Joint Solution for PET Image Segmentation, Denoising, and Partial Volume Correction

Publication date: Available online 28 March 2018
Source:Medical Image Analysis
Author(s): Ziyue Xu, Mingchen Gao, Georgios Z. Papadakis, Brian Luna, Sanjay Jain, Daniel J. Mollura, Ulas Bagci
Segmentation, denoising, and partial volume correction (PVC) are three major processes in the quantification of uptake regions in post-reconstruction PET images. These problems are conventionally addressed by independent steps. In this study, we hypothesize that these three processes are dependent; therefore, jointly solving them can provide optimal support for quantification of the PET images. To achieve this, we utilize interactions among these processes when designing solutions for each challenge. We also demonstrate that segmentation can help in denoising and PVC by locally constraining the smoothness and correction criteria. For denoising, we adapt generalized Anscombe transformation to Gaussianize the multiplicative noise followed by a new adaptive smoothing algorithm called regional mean denoising. For PVC, we propose a volume consistency-based iterative voxel-based correction algorithm in which denoised and delineated PET images guide the correction process during each iteration precisely. For PET image segmentation, we use affinity propagation (AP)-based iterative clustering method that helps the integration of PVC and denoising algorithms into the delineation process. Qualitative and quantitative results, obtained from phantoms, clinical, and pre-clinical data, show that the proposed framework provides an improved and joint solution for segmentation, denoising, and partial volume correction.

Graphical abstract

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SiSSR: Simultaneous Subdivision Surface Registration for the Quantification of Cardiac Function from Computed Tomography in Canines

Publication date: Available online 29 March 2018
Source:Medical Image Analysis
Author(s): Davis M. Vigneault, Amir Pourmorteza, Marvin L. Thomas, David A. Bluemke, J. Alison Noble
Recent improvements in cardiac computed tomography (CCT) allow for whole-heart functional studies to be acquired at low radiation dose ( < 2mSv) and high-temporal resolution ( < 100ms) in a single heart beat. Although the extraction of regional functional information from these images is of great clinical interest, there is a paucity of research into the quantification of regional function from CCT, contrasting with the large body of work in echocardiography and cardiac MR. Here we present the Simultaneous Subdivision Surface Registration (SiSSR) method: a fast, semi-automated image analysis pipeline for quantifying regional function from contrast-enhanced CCT. For each of thirteen adult male canines, we construct an anatomical reference mesh representing the left ventricular (LV) endocardium, obviating the need for a template mesh to be manually sculpted and initialized. We treat this generated mesh as a Loop subdivision surface, and adapt a technique previously described in the context of 3-D echocardiography to register these surfaces to the endocardium efficiently across all cardiac frames simultaneously. Although previous work performs the registration at a single resolution, we observe that subdivision surfaces naturally suggest a multiresolution approach, leading to faster convergence and avoiding local minima. We additionally make two notable changes to the cost function of the optimization, explicitly encouraging plausible biological motion and high mesh quality. Finally, we calculate an accepted functional metric for CCT from the registered surfaces, and compare our results to an alternate state-of-the-art CCT method.

Graphical abstract

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Comparing the performances of Magnetic Resonance Imaging size versus pharmacokinetic parameters to predict response to neoadjuvant chemotherapy and survival in breast cancer patients

Publication date: Available online 28 March 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Basak Dogan, Qing Yuan, Roland Bassett, Inanc Guvenc, Edward F. Jackson, Massimo Cristofanilli, Gary J. Whitman
PurposeTo compare the value of dynamic contrast-enhanced MRI (DCE-MRI)-pharmacokinetic (PK) parameters versus tumor volume in predicting breast cancer neoadjuvant chemotherapy response (NACR) and patient survival.Subjects and MethodsSixty-six patients with locally advanced breast cancer who underwent breast MRI monitoring of NACR were retrospectively analyzed. We compared baseline transfer constant (Ktrans), reflux rate contrast (kep), and extracellular extravascular volume fraction (ve) with the same parameters obtained at early post-chemotherapy MRI, and examined model-independent changes in time-intensity curves (maximum slope, contrast enhancement ratio, and IAUC90). Tumor size changes (tumor volume, single dimension, and RECIST) were also analyzed. The Spearman correlation test was used to assess the association between size and PK parameters, and regression analysis to assess the association with 5-year disease free survival.ResultsHigher ve values at baseline were associated with greater decreases in tumor size (P=0.008). Changes in Ktrans and IAUC90 were the strongest predictors of NACR. Changes in IAUC90 (P=0.04) and RECIST (P=0.003) were independently associated with pathological response. The only parameter significantly associated with 5-year survival was change in RECIST (P=0.001). However, there was a trend toward statistical significance for changes in ve and Ktrans, with greater changes associated with longer survival.ConclusionChanges in PK and DCE-MRI kinetic parameters may have a role in predicting NACR in breast tumors. While changes in Ktrans and IAUC90 are helpful in predicting NACR, they do not show significant association with survival. Early RECIST size change measured by MRI remains the strongest predictor of overall patient survival.



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Comparison of Natural Language Processing Rules-based and Machine-learning Systems to Identify Lumbar Spine Imaging Findings Related to Low Back Pain

Publication date: Available online 28 March 2018
Source:Academic Radiology
Author(s): W. Katherine Tan, Saeed Hassanpour, Patrick J. Heagerty, Sean D. Rundell, Pradeep Suri, Hannu T. Huhdanpaa, Kathryn James, David S. Carrell, Curtis P. Langlotz, Nancy L. Organ, Eric N. Meier, Karen J. Sherman, David F. Kallmes, Patrick H. Luetmer, Brent Griffith, David R. Nerenz, Jeffrey G. Jarvik
Rationale and ObjectivesTo evaluate a natural language processing (NLP) system built with open-source tools for identification of lumbar spine imaging findings related to low back pain on magnetic resonance and x-ray radiology reports from four health systems.Materials and MethodsWe used a limited data set (de-identified except for dates) sampled from lumbar spine imaging reports of a prospectively assembled cohort of adults. From N = 178,333 reports, we randomly selected N = 871 to form a reference-standard dataset, consisting of N = 413 x-ray reports and N = 458 MR reports. Using standardized criteria, four spine experts annotated the presence of 26 findings, where 71 reports were annotated by all four experts and 800 were each annotated by two experts. We calculated inter-rater agreement and finding prevalence from annotated data. We randomly split the annotated data into development (80%) and testing (20%) sets. We developed an NLP system from both rule-based and machine-learned models. We validated the system using accuracy metrics such as sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).ResultsThe multirater annotated dataset achieved inter-rater agreement of Cohen's kappa > 0.60 (substantial agreement) for 25 of 26 findings, with finding prevalence ranging from 3% to 89%. In the testing sample, rule-based and machine-learned predictions both had comparable average specificity (0.97 and 0.95, respectively). The machine-learned approach had a higher average sensitivity (0.94, compared to 0.83 for rules-based), and a higher overall AUC (0.98, compared to 0.90 for rules-based).ConclusionsOur NLP system performed well in identifying the 26 lumbar spine findings, as benchmarked by reference-standard annotation by medical experts. Machine-learned models provided substantial gains in model sensitivity with slight loss of specificity, and overall higher AUC.



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Essential oil and monensin affect ruminal fermentation and the protozoal population in continuous culture

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): D. Ye, S.K.R. Karnati, B. Wagner, J.L. Firkins, M.L. Eastridge, J.M. Aldrich
The interaction of monensin and essential oil was hypothesized to suppress protozoa and methane production while maintaining normal rumen function. The objective of this study was to determine the effects of feeding monensin (MON) and CinnaGar (CIN, a commercial blend of cinnamaldehyde and garlic oil) on ruminal fermentation characteristics. Continuous culture fermentors (n = 4) were maintained in 4 experimental periods in a 4 × 4 Latin square design. Four dietary treatments were arranged in a 2 × 2 factorial: (1) control diet, 37 g/d of dry matter (40 g/d at ∼92.5% dry matter) of a 50:50 forage:concentrate diet containing no additive; (2) MON at 11 g/909 kg of dry matter; (3) CIN at 0.0043% of dry matter; and (4) a combination of MON and CIN at the levels in (2) and (3). Treatment had no effects on protozoal populations, concentration of NH3N, total N flow of effluent, production of total volatile fatty acids, or flows of conjugated linoleic acid and total C18 fatty acids. The MON decreased acetate:propionate ratio and biohydrogenation of both total C18 and 18:1 cis-9 but increased protozoal generation time, concentration of peptide, and flow of 18:1 trans-11. The MON tended to decrease protozoal counts in effluent and flow of 18:0 but tended to increase propionate production. The CIN decreased true organic matter digestibility and protozoal N flow of effluent but increased nonammonia, nonmicrobial N flow. The CIN tended to decrease protozoal counts, microbial N flow, and neutral detergent fiber digestibility but tended to increase biohydrogenation of total C18, 18:2, and 18:3. The CIN tended to increase isovalerate production. The MON and CIN tended to interact for increased methane production and bacterial N flow. A second experiment was conducted to determine the effects of MON and CIN on protozoal nitrogen and cell volume in vitro. Four treatments included (1) control (feed only), (2) feed + 0.0043% dry matter CIN, (3) feed + 2.82 μM MON, and (4) feed + CIN + MON at the same levels as in (2) and (3). With no interactions, MON addition decreased percentage of protozoa that were motile and tended to decrease cell volume at 6 h. The CIN did not affect cell count or other indicators of motility or volume at either 3 or 6 h. Under the conditions of our study, we did not detect an additive response for MON and CIN to decrease protozoal counts or methane production. A 3-dimensional method is suggested to better estimate protozoal cell volume.



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Short communication: Pair housing dairy calves in modified calf hutches

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): L. Whalin, D.M. Weary, M.A.G. von Keyserlingk
The objective of this study was to test if body weight (BW) and starter intake increased and reaction to novelty decreased for preweaning Holstein heifer calves pair housed in modified hutches (n = 8 pairs) versus individually housed in a single hutch (n = 14 calves). Calves were alternately assigned to housing treatment at d 5 of age. Cross sucking was recorded in 5-min scans for 30 min after milk feeding once per week over 14 wk. Calf health and BW were measured weekly from birth until approximately 88 d. When calves were 60 d old they underwent a food neophobia test where they were exposed to a novel feed for the first time. Cross sucking was observed only 5 times (in 4 different pairs) over the entire milk-feeding period. Pair-housed calves ate more starter than individually housed calves [0.89 (0.72–1.08) vs. 0.48 (0.42–0.56) kg/d; median and confidence interval], these calves also consumed 2.6 times more novel feed in the neophobia test (150 ± 27 vs. 58 ± 20 g/30 min). We observed no effect of treatment on BW. We concluded that social housing in modified hutches promotes solid feed intake and decreases fearfulness in dairy calves.



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Veterinarians' attitudes toward antimicrobial use and selective dry cow treatment in the Netherlands

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): C.G.M. Scherpenzeel, I.M.G.A. Santman-Berends, T.J.G.M. Lam
In the Netherlands, regulations have been in place since 2008 to reduce the overall use of antimicrobials to mitigate antimicrobial resistance. As part of these regulations, a ban on the preventive use of antimicrobials, such as applying blanket dry cow treatment, was introduced and alternative measures such as selective dry cow treatment (SDCT) were implemented. Both farmers and veterinarians play an important role in implementing these measures and have a shared responsibility with respect to prudent antimicrobial use (AMU). The attitude of Dutch dairy veterinarians toward restricted AMU and toward SDCT is unknown, but a favorable attitude toward this approach seems crucial for successful implementation. In 2015, an online questionnaire was collected from 181 veterinarians that contained questions with regard to their attitude and behavior toward reduction of AMU and toward SDCT. Descriptive statistics were used to describe the data, and multivariable logistic regression models with a logit link function were applied to evaluate potential associations between veterinarians' attitudes toward AMU and SDCT and the rationale behind their mindset, based on positive and negative aspects of reduction in AMU. The veterinarians were divided into 3 groups based on their opinion on 4 statements with regard to AMU and SDCT: veterinarians with an unfavorable, a neutral, and a favorable attitude toward reduction of AMU and toward SDCT. For the multivariable logistic regression analysis, the first 2 groups were combined and compared with the veterinarians with a favorable attitude. The general attitude of Dutch dairy veterinarians toward reduction of AMU was positive, and most expressed the belief that they can still be a good veterinarian when they prescribe less antimicrobials. Veterinarians indicated they progressively promoted SDCT beginning in 2013. Most veterinarians see the advice they provide to farmers on SDCT as the best possible approach and are convinced that their farmers apply this SDCT approach. The results of the multivariable analyses showed that veterinarians with a favorable attitude mentioned positive aspects of SDCT, such as an increased consciousness of AMU among farmers, improving animal health, reducing antimicrobial resistance, and a chance to add value for the farmer, more often than other veterinarians. The latter group significantly more often indicated negative aspects of SDCT, such as a higher risk of sick cows and feeling pushed to follow the rules. In conclusion, the general attitude of Dutch dairy veterinarians toward reduction of AMU and SDCT was found to be positive. However, given the influence veterinarians potentially have on the attitude of farmers and the variability found in their attitude and behavior, veterinarians need specific attention if regional or national programs are organized trying to change behavior of farmers and encourage prudent AMU and SDCT.



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Effects of fat supplementation to diets high in nonforage fiber on production responses of midlactation dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): C.M. Ylioja, C. Abney-Schulte, R. Stock, B.J. Bradford
The effects of dietary nonforage fiber sources on production responses of lactating dairy cattle have been well described, but interactions with other components of the diet have been less thoroughly explored. We investigated the effects of adding 2 commonly fed fat sources to a ration featuring high levels of nonforage fiber supplied by a corn milling by-product. Midlactation Holstein cows were blocked by parity, stratified by days in milk, and randomly assigned to 1 of 6 pens (12 cows/pen). Pens were randomly assigned to treatment sequences in a 3 × 3 Latin square design, where the treatments consisted of prilled saturated fat (SAT; Energy Booster 100, Milk Specialties Co., Dundee, IL), calcium salts of long-chain fatty acids (UNS; Megalac, Church and Dwight Co. Inc., Princeton, NJ), or no added dietary fat (control), with fat sources included to provide 1.2% added fat (dry matter basis). Treatment periods were 21 d; milk and feed samples were collected and milk yield and feed intake were recorded for the last 4 d of each period. Results were analyzed with mixed models with pen as the experimental unit, and orthogonal contrasts were employed to evaluate the overall effect of added fat and the effect of fat source. Dry matter intake and milk yield tended to increase with added fat. Protein content decreased with fat supplementation, to a greater degree for UNS than for SAT, but protein yield was not affected. Fat content, fat yield, and energy-corrected milk yield were not affected by treatment. Conversion of feed to milk tended to increase for UNS compared with SAT. Fat supplementation to diets high in nonforage fiber had effects that were similar to those reported for more traditional lactation diets, except for the dry matter intake response.



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Characteristics of quinolone-resistant Escherichia coli isolated from bovine mastitis in China

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): Feng Yang, Shidong Zhang, Xiaofei Shang, Ling Wang, Hongsheng Li, Xurong Wang
Escherichia coli is the leading causative agent of bovine mastitis worldwide. Quinolone-resistant E. coli is becoming a potential threat to veterinary and public health. The aim of this study was to investigate the characteristics of quinolone-resistant E. coli isolated from bovine mastitis cases in China. Antimicrobial susceptibility of the isolates against 15 antimicrobial agents was determined by disc diffusion method. Phylogenetic grouping was detected by PCR. Extended-spectrum β-lactamase-producing isolates were determined by double-disc synergy test. In addition, the plasmid-mediated quinolone resistance (PMQR) and β-lactamase-encoding genes, as well as mutations of quinolone resistance-determining regions in GyrA, GyrB, ParC, and ParE, were measured by PCR and DNA sequencing. Overall, 75 (22.9%) out of 328 E. coli isolates were confirmed as ciprofloxacin-resistant from 2,954 mastitic milk samples. Phylogenetic group analysis showed that the majority of these strains belonged to phylogenetic group A (57.3%) and group B1 (24.0%). All the resistant isolates were identified as multidrug resistant, showing high resistance to cephalosporins and non-β-lactams. Forty-nine (65.3%) of the quinolone-resistant isolates were positive for PMQR genes; aac-(6')-Ib-cr was the most common PMQR determinant detected in 33 (44.0%) isolates. Eighteen (24.0%), 4 (5.3%), 3 (4.0%), and 1 (1.3%) of the quinolone-resistant isolates were harboring oqxA/B, qepA4, qnrS, and qnrB2, respectively. Additionally, 55 (73.3%) of the quinolone-resistant E. coli isolates were found to be extended-spectrum β-lactamase producers. The preponderant β-lactamase-encoding gene, blaTEM, was detected in 44 (58.7%) isolates; blaCTX-M, blaCMY, and blaSHV were found in 35 (46.7%), 22 (29.3%), and 2 (2.7%) isolates, respectively. Moreover, the most frequently identified substitutions were S83L/D87N or S83L in GyrA, detected in all of the quinolone-resistant isolates. Meanwhile, 74 (98.7%), 33 (44.0%), and 6 (8.0%) of the isolates were carrying substitutions S80I in ParC, S458A in ParE, and S492N in GyrB, respectively. All 58 (77.3%) isolates with a high level of ciprofloxacin resistance (>32 µg/mL) carried single or double mutations in GyrA combined with single mutation in ParC. To the best of our knowledge, this is the first report on the high occurrence of PMQR determinants and quinolone-determining resistant regions mutations in quinolone-resistant E. coli isolated from bovine mastitis in China.



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Use of a culture-independent on-farm algorithm to guide the use of selective dry-cow antibiotic therapy

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): A.K. Vasquez, D.V. Nydam, C. Foditsch, M. Wieland, R. Lynch, S. Eicker, P.D. Virkler
An algorithm using only computer-based records to guide selective dry-cow therapy was evaluated at a New York State dairy farm via a randomized field trial. DairyComp 305 (Valley Ag Software, Tulare, CA) and Dairy Herd Improvement Association test-day data were used to identify cows as low risk (cows that might not benefit from dry-cow antibiotics) or high risk (cows that will likely benefit). Low-risk cows were those that had all of the following: somatic cell count (SCC) ≤200,000 cells/mL at last test, an average SCC ≤200,000 cells/mL over the last 3 tests, no signs of clinical mastitis at dry-off, and no more than 1 clinical mastitis event in the current lactation. Low-risk cows were randomly assigned to receive intramammary antibiotics and external teat sealant (ABXTS) or external teat sealant only (TS) at dry-off. Using pre-dry-off and postcalving quarter-level culture results, low-risk quarters were assessed for microbiological cure risk and new infection risk. Groups were also assessed for differences in first-test milk yield and linear scores, individual milk weights for the first 30 d, and culling and mastitis events before 30 d in milk. A total of 304 cows and 1,040 quarters in the ABXTS group and 307 cows and 1,058 quarters in the TS group were enrolled. Among cows to be dried, the proportion of cows that met low-risk criteria was 64% (n = 611/953). Of cultures eligible for bacteriological cure analysis (n = 171), 93% of ABXTS cured, whereas 88% of TS cured. Of the non-cures, 95% were contributed by the minor pathogens coagulase-negative staphylococci (n = 19/20). These organisms also accounted for 57.5% of new infections (n = 77/134). We found no statistical differences between treatment groups for new infection risk (TS = 7.3% quarters experiencing new infections; ABXTS = 5.5%), milk production (ABXTS = 40.5 kg; TS = 41.2 kg), linear scores (ABXTS = 2.5; TS = 2.7), culling events (ABXTS, n = 18; TS, n = 15), or clinical mastitis events (ABXTS, n = 9; TS, n = 5). Results suggest that the algorithm used decreased dry-cow antibiotic use by approximately 60% without adversely affecting production or health outcomes.



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Changes in the expression of α-tocopherol-related genes in liver and mammary gland biopsy specimens of peripartum dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): S. Haga, M. Miyaji, M. Nakano, H. Ishizaki, H. Matsuyama, K. Katoh, S.G. Roh
Blood α-tocopherol (α-Toc) concentrations decline gradually throughout the prepartum period, reaching the nadir after calving in dairy cows. The 6 α-Toc–related molecules [α-Toc transfer protein (TTPA); afamin; scavenger receptor class B, Type I; ATP-binding cassette transporter A1; tocopherol-associated protein (SEC14L2); and cytochrome P450 family 4, subfamily F, polypeptide 2 (CYP4F2)] are expressed in liver and other peripheral tissues. These molecules could regulate α-Toc transport, blood concentrations, and metabolism of α-Toc. Therefore, the aim of this study was to evaluate the changes in the expression of α-Toc–related genes in liver and mammary gland tissues of dairy cows around calving, which have remained elusive until now. In experiment (Exp.) 1, 28 multiparous Holstein cows were used (from −5 to 6 wk relative to parturition) to monitor the changes in dietary α-Toc intake, blood concentrations of α-Toc, and lipoproteins; in Exp. 2, 7 peripartum Holstein cows were used (from −4 to 4 wk relative to parturition) for liver tissue biopsy; and in Exp. 3, 10 peripartum Holstein cows were used (from −8 to 6 wk relative to parturition) to carry out the mammary gland tissue biopsy and milk sampling. In Exp. 1, the serum α-Toc concentrations declined gradually with decreasing amount of α-Toc intake and plasma high-density lipoprotein concentrations toward calving time. However, in the early lactation period after calving, serum α-Toc concentrations remained at a lower concentration despite the recovery of α-Toc intake and plasma high-density lipoprotein concentrations. In Exp. 2, just after calving, the TTPA, SEC14L2, afamin, and albumin mRNA expression levels in the liver were temporarily downregulated, and the hepatic mRNA levels of endoplasmic reticulum stress-induced unfolded protein response markers and acute-phase response marker increased at calving. In Exp. 3, the concentrations of α-Toc in colostrum were greater than those in precolostrum (samples were collected at wk −1 relative to parturition) and mature milk. The expression of TTPA, SEC14L2, and CYP4F2 mRNA in bovine mammary gland tissue was detected. However, TTPA and SEC14L2 mRNA expressions showed the opposite trends: the expression levels of TTPA mRNA peaked whereas SEC14L2 mRNA reached a nadir at calving. These results indicate that the expression of α-Toc–related genes involved in specific α-Toc transfer and metabolism in the liver and mammary gland are altered during calving. Moreover, these changes might be associated with the maintenance of lower serum α-Toc concentrations after calving.



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Invited review: Whey proteins as antioxidants and promoters of cellular antioxidant pathways

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): Alberto R. Corrochano, Vitaly Buckin, Phil M. Kelly, Linda Giblin
Oxidative stress contributes to cell injury and aggravates several chronic diseases. Dietary antioxidants help the body to fight against free radicals and, therefore, avoid or reduce oxidative stress. Recently, proteins from milk whey liquid have been described as antioxidants. This review summarizes the evidence that whey products exhibit radical scavenging activity and reducing power. It examines the processing and treatment attempts to increase the antioxidant bioactivity and identifies 1 enzyme, subtilisin, which consistently produces the most potent whey fractions. The review compares whey from different milk sources and puts whey proteins in the context of other known food antioxidants. However, for efficacy, the antioxidant activity of whey proteins must not only survive processing, but also upper gut transit and arrival in the bloodstream, if whey products are to promote antioxidant levels in target organs. Studies reveal that direct cell exposure to whey samples increases intracellular antioxidants such as glutathione. However, the physiological relevance of these in vitro assays is questionable, and evidence is conflicting from dietary intervention trials, with both rats and humans, that whey products can boost cellular antioxidant biomarkers.



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Responses of dairy cows with divergent residual feed intake as calves to metabolic challenges during midlactation and the nonlactating period

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): K. DiGiacomo, E. Norris, F.R. Dunshea, B.J. Hayes, L.C. Marett, W.J. Wales, B.J. Leury
Residual feed intake (RFI) is defined as the difference between the actual and expected feed intake required to support animal maintenance and growth. Thus, a cow with a low RFI can obtain nutrients for maintenance and growth from a reduced amount of feed compared with a cow with a high RFI. Variation in RFI is underpinned by a combination of factors, including genetics, metabolism, thermoregulation and body composition; hypothalamic-pituitary-adrenal (HPA) axis responsiveness is also a possible contributor. Responses to 3 metabolic challenges were measured in lactating and nonlactating dairy cattle. Sixteen Holstein Friesian cows with phenotypic RFI measurements that were obtained during the growth period (188–220 d old) were grouped as either low-calfhood RFI (n = 8) or high-calfhood RFI (n = 8). An ACTH (2 µg/kg of body weight), insulin (0.12 U/kg), and epinephrine (a low dose of 0.1 µg/kg and a high dose of 1.6 µg/kg of epinephrine) challenge were each conducted during both midlactation (122 ± 23.4 d in milk) and the nonlactating period (dry period; approximately 38 d after cessation of milking). Cows were housed in metabolism stalls for the challenges and were fed a diet of alfalfa cubes ad libitum for at least 10 d before the experiment (lactating cows also were offered a total of 6 kg of dry matter/d of crushed wheat grain plus minerals fed as 3 kg of dry matter at each milking) and were fasted for 12 h before the challenges. The efficiency of conversion of feed into milk (the ratio of feed consumed to milk produced over the 7 d before the experiment) during midlactation was better (lower) in low-calfhood RFI cows, although dry matter intake did not differ between RFI groups. Low-calfhood RFI cows exhibited a lower plasma cortisol response to the ACTH challenge than high-calfhood RFI cows, particularly in midlactation (−15%). The low-calfhood RFI cows had a greater plasma insulin-like growth factor-1 response to the insulin challenge and plasma fatty acid response to epinephrine compared with the high-calfhood RFI cows. These data suggest that high-calfhood RFI cows exhibit a more responsive HPA axis. As divergence in RFI measured during growth is retained (although reduced) during lactation, it is possible that energy is used to respond to HPA axis activation at the expense of production in high-calfhood RFI dairy cattle during lactation and contributes to a decrease in overall feed use efficiency.



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Technical note: High-throughput method for antifungal activity screening in a cheese-mimicking model

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): Lucille Garnier, Marcia Leyva Salas, Nicolas Pinon, Norman Wiernasz, Audrey Pawtowski, Emmanuel Coton, Jérôme Mounier, Florence Valence
In this study, we developed a high-throughput antifungal activity screening method using a cheese-mimicking matrix distributed in 24-well plates. This method allowed rapid screening of a large variety of antifungal agent candidates: bacterial fermented ingredients, bacterial isolates, and preservatives. Using the proposed method, we characterized the antifungal activity of 44 lactic acid bacteria (LAB) fermented milk-based ingredients and 23 LAB isolates used as protective cultures against 4 fungal targets (Mucor racemosus, Penicillium commune, Galactomyces geotrichum, and Yarrowia lipolytica). We also used this method to determine the minimum inhibitory concentration of a preservative, natamycin, against 9 fungal targets. The results underlined the strain-dependency of LAB antifungal activity, the strong effect of fermentation substrate on this activity, and the effect of the screening medium on natamycin minimum inhibitory concentration. Our method could achieved a screening rate of 1,600 assays per week and can be implemented to evaluate antifungal activity of microorganisms, fermentation products, or purified compounds compatible with dairy technology.



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Interaction of 5-hydroxy-l-tryptophan and negative dietary cation-anion difference on calcium homeostasis in multiparous peripartum dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): C.J. Slater, E.L. Endres, S.R. Weaver, A.A. Cheng, M.R. Lauber, S.F. Endres, E. Olstad, A. DeBruin, P.M. Crump, E. Block, L.L. Hernandez
Hypocalcemia affects almost 50% of all dairy cows. Our laboratory has previously demonstrated that infusions of the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP) increase circulating calcium concentrations in the Holstein transition cow. It is unknown whether feeding a negative DCAD diet alters the relationship between 5-HTP and hypocalcemia. The main objective of this study was to determine whether feeding a negative dietary cation-anion difference (−DCAD) diet before calving in conjunction with 5-HTP treatment could further diminish the magnitude of hypocalcemia at the time of calving. We used a randomized complete block design with a 2 × 2 factorial arrangement. Thirty-one multiparous Holstein cows were fed either a positive (+13 mEq/100 g) or negative (−13 mEq/100 g) DCAD diet 21 d before parturition and were intravenously infused daily with saline or 5-HTP (1 mg/kg) starting 7 d before the estimated date of parturition. Cows were blocked by parity and were randomly assigned to 1 of 4 treatment groups: positive DCAD plus saline, positive DCAD plus 5-HTP, negative DCAD plus saline, and negative DCAD plus 5-HTP, resulting in n = 8 per group. Total calcium (tCa), ionized calcium (iCa), and feed intake were recorded. The iCa was elevated prepartum in the −DCAD/5-HTP group compared with the other treatment groups as well as on d 0 and 1 postpartum. Although differences in tCa were not significant across the pre- or postpartum periods, tCa was numerically higher on d 0 and significantly higher on d 1 in −DCAD/5-HTP cows compared with all other groups. Prepartum the −DCAD/5-HTP treatment group ate less than the other treatment groups; however, postpartum dry matter intake differences were not significant. These findings demonstrate that feeding a −DCAD diet in conjunction with 5-HTP prepartum can increase postpartum circulating iCa concentrations and therefore diminish the magnitude of hypocalcemia at the time of parturition.



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Intravenous lipid infusion affects dry matter intake, methane yield, and rumen bacteria structure in late-lactating Holstein cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): Ole Lamp, Henry Reyer, Winfried Otten, Gerd Nürnberg, Michael Derno, Klaus Wimmers, Cornelia C. Metges, Björn Kuhla
Increasing the dietary fat content of ruminant diets decreases methane (CH4) production. This effect is caused by the toxic properties of fatty acids on rumen microbial populations, coating of feed particles diminishing the accessibility for microbes, and a reduction in dry matter intake (DMI). The latter effect is caused by postabsorptive long-chain fatty acids eliciting anorexic signaling; however, whether circulating long-chain fatty acids affect rumen CH4 production alike is unknown. To approach this question, 5 rumen-cannulated Holstein cows in late lactation received 2 jugular catheters and were kept in respiration chambers to measure CH4 production and DMI for 48 h. In a crossover design, cows were intravenously infused with a 20% lipid emulsion (LIPO) or 0.9% NaCl (CON). The LIPO cows received 2.1 kg of triglycerides/d [0.152 ± 0.007 g of triglycerides/(kg of BW × h)⁻¹] consisting of 12.1% palmitic acid, 4.2% stearic acid, 31.1% oleic acid, and 52.7% linoleic acid. Blood and rumen fluid samples were taken hourly during the day. Results showed that LIPO compared with CON infusion increased plasma triglyceride as well as free fatty acid and serotonin concentrations but reduced the proportion of de novo synthesized milk fatty acids (sum of C6 to C16). Daily CH4 production and DMI were lower, whereas daily CH4 yield (CH4/DMI) was greater in LIPO than CON cows, although CH4 yield decreased from d 1 to d 2 by 2 to 14% in LIPO-infused cows only. This effect was associated with a higher (acetate + butyrate)/propionate ratio, tending lower propionate concentrations between 24 and 34 h of infusion, reduced relative abundances of genera belonging to Succinivibrio, Ruminococcaceae, and Ruminiclostridium, and greater relative Bacteroidetes genus abundances in the rumen.



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Low colostrum yield in Jersey cattle and potential risk factors

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): K. Gavin, H. Neibergs, A. Hoffman, J.N. Kiser, M.A. Cornmesser, S. Amirpour Haredasht, B. Martínez-López, J.R. Wenz, D.A. Moore
Consumption of an adequate volume of high-quality colostrum is vital to a dairy calf's ability to survive and become a productive herd member. However, some dairy herds have reported a deficiency of colostrum production, which ranges from a low volume to no colostrum produced, by cows during fall and winter. Little information regarding this phenomenon exists. The purpose of this study was to characterize the syndrome and identify potential risk factors for low colostrum yield. A 2,500-cow Jersey dairy farm was enrolled in a prospective cohort study in May 2016, to evaluate possible effects of photoperiod, temperature, and cow factors on colostrum production. Dairy personnel were trained to collect, weigh, and evaluate colostrum quality. Information on parity, previous lactation length, previous 305-d mature equivalent milk production, and dry period length were collected through the farm's dairy management software. Weather and photoperiod data were also collected. Over the year of enrollment, 2,988 eligible cows calved and had colostrum weights recorded and 38% were primiparous (n = 1,143), 25% were in their second lactation (n = 752), and 37% were in their third or greater lactation (n = 1,093). The overall average colostrum yield was 6.6 kg/cow in June 2016, 2.5 kg/cow in December 2016, and 4.8 kg/cow in May 2017. Multiparous cows had a larger decline in colostrum production between June and December (6.6 to 1.3 kg/cow) compared with primiparous animals (6.5 to 4.2 kg/cow). Overall, average colostrum production decreased by 0.17 kg/cow per week during this time, 0.22 kg for multiparous cows and 0.08 kg for primiparous cows. A logistic regression model was constructed for all cows to evaluate effects of cow factors on low colostrum production (<2.7 kg at first milking). Dry period length, calf sex, singleton or twin, age at freshening, month of calving and previous lactation length were significantly associated with the probability of low colostrum yield (<2.7 kg at first milking). A cross-correlation function analysis between the time series for colostrum yield and photoperiod revealed a high correlation at the time of calving and 1 mo prior, particularly for multiparous cows. A pedigree analysis showed that extreme colostrum yield (low vs. high) followed some sire lines. Low colostrum production in this herd could have an economic effect on the dairy and calf health and appears to have a strong seasonal and, potentially, a genetic component.



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Effects of spray-dried plasma protein product on early-lactation dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): C. Lee, A.W. Tebbe, J.M. Campbell, W.P. Weiss
Spray-dried plasma protein (SDP) compared with blood meal (BM) may contain various functional and active components that may benefit animal health. The objective of this experiment was to investigate the effects of feeding SDP or BM on production and blood profile in dairy cows during the transition and early-lactation periods. Seventy-two Holstein cows at 14 d before calving were used in a randomized block design. During the prepartum period, cows were fed a typical late-gestation diet containing BM (100 g/cow per day; 100BM, n = 24) or SDP (100 g/cow per day; 100SDP; n = 48). After calving, cows that were fed BM prepartum were fed a typical lactation diet formulated to provide 100 g/d of BM (100BM). Half the cows that were fed 100SDP prepartum were fed a lactation diet formulated to provide 100 g/d of SDP (100SDP; n = 24), and half were fed a diet formulated to provide 400 g/d of SDP (400SDP; n = 24) on a dry matter basis where SDP replaced BM (100SDP) or BM and soybean products (400SDP). All diets were balanced for crude protein concentration and metabolizable protein supply assuming BM and SDP were equal in rumen-degradable protein and rumen-undegradable protein. All data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) as a randomized block design where contrasts were made for 100BM versus 100SDP for prepartum variables and 100BM versus 100SDP and 100SDP versus 400SDP for postpartum variables. Prepartum supplementation of SDP had no effect on plasma fatty acids and β-hydroxybutyrate (2 d before calving). Plasma fatty acids (255 ± 29 µEq/mL) and β-hydroxybutyrate (675 ± 70 µmol/L) at 8 and 14 d of lactation were not affected by SDP in the diet. Feeding SDP at 100 g/d compared with 100BM increased or tended to increase milk fat, protein, and lactose contents for 16 wk after parturition. Providing SDP at 400 g/d in the diet increased milk yield (42 vs. 39 kg/d), energy-corrected milk (44 vs. 41 kg/d), energy-corrected milk per kilogram of dry matter intake, and yields of milk fat (1.60 vs. 1.48 kg/d), protein (1.21 vs. 1.16 kg/d), and lactose compared with 100SDP. Body weight losses tended to be lower for 100SDP compared with 100BM without a difference between 100SDP and 400SDP. Plasma histidine concentration (d 14 of lactation) was lower for SDP compared with 100BM. In addition, plasma 1-methyl-l-histidine tended to be lower as inclusion rate of SDP increased. In conclusion, SDP at 400 g/d increased milk and milk component yields without an increase in feed intake. Studies evaluating effects of functional and active compounds in SDP on gut microbiome, gut health, and immune functions may be needed to determine mode of action.



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Behavior of Escherichia coli O157:H7 during the manufacture and ripening of Fontina Protected Designation of Origin cheese

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): A. Bellio, D.M. Bianchi, N. Vitale, L. Vernetti, S. Gallina, L. Decastelli
This study was conducted to describe the cheese-making procedure of Fontina Protected Designation of Origin (PDO) cheese and to evaluate the behavior of Escherichia coli O157:H7 during cheese manufacture and ripening. The study was divided into 2 phases: the production of Fontina PDO cheese was monitored at 3 different dairies in the Aosta Valley and an E. coli O157 challenge was conducted at a fourth dairy. The dairies employ different commercial starter cultures for cheese making. The growth of lactic acid bacilli (LAB) and the decrease in pH were slower in the first hours and the LAB concentrations were overall higher in dairy A than in the other 2 dairies. The pH remained substantially unchanged during ripening (range 5.2 to 5.4) in all dairies. Water activity remained constant at around 0.98 until d 21, when it decreased to around 0.97 until d 80 in dairies A and B and 0.95 in dairy E. Whole raw cow milk was used for making Fontina cheese according to the standard procedure. For the experimental production, the milk was inoculated with E. coli O157:H7 at a concentration of approximately 5 log10 cfu/mL and commercial starter cultures were used according to the Fontina PDO regulation. An increase of 2.0 log10 cfu/g in E. coli O157:H7 was observed during the first 9.5 h of cheese making, followed by a decrease at 46 h when pH decreased to 5.4 in all trials. Fresh cheeses were salted and held at 10°C for ripening for 80 d. Water activity was decreased to 0.952 at the end of the ripening stage. The LAB concentrations declined gradually; this trend was more marked for the lactobacilli than either the thermophilic or the mesophilic lactococci. The increase in LAB count and the decrease in pH in the first hours did not seem to affect E. coli O157 growth. Ripening was found to inhibit pathogen survival, however, as seen in the reduction of 3 log10 from the maximum concentration measured during the earlier stages of production.



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Effects of nutrition on the fertility of lactating dairy cattle

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): R.M. Rodney, P. Celi, W. Scott, K. Breinhild, J.E.P. Santos, I.J. Lean
This meta-analysis of 39 experiments containing 118 treatments explored the effects of diet interventions in early lactation on the proportion of dairy cows pregnant to artificial insemination (AI; pregnancy to AI) and on calving to pregnancy interval. It also identified factors that may explain variation in these responses. The objectives were to identify effects of diet on reproduction, rather than differences between specific dietary interventions. The examination of calving to pregnancy interval used the more traditional method of analyzing differences between a treatment and the reference treatment used for comparison within a given experiment. The systematic review identified fewer experiments (n = 39) than had been expected. Four different multivariable models including the random effect of experiment were used to examine the effects of CPM-Dairy (version 3.08) estimated diet and production variables on proportion pregnant to AI. These models examined (1) output of products, (2) balance or duodenal availability of nutrients, (3) intake of nutrients, or (4) percentage of nutrients in the diet. The multivariable models identified positive associations between estimated increased fatty acid intake [incidence rate ratio (IRR) = 1.0003 ± 0.0001g/d; ±standard error], starch intake (IRR = 1.061 ± 0.029 kg/d), metabolizable energy balance (IRR = 1.004 ± 0.002 MJ/d), and duodenal C14:0 (IRR = 1.008 ± 0.004 g/d) availability with the proportion of cows pregnant to AI, whereas rapidly fermentable sugar intake (IRR = 0.813 ± 0.054 kg/d), percentage of sugar in the diet (IRR = 0.960 ± 0.015%), and milk protein yield (IRR 0.922 ± 0.022 g/100 g per day) were associated with a reduced proportion of cows pregnant to AI. There was no multivariable model developed to assess variables associated with calving to pregnancy interval but, univariably, increased metabolizable energy balance was associated with a shorter calving to pregnancy interval whereas increased milk production was associated with longer time to pregnancy. Increased intake of some AA, particularly threonine and lysine, were associated with a longer calving to pregnancy interval. It is clear nutritional management around calving can influence reproductive success. The importance of dietary fats and increased energy and protein balances in early lactation for improved fertility outcomes is supported and suggests that starch and sugars may have different effects on the proportion of cows that are pregnant to AI. This work also highlighted a need for further focused field studies exploring the roles of specific fatty acids, AA, phosphorus, and carbohydrates on reproduction.



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Symposium review: Amino acid uptake by the mammary glands: Where does the control lie?

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): John P. Cant, Julie J.M. Kim, Scott R.L. Cieslar, John Doelman
Milk protein yield responses to changes in the profile of essential amino acids absorbed by the gastrointestinal tract or circulating in blood plasma do not follow the classic limiting amino acid response, in part because of an ability of the mammary glands to modify their blood flow rate and net clearance of amino acids out of plasma. The hypothesis that mammary blood flow is locally regulated to maintain ATP balance accounts for observed changes in flow due to postruminal glucose, insulin, and essential amino acid (EAA) infusions. An additional hypothesis that net mammary uptakes of metabolites from blood are affected by perturbations in their respective arterial concentrations and the rate of mammary blood flow also appears to hold for the energy metabolites glucose, acetate, β-hydroxybutyrate, and fatty acids. However, net EAA uptakes by the mammary glands are poorly predicted by models considering arterial concentrations and blood flow rates only. Evidence points to intramammary protein synthesis and secretion as the determinant of net EAA uptake. The intracellular signaling network anchored by the mechanistic target of rapamycin complex 1 stands as an excellent candidate to explain nutritional effects on milk protein synthesis because it integrates information on physiological and nutritional state to affect protein synthesis and cell metabolism, growth, proliferation, and differentiation in many cell types. In mammary cells in vitro and in vivo, the mechanistic target of rapamycin complex 1, integrated stress response, and glycogen synthase kinase-3 networks that contribute to regulation of initiation of mRNA translation are responsive to acute changes in nutrient supply and EAA profile. However, after several days of postruminal infusion of balanced and imbalanced EAA profiles, these signaling networks do not appear to continue to account for changes in milk protein yields. Gene expression evidence suggests that regulation of components of the unfolded protein response that control biogenesis of the endoplasmic reticulum and differentiation of a secretory phenotype may contribute to effects of nutrition on milk protein yield. Connections between early signaling events and their long-term consequences should be sought.



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Milk mid-infrared spectral data as a tool to predict feed intake in lactating Norwegian Red dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): S.E. Wallén, E. Prestløkken, T.H.E. Meuwissen, S. McParland, D.P. Berry
Mid-infrared (MIR) spectroscopy of milk was used to predict dry matter intake (DMI) and net energy intake (NEI) in 160 lactating Norwegian Red dairy cows. A total of 857 observations were used in leave-one-out cross-validation and external validation to develop and validate prediction equations using 5 different models. Predictions were performed using (multiple) linear regression, partial least squares (PLS) regression, or best linear unbiased prediction (BLUP) methods. Linear regression was implemented using just milk yield (MY) or fat, protein, and lactose concentration in milk (Mcont) or using MY together with body weight (BW) as predictors of intake. The PLS and BLUP methods were implemented using just the MIR spectral information or using the MIR together with Mcont, MY, BW, or NEI from concentrate (NEIconc). When using BLUP, the MIR spectral wavelengths were always treated as random effects, whereas Mcont, MY, BW, and NEIconc were considered to be fixed effects. Accuracy of prediction (R) was defined as the correlation between the predicted and observed feed intake test-day records. When using the linear regression method, the greatest R of predicting DMI (0.54) and NEI (0.60) in the external validation was achieved when the model included both MY and BW. When using PLS, the greatest R of predicting DMI (0.54) and NEI (0.65) in the external validation data set was achieved when using both BW and MY as predictors in combination with the MIR spectra. When using BLUP, the greatest R of predicting DMI (0.54) in the external validation was when using MY together with the MIR spectra. The greatest R of predicting NEI (0.65) in the external validation using BLUP was achieved when the model included both BW and MY in combination with the MIR spectra or when the model included both NEIconc and MY in combination with MIR spectra. However, although the linear regression coefficients of actual on predicted values for DMI and NEI were not different from unity when using PLS, they were less than unity for some of the models developed using BLUP. This study shows that MIR spectral data can be used to predict NEI as a measure of feed intake in Norwegian Red dairy cattle and that the accuracy is augmented if additional, often available data are also included in the prediction model.



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Effect of human chorionic gonadotrophin administration 2 days after insemination on progesterone concentration and pregnancy per artificial insemination in lactating dairy cows

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): J.M. Sánchez, F. Randi, C. Passaro, D.J. Mathew, S.T. Butler, P. Lonergan
The aim of this study was to examine the effect of a single administration of human chorionic gonadotrophin (hCG) during the establishment of the corpus luteum (CL) on progesterone (P4) concentration and pregnancy per artificial insemination (P/AI) in lactating dairy cows. Postpartum spring-calving lactating dairy cows (n = 800; mean ± SD days in milk and parity were 78.5 ± 16.7 and 2.3 ± 0.8, respectively) on 3 farms were enrolled on the study. All cows underwent the same fixed-time AI (FTAI) protocol involving a 7-d progesterone-releasing intravaginal device with gonadotrophin-releasing hormone (GnRH) administration at device insertion, prostaglandin at device removal followed by GnRH 56 h later, and AI 16 h after the second GnRH injection. Cows were blocked on days postpartum, body condition score, and parity and randomly assigned to receive either 3,000 IU of hCG 2 d after FTAI or no further treatment (control). Blood samples were collected on d 7 and 14 postestrus by coccygeal venipuncture on a subset of 204 cows to measure serum P4 concentration, and pregnancy was diagnosed by ultrasonography approximately 30 and 70 d after FTAI. Administration of hCG caused an increase in circulating P4 concentrations compared with the control treatment on d 7 (+22.2%) and d 14 (+25.7%). The P/AI at 30 d after FTAI was affected by treatment, farm, body condition score, and calving to service interval. Overall, administration of hCG decreased P/AI (46.3% vs. 55.1% for the control). Among cows that did not become pregnant following AI, a greater proportion of control cows exhibited a short repeat interval (≤17 d) compared with cows treated with hCG (8.6% vs. 2.8%, respectively). In addition, the percentages of cows pregnant at d 21 (59.6% vs. 52.0%) and d 42 (78.3% vs. 71.9%) were greater in control than in hCG-treated cows. The overall incidence of embryo loss was 10.7% and was not affected by treatment. There was a tendency for an interaction between treatment and CL status at synchronization protocol initiation for both P4 concentration and P/AI. In conclusion, administration of hCG 2 d after FTAI increased circulating P4 concentrations. Unexpectedly, cows treated with hCG had lower fertility; however, this negative effect on fertility was manifested primarily in cows lacking a CL at the onset of the synchronization protocol.



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The effect of using cow genomic information on accuracy and bias of genomic breeding values in a simulated Holstein dairy cattle population

Publication date: Available online 28 March 2018
Source:Journal of Dairy Science
Author(s): E. Dehnavi, S. Ansari Mahyari, F.S. Schenkel, M. Sargolzaei
Using cow data in the training population is attractive as a way to mitigate bias due to highly selected training bulls and to implement genomic selection for countries with no or limited proven bull data. However, one potential issue with cow data is a bias due to the preferential treatment. The objectives of this study were to (1) investigate the effect of including cow genotype and phenotype data into the training population on accuracy and bias of genomic predictions and (2) assess the effect of preferential treatment for different proportions of elite cows. First, a 4-pathway Holstein dairy cattle population was simulated for 2 traits with low (0.05) and moderate (0.3) heritability. Then different numbers of cows (0, 2,500, 5,000, 10,000, 15,000, or 20,000) were randomly selected and added to the training group composed of different numbers of top bulls (0, 2,500, 5,000, 10,000, or 15,000). Reliability levels of de-regressed estimated breeding values for training cows and bulls were 30 and 75% for traits with low heritability and were 60 and 90% for traits with moderate heritability, respectively. Preferential treatment was simulated by introducing upward bias equal to 35% of phenotypic variance to 5, 10, and 20% of elite bull dams in each scenario. Two different validation data sets were considered: (1) all animals in the last generation of both elite and commercial tiers (n = 42,000) and (2) only animals in the last generation of the elite tier (n = 12,000). Adding cow data into the training population led to an increase in accuracy (r) and decrease in bias of genomic predictions in all considered scenarios without preferential treatment. The gain in r was higher for the low heritable trait (from 0.004 to 0.166 r points) compared with the moderate heritable trait (from 0.004 to 0.116 r points). The gain in accuracy in scenarios with a lower number of training bulls was relatively higher (from 0.093 to 0.166 r points) than with a higher number of training bulls (from 0.004 to 0.09 r points). In this study, as expected, the bull-only reference population resulted in higher accuracy compared with the cow-only reference population of the same size. However, the cow reference population might be an option for countries with a small-scale progeny testing scheme or for minor breeds in large counties, and for traits measured only on a small fraction of the population. The inclusion of preferential treatment to 5 to 20% of the elite cows led to an adverse effect on both accuracy and bias of predictions. When preferential treatment was present, random selection of cows did not reduce the effect of preferential treatment.



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Potential application of pre-treated municipal solid waste incineration fly ash as cement supplement

Abstract

Pre-treatment process carried out on raw municipal solid waste incineration (MSWI) fly ash (FA) sample that did not comply initially with the USEPA method 1311 toxicity characteristic leaching procedure (TCLP) regulatory limits of 2011 reduced its chloride and heavy metal content appreciably, thereby making it compliant with the aforementioned regulatory requirement. More than 98% of each heavy metal was successfully removed. The process was excellent in removing cadmium (Cd) (99.99%) and very good at removing the rest. About 99.96% of Cu was eliminated, 99.96% of cobalt (Co), 99.95% of Zn, 98.61% of Cr, and 98.12% of nickel (Ni). Also, the leachate resulting from these pre-treatment steps met the China (GB 16889-2008) and USEPA method 1311 regulatory standards for safe discharge. The density and compressive strength of all the samples prepared increased as the FA content decreased. The compressive strength of all the samples passed the 1989 USEPA-recommended value of 0.34 MPa (50 psi), thereby making them suitable for industrial application. The sample that attained the highest compressive strength (2.08 MPa) after 28 days of curing incorporated 55% fly ash (FACS55), while the one with the least compressive strength (0.65 MPa) after the same period was made from only fly ash (FACS100). Moreover, the concentration of heavy metals in all the samples generally decreased with the FA content. Chromium was not detected in all the samples, thereby making this an excellent method for its immobilization. From the leachability test results, all the samples prepared met the USEPA method 1311 TCLP regulatory limits.

https://ift.tt/2E0BzKV

Toxicity evaluation of process water from hydrothermal carbonization of sugarcane industry by-products

Abstract

Hydrothermal carbonization (HTC) is a thermochemical process carried out in an aqueous medium. It is capable of converting biomass into a solid, carbon-rich material (hydrochar), and producing a liquid phase (process water) which contains the unreactive feedstock and/or chemical intermediates from the carbonization reaction. The aim of this study was to evaluate the characteristics of process water generated by HTC from vinasse and sugarcane bagasse produced by sugarcane industry and to evaluate its toxicity to both marine (using Artemia salina as a model organism) and the terrestrial environment (through seed germination studies of maize, lettuce, and tomato). The experiments showed that concentrated process water completely inhibited germination of maize, lettuce, and tomato seeds. On the other hand, diluted process water was able to stimulate seedlings of maize and tomato and enhance root and shoot growth. For Artemia, the LC₅₀ indicated that the process water is practically non-toxic; however, morphological changes, especially damages to the digestive tube and antennas of Artemia, were observed for the concentration of 1000 mg C L⁻¹.

https://ift.tt/2GUzcfQ

Decomposition dynamic of two aquatic macrophytes Trapa bispinosa Roxb. and Nelumbo nucifera detritus

Abstract

In freshwater ecosystems, aquatic macrophytes play significant roles in nutrient cycling. One problem in this process is nutrient loss in the tissues of untimely harvested plants. In this study, we used two aquatic species, Nelumbo nucifera and Trapa bispinosa Roxb., to investigate the decomposition dynamics and nutrient release from detritus. Litter bags containing 10 g of stems (plus petioles) and leaves for each species detritus were incubated in the pond from November 2016 to May 2017. Nine times litterbags were retrieved on days 6, 14, 25, 45, 65, 90, 125, 145, and 165 after the decomposition experiment for the monitoring of biomass loss and nutrient release. The results suggested that the dry masses of N. nucifera and T. bispinosa decomposed by 49.35–69.40 and 82.65–91.65%, respectively. The order of decomposition rate constants (k) is as follows: leaves of T. bispinosa (0.0122 day⁻¹) > stems (plus petioles) of T. bispinosa (0.0090 day⁻¹) > leaves of N. nucifera (0.0060 day⁻¹) > stems (plus petioles) of N. nucifera (0.0030 day⁻¹). Additionally, the orders of time for 50% dry mass decay, time for 95% dry mass decay, and turnover rate are as follows: leaves < stems (plus petioles) and T. bispinosa < N. nucifera, respectively. This result indicated that the dry mass loss, k values, and other parameters related to k values are significantly different in species- and tissue-specific. The C, N, and P concentration and the C/N, C/P, and N/P ratios presented the irregular temporal changes trends during the whole decay period. In addition, nutrient accumulation index (AI) was significantly changed depending on the dry mass remaining and C, N, and P concentration in detritus at different decomposition times. The nutrient AIs were 36.72, 8.08, 6.35, and 2.56% for N; 31.25, 9.85, 4.00, and 1.63% for P; 25.15, 16.96, 7.36, and 6.16% for C in the stems (plus petioles) of N. nucifera, leaves of N. nucifera, stems (plus petioles) of T. bispinosa, and leaves of T. bispinosa, respectively, at the day 165. These results indicated that 63.28–97.44% of N, 68.75–98.37% of P, and 74.85–93.84% of C were released from the plant detritus to the water at the day 165 of the decomposition period. The initial detritus chemistry, particularly the P-related parameters (P concentration and C/P and N/P ratios), strongly affected dry mass loss, decomposition rates, and nutrient released from detritus into water. Two-way ANOVA results also confirm that the effects on the species were significant for decomposition dynamics (dry mass loss), nutrient release (nutrient concentration, their ratios, and nutrient AI) (P < 0.01), and expected N concentration (P > 0.05). In addition, the decomposition time had also significant effects on the detritus decomposition dynamic and nutrient release. However, the contributors of species and decomposition time on detritus decomposition were significantly different on the basis of their F values of two-way ANOVA results. This study can provide scientific bases for the aquatic plant scientific management in freshwater ecosystems of the East region of China.

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MCE – Special issue on updates on steroid signalling in breast cancer

Publication date: 5 May 2018
Source:Molecular and Cellular Endocrinology, Volume 466
Author(s): Keely McNamara, Hironobu Sasano




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The interplay of endocrine therapy, steroid pathways and therapeutic resistance: Importance of androgen in breast carcinoma

Publication date: 5 May 2018
Source:Molecular and Cellular Endocrinology, Volume 466
Author(s): Kiyoshi Takagi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified. In breast carcinoma tissues, not only ER but androgen receptor (AR) is frequently expressed, suggesting pivotal roles of androgens in the progress of breast carcinomas. Growing interest on androgen action as possible therapeutic target has been taken, but androgen action seems quite complicated in breast carcinomas and inconsistent findings has been also proposed. In this review, we will summarize recent studies regarding intratumoral androgen production and its regulation as well as distinct subset of breast carcinomas characterized by activated AR signaling and recent clinical trial targeting AR in the patients with either ER-positive and ER-negative breast carcinomas.



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Editorial Board

Publication date: 5 May 2018
Source:Molecular and Cellular Endocrinology, Volume 466





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The significance of cholesterol and its metabolite, 27-hydroxycholesterol in breast cancer

Publication date: 5 May 2018
Source:Molecular and Cellular Endocrinology, Volume 466
Author(s): Erik R. Nelson
Although significant advances in the treatment of breast cancer have been made, in particular in the use of endocrine therapy, de novo and aquired resistance to therapy, and metastatic recurrence continue to be major clinical problems. Given the high prevalence of breast cancer, new life-style or chemotherapeutic approaches are required. In this regard, cholesterol has emerged as a risk factor for the onset of breast cancer, and elevated cholesterol is associated with a poor prognosis. While treatment with cholesterol lowering medication is not associated with breast cancer risk, it does appear to be protective against recurrence. Importantly, the cholesterol axis represents a potential target for both life-style and pharmacological intervention. This review will outline the clinical and preclinical data supporting a role for cholesterol in breast cancer pathophysiology. Specific focus is given to 27-hydroxycholesterol (27-OHC; (3β,25R)-Cholest-5-ene-3,26-diol)), a primary metabolite of cholesterol that has recently been defined as an endogenous Selective Estrogen Receptor Modulator. Future perspectives and directions are discussed.



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Mass spectrometry-based metabolic signatures of sex steroids in breast cancer

Publication date: 5 May 2018
Source:Molecular and Cellular Endocrinology, Volume 466
Author(s): Man Ho Choi
Owing to controversy over the effects of steroids on breast cancer pathophysiology, comprehensive quantification of steroid hormones has been extensively considered in both clinical practice and biomarker discovery studies. In contrast to the traditional immunoaffinity-based assays, which show cross-reactivity and have poor validity at low levels of sex steroids, mass spectrometry is becoming a promising tool for measuring steroid levels in complex biological specimens. The Endocrine Society has announced and continuously updated on technical advances to apply high-quality breakthroughs in the clinical sciences. To avoid incorrect estimation of the steroids of interest, however, further emphasis should be made on the efficient separation by chromatography, such as gas and liquid chromatography, prior to mass spectrometric (MS) detection. Recent advances in MS-based analysis of sex steroids associated with breast cancer enable accurate quantification of circulating as well as localized steroids from frozen tissue slices, allowing these assays to be more powerful in clinical practice.



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MiR-451a attenuates free fatty acids–mediated hepatocyte steatosis by targeting the thyroid hormone responsive spot 14 gene

Publication date: Available online 29 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Ni Zeng, Rong Huang, Nan Li, Hongmei Jiang, Ruobi Li, Fei Wang, Wen Chen, Min Xia, Qing Wang
The thyroid hormone responsive spot 14 (THRSP) gene is a de novo lipogenesis-related gene that plays a significant role in the initiation and development of nonalcoholic fatty liver disease (NAFLD). Several previous studies had shown that endogenous and environmental factors could regulate the expression of THRSP. The role of microRNAs (miRNAs), however, in controlling THRSP expression has not been investigated. In this study, we first constructed the hepatic steatosis cell model by using a mixture of free fatty acids (FFAs; oleate/palmitate, 2:1 ratio) to treat and demonstrate the promotive role of THRSP in lipid accumulation in hepatic cells. By analyzing the photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) database and performing a luciferase reporter assay, we confirmed that microRNA-451a specifically binds to mouse and human THRSP 3′UTR and inhibits its activity. Overexpression of miR-451a efficiently reduced THRSP mRNA and protein expression as well as triglyceride (TG) accumulation in cultured hepatic cells (AML12 and HepG2). Moreover, overexpression of miR-451a significantly decreases TG accumulation in the livers of mice injected with an miR-451a agomir. All these results demonstrated that miR-451 might participate in the FFA-induced hepatic steatosis by regulating the expression of the THRSP gene which represents a new potential target for NAFLD therapy.

Graphical abstract

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Heating boosts graphene’s conductivity

Publication date: Available online 28 March 2018
Source:Materials Today
Author(s): Cordelia Sealy




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Solar energy harnessed by new ‘double-glazing’ approach

Publication date: Available online 28 March 2018
Source:Materials Today
Author(s): Laurie Donaldson




https://ift.tt/2pSKj0K

ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer

Publication date: Available online 28 March 2018
Source:Radiotherapy and Oncology
Author(s): Ursula Nestle, Dirk De Ruysscher, Umberto Ricardi, Xavier Geets, Jose Belderbos, Christoph Pöttgen, Rafal Dziadiuszko, Stephanie Peeters, Yolande Lievens, Coen Hurkmans, Ben Slotman, Sara Ramella, Corinne Faivre-Finn, Fiona McDonald, Farkhad Manapov, Paul Martin Putora, Cécile LePéchoux, Paul Van Houtte
Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies.



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Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN)

Publication date: Available online 28 March 2018
Source:Radiotherapy and Oncology
Author(s): Alessandra Bolsi, Marta Peroni, Dante Amelio, Alexandru Dasu, Markus Stock, Iuliana Toma-Dasu, Petra Witt Nyström, Aswin Hoffmann
Background and purposeImage guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres.Material and methodsIn 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT.ResultsAll centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods.ConclusionsInsight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines.



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Susceptibility-weighted magnetic resonance imaging of cerebrovascular sequelae after radiotherapy for pediatric brain tumors

Publication date: Available online 28 March 2018
Source:Radiotherapy and Oncology
Author(s): Marie A. Neu, Yasemin Tanyildizi, Arthur Wingerter, Nicole Henninger, Khalifa El Malki, Francesca Alt, Barbara Doerr, Heinz Schmidberger, Marcus Stockinger, Wolfgang Wagner, Stefanie Keweloh, Marc A. Brockmann, Alexandra Russo, Joerg Faber
Background and purposeDue to sensitive neuroimaging techniques, cerebrovascular complications such as cerebral microbleeds (CMB) and cerebral cavernous malformations (CCM) are increasingly recognized as considerable late effects after treatment for pediatric brain tumor. The aim of this study was to analyze CMB in a cohort of patients after cranial irradiation therapy for medulloblastoma or other pediatric brain tumors using susceptibility-weighted magnetic resonance imaging (SWI).Materials and methodsForty former pediatric brain tumor patients were enrolled in this prospective cross-sectional study and examined by cranial MRI including SWI sequences. Cerebral microbleeds, clinical symptoms and disability were evaluated.ResultsThirty-six (90%) of the examined individuals (mean follow-up age 22.2 y; mean follow-up time 13.5 y) were affected by CMB. Longer follow-up time and higher craniospinal irradiation doses correlated with higher total lesion count (p < 0.01). Thirteen patients (32.5%) presented with clinical symptoms. Individuals with CMB were more severely disabled than patients without CMB (p < 0.05).ConclusionsCerebrovascular sequelae occur frequently after treatment for pediatric brain tumor. In this study, a remarkable part of pediatric brain tumor patients presents with CMB. As a sign of vascular damage, they can cause clinical symptoms and may correspond to neurocognitive decline. Further studies are needed to standardize MRI protocols and to improve quality of long-term follow-up.



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Is accurate contouring of salivary and swallowing structures necessary to spare them in head and neck VMAT plans?

Publication date: Available online 28 March 2018
Source:Radiotherapy and Oncology
Author(s): Alexander R. Delaney, Max Dahele, Ben J. Slotman, Wilko F.A.R. Verbakel
Background and purposeCurrent standards for organ-at-risk (OAR) contouring encourage anatomical accuracy which can be resource intensive. Certain OARs may be suitable for alternative delineation strategies. We investigated whether simplified salivary and swallowing structure contouring can still lead to good OAR sparing in automated head and neck cancer (HNC) plans.Materials and methodsFor 15 HNC patients, knowledge-based plans (KBPs) using RapidPlan™ were created using: (1) standard clinical contours for all OARs (benchmark-plans), (2) automated knowledge-based contours for the salivary glands, with standard contours for the remaining OARs (SS-plans) and (3) simplified contours (SC-plans) consisting of quick-to-draw tubular structures to account for the oral cavity, salivary glands and swallowing muscles. Individual clinical OAR contours in a RapidPlan™ model were combined to create composite salivary/swallowing structures. These were matched to tube-contours to create SC-plans. All plans were compared based on dose to anatomically accurate clinical OAR contours.ResultsSalivary gland delineation in SS-plans required on average 2 min, compared with 7 min for manual delineation of all tubular-contours. Automated atlas-based contours overlapped with, on average, 71% of clinical salivary gland contours while tube-contours overlapped with 95%/75%/93% of salivary gland/oral cavity/swallowing structure contours. On average, SC-plans were comparable to benchmark-plans and SS-plans, with average differences in composite salivary and swallowing structure dose ≤2 Gy and <1 Gy respectively.ConclusionsSimplified-contours could be created quickly and resulted in clinically acceptable HNC VMAT plans. They can be combined with automated planning to facilitate the implementation of advanced radiotherapy, even when resources are limited.



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Global distribution and evolvement of urbanization and PM2.5 (1998–2015)

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Dongyang Yang, Chao Ye, Xiaomin Wang, Debin Lu, Jianhua Xu, Haiqing Yang
PM2.5 concentrations increased and have been one of the major social issues along with rapid urbanization in many regions of the world in recent decades. The development of urbanization differed among regions, PM2.5 pollution also presented discrepant distribution across the world. Thus, this paper aimed to grasp the profile of global distribution of urbanization and PM2.5 and their evolutionary relationships. Based on global data for the proportion of the urban population and PM2.5 concentrations in 1998–2015, this paper investigated the spatial distribution, temporal variation, and evolutionary relationships of global urbanization and PM2.5. The results showed PM2.5 presented an increasing trend along with urbanization during the study period, but there was a variety of evolutionary relationships in different countries and regions. Most countries in East Asia, Southeast Asia, South Asia, and some African countries developed with the rapid increase in both urbanization and PM2.5. Under the impact of other socioeconomic factors, such as industry and economic growth, the development of urbanization increased PM2.5 concentrations in most Asian countries and some African countries, but decreased PM2.5 concentrations in most European and American countries. The findings of this study revealed the spatial distributions of global urbanization and PM2.5 pollution and provided an interpretation on the evolution of urbanization-PM2.5 relationships, which can contribute to urbanization policies making aimed at successful PM2.5 pollution control and abatement.



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Coordination of Cell Polarity, Mechanics and Fate in Tissue Self-organization

Publication date: Available online 28 March 2018
Source:Trends in Cell Biology
Author(s): Esther Jeong Yoon Kim, Ekaterina Korotkevich, Takashi Hiiragi
Self-organization guides robust, spatiotemporally ordered formation of complex tissues and ultimately whole organisms. While products of gene expression serve as building blocks of living matter, how these interact to give rise to tissues of distinct patterns and function remains a central question in biology. Tissue self-organization relies on dynamic interactions between constituents spanning a range of spatiotemporal scales with tuneable chemical and mechanical parameters. This review highlights recent studies dissecting mechanisms of these interactions. We propose that feedback interactions between cell polarity, mechanics, and fate are a key principle underlying tissue self-organization. We also provide a glimpse into how such processes can be studied in future endeavors.



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Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan‐Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

AbstractLessons Learned. A phase I study of the pan‐class I phosphoinositide 3‐kinase inhibitor pilaralisib (in capsule formulation) in advanced solid tumors established the maximum tolerated dose as 600 mg once daily.The current study investigated pilaralisib in tablet formulation.Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity.Based on pharmacokinetic data, the recommended phase II dose of pilaralisib tablets was established as 400 mg once daily.Background.A phase I trial of pilaralisib, an oral pan‐class I phosphoinositide 3‐kinase (PI3K) inhibitor, established the maximum tolerated dose (MTD) of the capsule formulation in patients with advanced solid tumors as 600 mg once daily. This phase I study investigated pilaralisib in tablet formulation.Materials and Methods.Patients with advanced solid tumors received pilaralisib tablets (100–600 mg once daily). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics, and efficacy.Results.Twenty‐two patients were enrolled. No dose‐limiting toxicities (DLTs) were reported. The most common treatment‐related adverse events were diarrhea (40.9%), fatigue (40.9%), decreased appetite (22.7%), and hyperglycemia (22.7%). Pilaralisib plasma exposure did not appear to increase dose‐proportionally. Steady‐state exposure was higher with pilaralisib tablet formulation at 400 mg than with pilaralisib capsule formulation at 400 or 600 mg (mean area under the curve [AUC0–24] 2,820,000 ng × h/mL vs. 2,653,000 and 1,930,000 ng × h/mL, respectively). Of 18 evaluable patients, 2 (11.1%) had a partial response (PR).Conclusion.Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity. MTD was not determined. The recommended phase II dose for pilaralisib tablets, based on PK data, was 400 mg once daily.

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Administration of the Tablet Formulation of Olaparib in Patients with Ovarian Cancer: Practical Guidance and Expectations

AbstractOlaparib is a poly(ADP‐ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic BRCA1/2 mutations who have received three or more prior lines of chemotherapy for maintenance treatment of recurrent OC that is in response to platinum‐based chemotherapy regardless of BRCA mutation status and for human epidermal growth receptor factor 2‐negative metastatic breast cancer with deleterious or suspected deleterious germline BRCA mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Because olaparib is poorly soluble and requires advanced drug delivery techniques to ensure bioavailability, the originally approved 400 mg dose is taken as eight 50 mg capsules twice daily. An alternative melt‐extrusion tablet formulation was developed to improve the pharmacokinetic and pharmacodynamic profile of olaparib and reduce the pill burden for patients. The recommended tablet dose is 300 mg twice daily (two 150 mg tablets). Phase III studies with the tablet formulation are ongoing for multiple tumor types. Two studies conducted with the olaparib tablet formulation have reported results: one in platinum‐sensitive, BRCA‐mutated recurrent OC (SOLO‐2) and one that included patients with germline BRCA‐mutated metastatic breast cancer (OlympiAD). The tablet is the approved formulation based on the SOLO‐2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC. Prior to implementing any changes in therapy, health care providers should engage their patients in discussion to support an informed transition between the formulations.Implications for Practice.Olaparib has recently been approved for maintenance treatment of recurrent ovarian cancer (OC) that is in response to platinum‐based chemotherapy. The originally approved capsule formulation was dosed as 400 mg twice daily (eight 50 mg capsules). The recommended olaparib tablet dose is 300 mg twice daily (two 150 mg tablets). The tablet is the new approved formulation based on the SOLO‐2 trial results. Because the capsule and tablet formulations have different bioavailability, physicians must strictly adhere to the dosing instructions provided in the prescribing information. The tablet offers greater convenience for most patients, especially when using olaparib for maintenance therapy. This review discusses the differences between the two formulations, dose determination, and guidance for use of olaparib tablets by patients with OC.

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Toward universal influenza virus vaccines: from natural infection to vaccination strategy

Publication date: August 2018
Source:Current Opinion in Immunology, Volume 53
Author(s): Chen Zhao, Jianqing Xu
Conceptually, a universal influenza vaccine should elicit broadly protective antibody responses targeting highly conserved epitope(s) shared by various virus strains. Strategically directing antibody immunity to the conserved hemagglutinin stalk has recently emerged as a promising approach that is substantiated by the identification of naturally occurring, stalk-reactive human antibodies capable of conferring broad protection against influenza virus challenge in animal models. Despite all the advancements, future realization of this strategy still faces many challenges, particularly whether it is able to induce enough of cross-reactive antibody response to protect against pandemic viruses. In this respect, recent in-depth dissections of human immune responses to H7N9 virus and vaccination provide much-needed new insights.



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Issue Information ‐ TOC

Australian Dental Journal, Volume 63, Issue S1, Page S3-S3, March 2018.


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Guest Editorial Contemporary Oral & Maxillofacial Surgery

Australian Dental Journal, Volume 63, Issue S1, Page S1-S2, March 2018.


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Craniofacial disorders

Australian Dental Journal, Volume 63, Issue S1, Page S58-S68, March 2018.


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Paediatric oral & maxillofacial surgery

Australian Dental Journal, Volume 63, Issue S1, Page S69-S78, March 2018.


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Issue Information ‐ JEB

Australian Dental Journal, Volume 63, Issue S1, March 2018.


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Management of temporomandibular joint disorders: A surgeon's perspective

Australian Dental Journal, Volume 63, Issue S1, Page S79-S90, March 2018.


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Extractions to reconstruction: The Development of Oral & Maxillofacial Surgery in Australian and New Zealand

Australian Dental Journal, Volume 63, Issue S1, Page S4-S10, March 2018.


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Oral Cancer

Australian Dental Journal, Volume 63, Issue S1, Page S91-S99, March 2018.


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The contemporary management of third molars

Australian Dental Journal, Volume 63, Issue S1, Page S19-S26, March 2018.


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Implant based rehabilitation options for the atrophic edentulous jaw

Australian Dental Journal, Volume 63, Issue S1, Page S100-S107, March 2018.


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Current and evolving trends in the management of facial fractures

Australian Dental Journal, Volume 63, Issue S1, Page S35-S47, March 2018.


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Reconstruction of major defects of the jaws

Australian Dental Journal, Volume 63, Issue S1, Page S108-S113, March 2018.


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The teaching of oral & maxillofacial surgery to dental students in Australia & New Zealand

Australian Dental Journal, Volume 63, Issue S1, Page S114-S117, March 2018.


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Highly sensitive detection of hepatitis C virus DNA by using a one-donor-four-acceptors FRET probe

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Ping Zeng, Peng Hou, Chun Ju Jing, Cheng Zhi Huang
Sensitive detection of Hepatitis C virus (HCV) DNA is critical to treat and prevent the propagation of hepatitis C diseases. Herein a FRET probe of One-Donor-Multi-Acceptors (D–mA) assembly is designed through the formation of triple-helix DNA structure, which can greatly reduce the background of FRET system so as to greatly increase the detection sensitivity of hepatitis C virus DNA with the limit of detection (3σ) being 24.57 nmol/L, making the detection of clinic samples successful and showing that the newly developed FRET probe of D–mA assembly could be applied for the early diagnosis and treatment of hepatitis C disease.

Graphical abstract

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One-pot synthesis of the stable CdZnTeS quantum dots for the rapid and sensitive detection of copper-activated enzyme

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Guobin Mao, Chen Liu, Mingyuan Du, Yuwei Zhang, Xinghu Ji, Zhike He
Galactose oxidase is a copper-activated enzyme and have a vital role in metabolism of galactose. Much of the work is focused on determining the amount of galactose in the blood rather than measuring the amount of galactose oxidase to urge the galactosemia patients to restrict milk intake. Here, a simple and effective method was developed for Cu²⁺ and copper-activated enzyme detection based on homogenous alloyed CdZnTeS quantum dots (QDs). Meso− 2,3-dimercaptosuccinic acid (DMSA) was used as the reducing agent for preparing QDs and the highest quantum yield of CdZnTeS QDs was 69.4%. In addition, the as-prepared CdZnTeS QDs show superior fluorescence properties, such as good photo-/chemical stability. The DMSA was the surface ligand of the QDs, containing abundant -SH and -COOH, thus the surface ligands have a high affinity with Cu²⁺. Therefore, this developed probe can be applied for Cu²⁺ and galactose oxidase detection and shows a good sensitivity in the buffer. Then, this probe was successfully used for Cu²⁺ and galactose oxidase detection in real samples with the satisfactory results. The proposed fluorescence quenching strategy gives a new and simple insight for enzyme assay without the enzyme-catalyzed reaction.

Graphical abstract

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N-doped carbon nanotubes-reinforced hollow fiber solid-phase microextraction coupled with high performance liquid chromatography for the determination of phytohormones in tomatoes

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Xiao-Fei Han, Juan Chen, Yan-Ping Shi
A N-doped carbon nanotubes-reinforced hollow fiber solid-phase microextraction (N-doped CNTs-HF-SPME) method was developed for determination of two naphthalene-derived phytohormones, 1-naphthalene acetic acid (NAA) and 2-naphthoxyacetic acid (2-NOA), at trace levels in tomatoes. N-doped CNTs were dispersed in ultrapure water with the assistance of surfactant, and then immobilized into the pores of hollow fiber by capillary forces and sonification. The resultant N-doped CNTs-HF was wetted with 1-octanol, subsequently immersed into the tomato samples to extract the target analytes under a magnetic stirring, and then desorbed with methanol by sonication prior to chromatographic analysis. Compared with CNTs, the surface hydrophilicity of N-doped CNTs was improved owing to the doping of nitrogen atoms, and a uniform dispersion was formed, thus greatly simplifying the preparation process and reducing waste of materials. In addition, N-doped CNTs-HF exhibits a more effective extraction performance for NAA and 2-NOA on account of the introduction of Lewis-basic nitrogen. It is worth to mention that owing to the clean-up function of HF, there are not any complicated sample pretreatment procedures prior to the microextraction. To achieve the highest extraction efficiency, important microextraction parameters including the length and the concentration level of N-doped CNTs in surfactant solution, extraction time, desorption conditions such as the type and volume of solvents, pH value, stirring rate and volume of the donor phase were thoroughly investigated and optimized. Under the optimal conditions, the method showed 165- and 123-fold enrichment factors of NAA and 2-NOA, good inter-fiber repeatability and batch-to-batch reproducibility, good linearity with correlation coefficients higher than 0.9990, low limits of detection and quantification (at ng g⁻¹ levels), and satisfactory recoveries in the range of 83.10–108.32% at three spiked levels. The proposed method taking advantages of both excellent adsorption performance of N-doped CNTs and the clean-up function of HF, was a simple, green, efficient and cost-effective enrichment procedure for the determination of trace NAA and 2-NOA in tomatoes.

Graphical abstract

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Aligner-mediated cleavage-triggered exponential amplification for sensitive detection of nucleic acids

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Wanghua Wu, Hongliang Fan, Xiang Lian, Jianguang Zhou, Tao Zhang
Exponential amplification reaction (EXPAR), as a simple and high sensitive method, holds great promise in nucleic acids detection. One major challenge in EXPAR is the generation of trigger DNA with a definite 3′-end, which now relies on fingerprinting technology. However, the requirement of different endonucleases for varying target sequences and two head-to-head recognition sites in double stranded DNA, as well as the confinement of trigger DNA's 3′-end to be near/within the recognition site, usually subject EXPAR to compromised universality and/or repeated matching of reaction conditions. Herein, we report a simple and universal method for high sensitive detection of nucleic acids, termed aligner-mediated cleavage-triggered exponential amplification (AMCEA). The aligner-mediated cleavage (AMC) needs only one nicking endonuclease and can make a break at any site of choice in a programmable way. Thus, the 3′-end of target DNA can be easily redefined as required, a key step for initiating the amplification reaction. This capability endows the proposed AMCEA with excellent universality and simplicity. Moreover, it is sensitive and specific, with a detection limit at amol level, a broad dynamic range of 5～6 orders of magnitude and the ability to distinguish single nucleotide mutation. Experiments performed with human serum indicate that AMCEA is compatible with the complex biological sample, and thus has the potentials for practical applications.

Graphical abstract

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Ultrasensitive detection of thiophenol based on a water-soluble pyrenyl probe

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Zhiyi Yao, Wenqi Ge, Mingwei Guo, Keren Xiao, Yadong Qiao, Zhong Cao, Hai-Chen Wu
We report a simple pyrene-based fluorescent probe, sodium 8-(2,4-dinitrophenoxy)pyrene-1,3,6-trisulfonate (HPTS-DNP), for the ultrasensitive and visual detection of thiophenol in 100% aqueous media. The sensing mechanism of this method is based on nucleophilic aromatic substitution on HPTS-DNP caused by thiophenol to afford a highly fluorescent product, 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS). The extremely low fluorescence background of HPTS-DNP and high quantum yield of HPTS ensure the superior sensing performance toward thiophenol, including rapid responses, off-on detection mode and excellent sensitivity. The detection limit is as low as 0.49 nmol L⁻¹ according to the measurements with a spectrofluorimeter. This probe also features good selectivity (response ratio of thiophenol to interferents >30), precision (2.93%) and accuracy (102%). This approach could be applied for monitoring the thiophenol concentrations in environmental water samples. HPTS-DNP also showed good cell permeation capacity and low cellular cytotoxicity, indicating further application in bioimaging studies.

Graphical abstract

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