh, the heritability estimates of the efficiency (related) traits ranged from 0.11 for LE/INEL to 0.44 for BW. Heritabilities for BCS and lameness were 0.19 and 0.07, respectively. Repeatabilities were high and ranged from 0.30 for LE/INEL to 0.83 for BW. Heritability estimates were generally lower for Brown Swiss and Holstein, but repeatabilities were in the same range as for Fleckvieh. In all 3 breeds, more-efficient cows were found to have a higher milk yield, lower BW, slightly higher DMI, and lower BCS. Higher efficiency was associated with slightly fewer lameness problems, most likely due to the lower BW (especially in Fleckvieh) and higher DMI of the more-efficient cows. Body weight and BCS were positively correlated. Therefore, when selecting for a lower BW, BCS is required as additional information because, otherwise, no distinction between large animals with low BCS and smaller animals with normal BCS would be possible.
The present study aimed to investigate the long-term effect of feeding barley grain steeped in lactic acid (La) with or without thermal treatment on reticuloruminal pH dynamics and metabolic activity ...of the liver in 12 primiparous and 18 multiparous early-lactating dairy cows. All cows were included on d 21 postpartum and sampled until d 90 postpartum. Cows were fed a diet based on differently processed ground barley grain: untreated grain (control diet, CON), or grain treated with 1% La alone for 24 h before feeding (La), or with an additional oven-heating at 55°C for 12 h (LaH). The reticuloruminal pH and temperature were measured via indwelling sensors that allowed for continuous (every 10min) and long-term measurement from d 21 to 80 postpartum. Blood samples were taken on d 21, 40, and 90 of lactation and analyzed for liver enzymes aspartate aminotransferase (AST), gamma-glutamyltransferase, and glutamate dehydrogenase, as well as bilirubin, bile acids, and serum amyloid A. Dry matter intake was higher in multiparous cows (20.7±0.27 kg/d) compared with primiparous cows (18.2±0.33 kg/d), but was not affected by dietary treatment. Overall, the relatively short duration (51±5min/d) of reticuloruminal pH <5.8 suggests low risk of subacute ruminal acidosis throughout the experiment. Results indicated that La treatment of barley, with or without heat, lowered the time duration of pH <5.8 compared with CON, but only in primiparous cows (from 118±13 to 46±11 and 25±11min/d for CON, La, and LaH, respectively). In multiparous cows, the opposite effect of feeding the La-treated barley on time duration of pH <5.8 (11±8 vs. 46±9 vs. 57±9min/d for CON, La, and LaH, respectively) was observed. Multiparous cows generally showed higher pH readings and shorter periods in which the ruminal pH dropped below the threshold of pH 5.8. The reticuloruminal temperature was not affected by dietary treatment, whereas parity affected the time duration of reticuloruminal temperature >39.5°C, being 60±19min/d shorter in primiparous cows. The measured activities of the liver enzymes AST, gamma-glutamyltransferase, and glutamate dehydrogenase, as well as bilirubin, bile acids, and the acute phase protein serum amyloid A, were not affected by grain feeding. Additionally, only one small effect of parity on investigated serum variables was noticed, showing slightly but significantly higher values of AST in multiparous (80.5±1.4 U/L) compared with primiparous cows (76.0±1.7 U/L). In conclusion, our results indicate greater risk for primiparous cows to develop subacute ruminal acidosis-like conditions during early lactation than multiparous cows. The study also suggests limited benefits of feeding processed barley grain with La with or without thermal treatment to modulate ruminal tolerance of grain feeding, whereby differing effects in primiparous cows were observed compared with multiparous cows.
Barrel time-of-flight detector for the PANDA experiment at FAIR Gruber, L.; Brunner, S.E.; Marton, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2016, Letnik:
824
Journal Article
Recenzirano
Odprti dostop
The barrel time-of-flight detector for the PANDA experiment at FAIR is foreseen as a Scintillator Tile (SciTil) Hodoscope based on several thousand small plastic scintillator tiles read-out with ...directly attached Silicon Photomultipliers (SiPMs). The main tasks of the system are an accurate determination of the time origin of particle tracks to avoid event mixing at high collision rates, relative time-of-flight measurements as well as particle identification in the low momentum regime. The main requirements are the use of a minimum material amount and a time resolution of σ<100ps. We have performed extensive optimization studies and prototype tests to prove the feasibility of the SciTil design and finalize the R&D phase. In a 2.7GeV/c proton beam at Forschungszentrum Jülich a time resolution of about 80ps has been achieved using SiPMs from KETEK and Hamamatsu with an active area of 3×3mm2. Employing the Digital Photon Counter from Philips a time resolution of about 30ps has been reached.
Phthalates have long been used as plasticizers to soften plastic products and, thus, are ubiquitous in modern life. As part of the Bavarian Monitoring of Breast Milk (BAMBI), we aimed to characterize ...the exposure of infants to phthalates in Germany. Overall, 15 phthalates, including di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), di-isobutyl phthalate (DiBP), di-isononyl phthalate (DiNP), three primary metabolites of DEHP mono-(2-ethylhexyl) phthalate (MEHP), mono-isobutyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP), and two secondary metabolites of DEHP were analyzed in 78 breast milk samples.
We found median concentrations of 3.9
ng/g for DEHP, 0.8
ng/g for DnBP, and 1.2
ng/g for DiBP, while other parent phthalates were found in only some or none of the samples at levels above the limit of quantitation. In infant formula (n
=
4) we observed mean values of 19.7
ng/g (DEHP), 3.8
ng/g (DnBP), and 3.6
ng/g (DiBP). For MEHP, MiBP, and MnBP, the median values in breast milk were 2.3
μg/l, 11.8
μg/l, and 2.1
μg/l, respectively. The secondary metabolites were not detected in any samples.
Using median and 95th percentile values, we estimated an “average” and “high” daily intake for an exclusively breast-fed infant of 0.6
μg/kg body weight (b.w.) and 2.1
μg/kg b.w., respectively, for DEHP, 0.1
μg/kg b.w. and 0.5
μg/kg b.w. for DnBP, and 0.2
μg/kg b.w. and 0.7
μg/kg b.w. for DiBP. For DiNP, intake values were 3.2
μg/kg b.w. and 6.4
μg/kg b.w., respectively, if all values in milk were set half of the detection limit or the detection limit.
The above-mentioned “average” and “high” intake values corresponded to only about 2% to 7%, respectively, of the recommended tolerable daily intake. Thus, it is not likely that an infant's exposure to phthalates from breast milk poses any significant health risk. Nevertheless, other sources of phthalates in this vulnerable phase have to be considered. Moreover, it should be noted that for infants nourished with formula, phthalate intake is of the same magnitude or slightly higher (DEHP) than for exclusively breast-fed infants.
►Phthalates and their metabolites could be detected in breast milk ►Today, the intake of phthalates is low ►Infant's exposure to phthalates from breast milk poses no health risk