Usefulness of mid-infrared spectroscopy as a tool to estimate body condition score change from milk samples in intensively-fed dairy cows.

Directly measuring individual cow energy balance is not trivial. Other traits, like body condition score (BCS) and BCS change (ΔBCS) can, however, be used as an indicator of cow energy status. Body condition score is a metric used world-wide to estimate cow body reserves and the estimation of ΔBCS was, until now, conditional on the availability of multiple BCS assessments. The aim of the present study was to estimate ΔBCS from milk mid-infrared (MIR) spectra and days in milk (DIM) in intensively-fed dairy cows using statistical prediction methods. Daily BCS was interpolated from cubic splines fitted through the BCS records and daily ΔBCS was calculated from these splines. Body condition score change records were merged with milk MIR spectra recorded on the same week. The data set comprised 37,077 ΔBCS phenotypes across 9,403 lactations from 6,988 cows in 151 herds based in Quebec (Canada). Partial least squares regression (PLSR) and a neural network (NN) were then used to estimate ΔBCS from 1) MIR spectra only, 2) DIM only, or 3) MIR spectra and DIM together. ΔBCS data in both the first 120 DIM and 305 DIM of lactation were used to develop the estimates. Daily ΔBCS had a standard deviation of 4.40*10-3 BCS units in the 120-d data set and of 3.63*10-3 BCS units in the 305-d data set. 4-fold cross-validation was used to calibrate and test the prediction equations. External validation was also conducted using more recent years of data. Irrespective of whether based on the first 120 or 305 DIM, or when MIR spectra only, DIM only or MIR spectra and DIM were jointly used as prediction variables, NN produced the lowest root mean square error (RMSE) of cross-validation (1.81*10-3 BCS units and 1.51*10-3 BCS units, respectively, using the 120-d and 305-d data set). Relative to predictions for the entire 305 DIM, the RMSE of cross-validation was 15.4% and 1.5% lower in the first 120 DIM when using PLSR and NN, respectively. Predictions from DIM only were more accurate than those using just MIR spectra data but, irrespective of the data set and of the prediction model used, the combining DIM information with MIR spectral data as prediction variables reduced the RMSE compared with inclusion of DIM alone, albeit the benefit was small (the RMSE from cross-validation was reduced up to 5.5% when DIM and spectral data were jointly used as model features instead of DIM only). However, when predicting extreme ΔBCS records, the MIR spectral data was more informative than DIM. Model performance when predicting ΔBCS records in future years was similar to that from cross-validation demonstrating the ability of MIR spectra of milk and DIM combined to estimate ΔBCS, particularly in early lactation. This can be used to routinely generate estimates of ΔBCS to aid in day-to-day individual cow management

The Uses of Chiral Anomaly for Determination of the Number of Colors

The $N_c$-dependence of the vertices $PPP\gamma$, where $P$ is a pseudoscalar meson and $N_c$ is the number of colors, is analyzed with regard for the $N_c$-dependence of the quark charges. It is shown that the best processes for the determination of $N_c$ are the reactions $K\gamma \to K\pi$ and $\pi^pm\gamma\to\pi^\pm\eta$ as well as the decay \eta\ra\pi^+\pi^-\gamma. The measurement of the cross section \sigma(\pi^-\gamma\ra\pi^-\eta) at the VES facility at the IHEP agrees with the value $N_c=3$.Comment: 7 pages, 1 figure; accepted to Phys. Atom. Nucl., references adde

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3–p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis

Lipocalin-2 is a sensitive and specific marker of bacterial iInfection in children

Abstract Introduction Bacterial infection is the leading cause of death in children globally. Clinical algorithms to identify children who are likely to benefit from antimicrobial treatment remain suboptimal. Biomarkers that accurately identify serious bacterial infection (SBI) could improve diagnosis and clinical management. Lipocalin 2 (LCN2) and neutrophil collagenase (MMP-8) are neutrophil-derived biomarkers associated with bacterial infection. Methods We evaluated LCN2 and MMP-8 as candidate biomarkers in 40 healthy controls and 151 febrile children categorised confirmed SBI, probable SBI, or viral infection. The diagnostic performance of LCN2 and MMP-8 to predict SBI was estimated by the area under the receiver operating characteristic curve (AUROC) and compared to the performance of C-reactive protein (CRP). Results Plasma LCN2 and MMP-8 concentration were predictive of SBI. The AUROC (95% CI) for LCN2, MMP8 and CRP to predict SBI was 0.88 (0.82-0.94); 0.80 (0.72-0.87) and 0.89 (0.84-0.94), respectively. The diagnostic performance of LCN2 in combination with CRP was significantly superior to either marker alone: AUROC 0.92 (95% CI: 0.88-0.96). Conclusion LCN2 is a sensitive and specific predictor of SBI in children which could be used to improve clinical management and antimicrobial stewardship. LCN2 should be further evaluated in prospective clinical studies

Labour self-sufficiency on family dairy farms in Ireland: a case study approach considering labour requirement, input and management

The efficient use of labour input is essential to the success of farms; however, many countries are experiencing a decreasing family workforce on-farm as a result of perceived labour intensive work and poor work–life balance. Four farms identified from two labour time-use studies were selected as case studies to investigate management of the family dairy farm in terms of herd size, while also meeting the labour requirements and maintaining a satisfactory work–life balance. A mixed methods approach was used; quantitative analysis described the labour profile and characteristics of the farms, while the qualitative interviews provided insights into strategies to achieve labour efficiency. The results demonstrate that a family farm with a herd size of ∼120 cows with appropriate facilities and streamlined practices can operate effectively with a total labour input of 2,986 h/yr. The labour contributed by the farmer and the farm family represented 77.5% of the total annual labour requirement. Contractors or hired employees contributed the remaining labour input, depending on individual circumstances. The annual average working day length for the farmer (excluding breaks) was 7.8 h/d. The analysed narratives of the farmers demonstrated their view that a seasonal, pasture-based spring calving system of production is a key influence in achieving relatively high labour efficiency on-farm, if it is ensured that the peak workload in spring is managed effectively. The study highlights that the overall labour demand can be reduced on Irish family farms through the management of facilities and practices. The farmer and family members can then decide on the degree of self-sufficiency with regard to labour, that is, what proportion of that labour they wish to contribute based on their lifestyle choices, cost and availability of contractors and hired workers

Effects of the Pre-K Program of Kalamazoo County Ready 4s on Kindergarten Entry Test Scores: Estimates Based on Data from the Fall of 2011 and the Fall of 2012

This paper uses a regression discontinuity model to examine the effects on kindergarten entrance assessments of the Kalamazoo County Ready 4s (KC Ready 4s) program, a half-day pre-K program for four-year-olds in Kalamazoo County, Michigan. The results are based on test scores and other characteristics of up to 220 children participating in KC Ready 4s, with data coming from both 2011–2012 and 2012–2013 participants in the program. The estimates find consistently statistically significant effects of this pre-K program on improving entering kindergartners’ math test scores. Some estimates also suggest marginally statistically significant effects of KC Ready 4s on vocabulary test scores. No statistically significant effects are found on letter-word identification test scores, due in part to the small available sample size, but some of the point estimates are large. The program does not appear to have large or statistically significant effects in improving children’s behavioral assessments. The overall average effects of KC Ready 4s on the three academic test scores are large, at an effect size of at least 0.52. This is toward the high end of effects found in previous studies of short-term effects of pre-K programs. These estimates also are consistent with program benefits exceeding program costs

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD

Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome

peer-reviewedBackground Currently, a number of bioinformatics methods are available to generate appropriate lists of genes from a microarray experiment. While these lists represent an accurate primary analysis of the data, fewer options exist to contextualise those lists. The development and validation of such methods is crucial to the wider application of microarray technology in the clinical setting. Two key challenges in clinical bioinformatics involve appropriate statistical modelling of dynamic transcriptomic changes, and extraction of clinically relevant meaning from very large datasets. Results Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p < 0.05), followed by muscle (601 genes) and adipose (16 genes). Results from modified GSEA showed that the high-CLA beef diet affected diverse biological processes across the three tissues, and that the majority of pathway changes reached significance only with the bi-directional test. Combining the liver tissue microarray results with plasma marker data revealed 110 CLA-sensitive genes showing strong canonical correlation with one or more plasma markers of metabolic health, and 9 significantly overrepresented pathways among this set; each of these pathways was also significantly changed by the high-CLA diet. Closer inspection of two of these pathways - selenoamino acid metabolism and steroid biosynthesis - illustrated clear diet-sensitive changes in constituent genes, as well as strong correlations between gene expression and plasma markers of metabolic syndrome independent of the dietary effect. Conclusion Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest correlation with the clinical markers of interest. In this case, we have identified selenoamino acid metabolism and steroid biosynthesis as key pathways mediating the observed relationship between metabolic health and high-CLA beef. These results indicate that this type of analysis has the potential to generate novel transcriptome-based biomarkers of disease.Department of Agriculture and Food, Ireland - Food Institutional Research Measure (project no. 5254); IRCSET postgraduate scholarship scheme (MJM); Science Foundation Ireland Principal Investigator Programme (HMR) Programme

Transcriptomic Profiling in Childhood H1N1/09 Influenza Reveals Reduced Expression of Protein Synthesis Genes

We compared the blood RNA transcriptome of children hospitalized with influenza A H1N1/09, respiratory syncytial virus (RSV) or bacterial infection, and healthy controls. Compared to controls, H1N1/09 patients showed increased expression of inflammatory pathway genes and reduced expression of adaptive immune pathway genes. This was validated on an independent cohort. The most significant function distinguishing H1N1/09 patients from controls was protein synthesis, with reduced gene expression. Reduced expression of protein synthesis genes also characterized the H1N1/09 expression profile compared to children with RSV and bacterial infection, suggesting that this is a key component of the pathophysiological response in children hospitalized with H1N1/09 infection

Development and Evaluation of an Enzyme-Linked Immunosorbent Assay for Use in the Detection of Bovine Tuberculosis in Cattle

As a consequence of continued spillover of Mycobacterium bovis into cattle from wildlife reservoirs and increased globalization of cattle trade with associated transmission risks, new approaches such as vaccination and novel testing algorithms are seriously being considered by regulatory agencies for the control of bovine tuberculosis. Serologic tests offer opportunities for identification of M. bovis-infected animals not afforded by current diagnostic techniques. The present study describes assay development and field assessment of a new commercial enzyme-linked immunosorbent assay (ELISA) that detects antibody to M. bovis antigens MPB83 and MPB70 in infected cattle. Pertinent findings include the following: specific antibody responses were detected at 90 to 100 days after experimental M. bovis challenge, minimal cross-reactive responses were elicited by infection/sensitization with nontuberculous Mycobacterium spp., and the apparent sensitivity and specificity of the ELISA with naturally infected cattle were 63% and 98%, respectively, with sensitivity improv- ing as disease severity increased. The ELISA also detected infected animals missed by the routine tuberculin skin test, and antibody was detectable in bulk tank milk samples from M. bovis-infected dairy herds. A high-throughput ELISA could be adapted as a movement, border, or slaughter surveillance test, as well as a supplemental test to tuberculin skin testing