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This paper is based on a keynote address delivered at the diamond jubilee congress of the Royal College of Nursing at Harrogate, England, on 5 April 1976. After discussing the functional and dysfunctional aspects of aggression in society, the author reviews the recent literature, citing British and American studies conducted in psychiatric, mental handicap and general hospitals. The effects of environment and disease processes are identified and the implications of violence in patients are discussed, particularly the implications for trained nurses and nursing students. The author contends that it is violence rather than aggression that needs to be eradicated from society and pleads for more research-based knowledge about violence, arguing that 'knowledge must come before treatment'. [ABSTRACT FROM AUTHOR]

This study investigated the genetics of bovine tuberculosis (bTB) infectivity in Holstein-Friesian dairy cows using British national data. The analyses included cows with recorded sires from herds affected by bTB outbreaks between 2000 and 2022. Animals were considered bTB-positive if they reacted positively to the skin test and/or had positive post-mortem findings. We introduced the "index case approach," based on the assumption that once the initial positively tested animals (index cases) are detected in a herd, subsequent infections (secondary cases) in the early stages of the breakdown are likely to be attributed to these animals. Genetic analysis of the number of secondary cases (NSC) associated with a given index case was used to establish evidence of genetic variability in bTB infectivity of cattle, and derive Estimated Breeding Values (EBVs) for infectivity for the sires of the index cases. Data were analyzed by employing Markov Chain Monte Carlo techniques to fit Generalized Linear Mixed Models with either Poisson, Zero-Inflated Poisson (ZIP), Hurdle Poisson, or Geometric distributions. All 4 models demonstrated presence of genetic variance in cattle infectivity, with the strongest evidence provided by the ZIP and Hurdle Poisson models. The Hurdle Poisson model offered the most accurate and least biased predictions. Sire infectivity EBVs from the Poisson, ZIP, and Geometric models showed strong concordance, with pairwise correlations of 0.90 or higher. In contrast, correlations between EBVs from the Hurdle Poisson model and the other models ranged from 0.36 to 0.39. The association of the sire infectivity EBVs with the average observed NSC per sire and the proportion of infectious index case daughters per sire was generally moderate with correlations between 44 and 47% and 65-69%, respectively. Agreement among models for identifying the genetically most infectious sires was also reasonable, with 151 out of 285 sires appearing in the top 10% across models, and 122 (42.8%) also aligning with the top 10% based on observed average NSC. Results provide novel evidence for exploitable genetic variance in bTB infectivity allowing the derivation of meaningful EBVs. Based on the estimated posterior mean genetic variances obtained, reduction in infectivity by one genetic standard deviation would result in a 32% - 44% decrease in the expected NSC per index case. Further research is warranted to refine the phenotypic definition of infectivity and assess correlation with other dairy traits., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Accurately identifying pregnancy status is imperative for a profitable dairy enterprise. Mid-infrared (MIR) spectroscopy is routinely used to determine fat and protein concentrations in milk samples. Mid-infrared spectra have successfully been used to predict other economically important traits, including fatty acid content, mineral content, body energy status, lactoferrin, feed intake, and methane emissions. Machine learning has been used in a variety of fields to find patterns in vast quantities of data. This study aims to use deep learning, a sub-branch of machine learning, to establish pregnancy status from routinely collected milk MIR spectral data. Milk spectral data were obtained from National Milk Records (Chippenham, UK), who collect large volumes of data continuously on a monthly basis. Two approaches were followed: using genetic algorithms for feature selection and network design (model 1), and transfer learning with a pretrained DenseNet model (model 2). Feature selection in model 1 showed that the number of wave points in MIR data could be reduced from 1,060 to 196 wave points. The trained model converged after 162 epochs with validation accuracy and loss of 0.89 and 0.18, respectively. Although the accuracy was sufficiently high, the loss (in terms of predicting only 2 labels) was considered too high and suggested that the model would not be robust enough to apply to industry. Model 2 was trained in 2 stages of 100 epochs each with spectral data converted to gray-scale images and resulted in accuracy and loss of 0.97 and 0.08, respectively. Inspection on inference data showed prediction sensitivity of 0.89, specificity of 0.86, and prediction accuracy of 0.88. Results indicate that milk MIR data contains features relating to pregnancy status and the underlying metabolic changes in dairy cows, and such features can be identified by means of deep learning. Prediction equations from trained models can be used to alert farmers of nonviable pregnancies as well as to verify conception dates., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Genetic parameters were estimated for cold carcase weight (CCW), carcase conformation (CON), carcase fat class (FAT), age at slaughter (AGE) and average daily carcase gain (ADCG) in 14 common UK breeds of cattle. These included crossbred animals but purebred datasets were also analysed for the most populous sire-breeds. Heritability estimates for beef breeds that were significant ranged from 0.24 to 0.44, 0.12 to 0.35, 0.12 to 0.36, 0.15 to 0.38 and 0.26 to 0.43 for CCW, CON, FAT, AGE and ADCG, respectively. For Holstein-Friesian, a dairy breed, heritability estimates were consistently lower than most beef breeds with estimates of 0.12, 0.13, 0.13, 0.06 and 0.15 for CCW, CON, FAT, AGE and ADCG, respectively. In all breed groups, genetic correlations were positive between CCW, CON and ADCG. In general, genetic correlations were moderate between CCW and CON (0.13 to 0.77), moderate to strong between CCW and ADCG (0.57 to 0.98) and weak or moderate between CON and ADCG (0.12 to 0.82). Genetic correlations for FAT with CCW (- 0.20 to - 0.42) and CON (- 0.16 to - 0.52) tended to be negative in the beef breed but were positive in the dairy breed, although not significant between CCW and FAT. For most beef breeds genetic correlations between AGE and carcase traits were not significant with the exceptions of AGE and CCW for Simmental (- 0.15) and Salers (- 0.24), AGE and CON for Limousin (0.15) and Simmental (0.14) and AGE and FAT from three sire-breeds (- 0.17 to - 0.35). However, the correlation between AGE and ADCG was negative and moderate to strong in magnitude (- 0.23 to - 0.67) in all beef breeds as expected since faster-growing animals reach slaughter age earlier. For Holstein-Friesian, all genetic correlations with AGE were negative and moderate to strong. Genetic correlations indicate that selection for increased carcase weight should simultaneously increase growth rate and improve conformation in all breeds and reduce carcase fatness in the majority of beef breeds. The results indicate that there is genetic variation in all five traits suitable for undertaking genetic improvement of carcase traits and age at slaughter; however, there are apparent breed differences. The use of abattoir-derived phenotypes for undertaking genetic improvement is an example where the supply chain can work together to share information to enable the cattle industry to move forward., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

We measured end-tidal CO levels in 50 jaundiced newborns readmitted for phototherapy at age 54-244 hours. The median end-tidal CO level was 1.55 ppm, suggesting that hemolysis is not the primary contributor to the hyperbilirubinemia in many readmitted newborns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bovine tuberculosis (bTB) is a zoonotic disease in cattle that is transmissible to humans, distributed worldwide, and considered endemic throughout much of England and Wales. Mid-infrared (MIR) analysis of milk is used routinely to predict fat and protein concentration, and is also a robust predictor of several other economically important traits including individual fatty acids and body energy. This study predicted bTB status of UK dairy cows using their MIR spectral profiles collected as part of routine milk recording. Bovine tuberculosis data were collected as part of the national bTB testing program for Scotland, England, and Wales; these data provided information from over 40,500 bTB herd breakdowns. Corresponding individual cow life-history data were also available and provided information on births, movements, and deaths of all cows in the study. Data relating to single intradermal comparative cervical tuberculin (SICCT) skin-test results, culture, slaughter status, and presence of lesions were combined to create a binary bTB phenotype labeled 0 to represent nonresponders (i.e., healthy cows) and 1 to represent responders (i.e., bTB-affected cows). Contemporaneous individual milk MIR spectral data were collected as part of monthly routine milk recording and matched to bTB status of individual animals on the single intradermal comparative cervical tuberculin test date (±15 d). Deep learning, a sub-branch of machine learning, was used to train artificial neural networks and develop a prediction pipeline for subsequent use in national herds as part of routine milk recording. Spectra were first converted to 53 × 20-pixel PNG images, then used to train a deep convolutional neural network. Deep convolutional neural networks resulted in a bTB prediction accuracy (i.e., the number of correct predictions divided by the total number of predictions) of 71% after training for 278 epochs. This was accompanied by both a low validation loss (0.71) and moderate sensitivity and specificity (0.79 and 0.65, respectively). To balance data in each class, additional training data were synthesized using the synthetic minority over sampling technique. Accuracy was further increased to 95% (after 295 epochs), with corresponding validation loss minimized (0.26), when synthesized data were included during training of the network. Sensitivity and specificity also saw a 1.22- and 1.45-fold increase to 0.96 and 0.94, respectively, when synthesized data were included during training. We believe this study to be the first of its kind to predict bTB status from milk MIR spectral data. We also believe it to be the first study to use milk MIR spectral data to predict a disease phenotype, and posit that the automated prediction of bTB status at routine milk recording could provide farmers with a robust tool that enables them to make early management decisions on potential reactor cows, and thus help slow the spread of bTB., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: Conflicting data exist with regard to the effect of needle gauge on outcomes of computed tomography (CT)-guided lung nodule biopsies. The purpose of this study was to compare the complication and diagnostic adequacy rates between 2 needle sizes: 18 G and 20 G in CT-guided lung nodule biopsies., Materials and Methods: This retrospective cohort study examined CT-guided lung biopsies performed between March 2014 and August 2016 with a total of 550 patients between the ages of 30 and 94. Biopsies were performed using an 18-G or a 20-G needle. Procedure-associated pneumothorax and other complication rates were compared between the 2 groups. Univariate and multiple logistic regression analyses were performed., Results: There was no significant difference in pneumothorax rate between 18 G (n=125) versus 20 G (n=425) (rates: 25.6% vs. 28.7%; P=0.50; odds ratio [OR]=0.86; 95% confidence interval [CI]=0.54-1.35), chest tube insertion rate (4.8% vs. 5.6%; P=0.71; OR=0.84; 95% CI=0.34-2.11), or diagnostic adequacy (95% vs. 93%; P=0.36; OR=1.51; 95% CI=0.61-3.72). Multiple logistic regression analysis demonstrated emphysema along the biopsy path (OR=3.12; 95% CI=1.63-5.98) and nodule distance from the pleural surface ≥4 cm (OR=1.85; 95% CI=1.05-3.28) to be independent risk factors for pneumothorax., Conclusion: No statistically significant difference in pneumothorax rate or diagnostic adequacy was found between 18-G versus 20-G core biopsy needles. Independent risk factors for pneumothorax include emphysema along the biopsy path and nodule distance from the pleural surface.

The balance of body energy within and across lactations can have health and fertility consequences for the dairy cow. This study aimed to create a large calibration data set of dairy cow body energy traits across the cow's productive life, with concurrent milk mid-infrared (MIR) spectral data, to generate a prediction tool for use in commercial dairy herds. Detailed phenotypic data from 1,101 Holstein Friesian cows from the Langhill research herd (SRUC, Scotland) were used to generate energy balance (EB) and effective energy intake (EI), both in megajoules per day. Pretreatment of spectral data involved standardization to account for drift over time and machine. Body energy estimates were aligned with their spectral data to generate a prediction of these traits based on milk MIR spectroscopy. After data edits, partial least squares analysis generated prediction equations with a coefficient of determination from split sample 10-fold cross validation of 0.77 and 0.75 for EB and EI, respectively. These prediction equations were applied to national milk MIR spectra on over 11 million animal test dates (January 2013 to December 2016) from 4,453 farms. The predictions generated from these were subject to phenotypic analyses with a fixed regression model highlighting differences between the main dairy breeds in terms of energy traits. Genetic analyses generated heritability estimates for EB and EI ranging from 0.12 to 0.17 and 0.13 to 0.15, respectively. This study shows that MIR-based predictions from routinely collected national data can be used to generate predictions of dairy cow energy turnover profiles for both animal management and genetic improvement of such difficult and expensive-to-record traits., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Health and survival are key goals for selective breeding in farm animals. Progress, however, is often limited by the low heritability of these animal fitness traits in addition to measurement difficulties. In this respect, relevant early-life biomarkers may be useful for breeding purposes. Telomere length (TL), measured in leukocytes, is a good candidate biomarker since TL has been associated with health, ageing, and stress in humans and other species. However, telomere studies are very limited in farm animals. Here, we examined the genetic background, genomic architecture, and factors affecting bovine TL measurements in early life, and the association of the latter with animal fitness traits expressed later in life associated with survival, longevity, health, and reproduction. We studied two TL measurements, one at birth (TLB) and another during the first lactation (TLFL) of a cow. We performed a genome-wide association study of dairy cattle TL, the first in a non-human species, and found that TLB and TLFL are complex, polygenic, moderately heritable, and highly correlated traits. However, genomic associations with distinct chromosomal regions were identified for the two traits suggesting that their genomic architecture is not identical. This is reflected in changes in TL throughout an individual's life. TLB had a significant association with survival, length of productive life and future health status of the animal, and could be potentially used as an early-life biomarker for disease predisposition and longevity in dairy cattle., (Copyright © 2019 Ilska-Warner, Psifidi, Seeker, Wilbourn, Underwood, Fairlie, Whitelaw, Nussey, Coffey and Banos.)

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of autosomal dominant Parkinson's disease (PD) and sporadic PD (sPD). The clinical presentation of LRRK2 PD is similar to sPD, and except for genetic testing, no biochemical or imaging markers can differentiate LRRK2 PD from sPD. Discovery of such biomarkers could indicate neuropathological mechanisms that are unique to or increased in LRRK2 PD. This review discusses findings in 17 LRRK2 - related CSF studies found on PubMed. Most of these studies compared analyte concentrations between four diagnostic groups: LRRK2 PD patients, sPD patients, asymptomatic control subjects carrying PD-associated LRRK2 mutations (LRRK2 CTL), and healthy control subjects lacking LRRK2 mutations (CTL). Analytes examined in these studies included Aβ1-42, tau, α-synuclein, oxidative stress markers, autophagy-related proteins, pteridines, neurotransmitter metabolites, exosomal LRRK2 protein, RNA species, inflammatory cytokines, mitochondrial DNA (mtDNA), and intermediary metabolites. FINDINGS: Pteridines, α-synuclein, mtDNA, 5-hydroxyindolacetic acid, β-D-glucose, lamp2, interleukin-8, and vascular endothelial growth factor were suggested to differentiate LRRK2 PD from sPD patients; 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO), 2-hydroxybutyrate, mtDNA, lamp2, and neopterin may differentiate between LRRK2 CTL and LRRK2 PD subjects; and soluble oligomeric α-synuclein, 8-OHdG, and 8-ISO might differentiate LRRK2 CTL from CTL subjects. CONCLUSIONS: The low numbers of investigations of each analyte, small sample sizes, and methodological differences limit conclusions that can be drawn from these studies. Further investigations are indicated to determine the validity of the analytes identified in these studies as possible biomarkers for LRRK2 PD patients and/or LRRK2 CTL subjects.

Previous work has highlighted that immune-associated (IA) traits measurable in blood are associated with health, productivity, and reproduction in dairy cows. The aim of the present study was to determine relationships between IA traits measured in blood serum and those simultaneously measured in milk as well as their association with disease phenotypes. All animals were Holstein-Friesian cows from the Langhill research herd (n = 546) housed at the SRUC Dairy Research Centre in Scotland. Milk and serum samples were collected on 20 separate occasions between July 2010 and March 2015 and analyzed by ELISA for haptoglobin (Hp), tumor necrosis factor-α (TNF-α), and natural antibodies binding keyhole limpet hemocyanin (NAb KLH ) and lipopolysaccharide (NAb LPS ). Data were analyzed using mixed linear models that included pedigree information. Analyses revealed positive phenotypic correlations between milk and serum NAb (0.59 ≤ r ≤ 0.77), Hp (r = 0.37), and TNF-α (r = 0.12). Milk and serum NAb were also found to have a strong genetic correlation (0.81 ≤ r ≤ 0.94) and were genetically correlated with cow lameness (0.66 and 0.79 for milk NAb KLH and serum NAb LPS , respectively). Clinical mastitis was found to be phenotypically correlated with both milk and serum Hp (0.09 ≤ r ≤ 0.23). Serum Hp was also strongly genetically correlated with other cellular IA traits such as percent NKp46 + (a natural killer cell marker; 0.35) and percent peripheral blood mononuclear cells (PBMC; -0.90). Similarly, genetic correlations were found to exist between serum TNF-α and percent NKp46 + (0.22), percent PBMC (0.41), and percent lymphocytes (0.47). Excluding serum Hp, all milk and serum IA traits were repeatable, ranging from 0.11 (milk Hp) to 0.43 (serum NAb LPS ). Between-animal variation was highest in milk and serum NAb (0.34-0.43) and significant estimates of heritability were also observed in milk and serum NAb (0.17-0.37). Our findings show that certain IA traits, such as NAb KLH and NAb LPS , found in milk and serum are strongly correlated and highlight the potential of using routinely collected milk samples as a less invasive and cost-effective source of informative data for predictive modeling of animal IA traits., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Copy number variants (CNVs) are a form of genomic variation that changes the structure of the genome through deletion or duplication of stretches of DNA. The objective of the present study was to characterize CNVs in a large multibreed population of beef and dairy bulls. The CNVs were called on the autosomes of 5,551 cattle from 22 different beef and dairy breeds, using 2 freely available software suites, QuantiSNP and PennCNV. All CNVs were classified into either deletions or duplications. The median concordance between PennCNV and QuantiSNP, per animal, was 18.5% for deletions and 0% for duplications. The low concordance rate between PennCNV and QuantiSNP indicated that neither algorithm, by itself, could identify all CNVs in the population. In total, PennCNV and QuantiSNP collectively identified 747,129 deletions and 432,523 duplications; 80.2% of all duplications and 69.1% of all deletions were present only once in the population. Only 0.154% of all CNVs identified were present in more than 50 animals in the population. The distribution of the percentage of the autosomes that were composed of deletions, per animal, was positively skewed, as was the distribution for the percentage of the autosomes that were composed of duplications, per animal. The first quartile, median, and third quartile of the distribution of the percentage of the autosomes that were composed of deletions were 0.019%, 0.037%, and 0.201%, respectively. The first quartile, median, and third quartile of the distribution of the percentage of the autosomes that were composed of duplications were 0.013%, 0.028%, and 0.076%, respectively. The distributions of the number of deletions and duplications per animal were both positively skewed. The interquartile range for the number of deletions per animal in the population was between 16 and 117, whereas for duplications it was between 8 and 23. Per animal, there tended to be twice as many deletions as duplications. The distribution of the length of deletions was positively skewed, as was the distribution of the length of duplications. The interquartile range for the length of deletions in the population was between 25 and 101 kb, and for duplications the interquartile range was between 46 and 235 kb. Per animal, duplications tended to be twice as long as deletions. This study provides a description of the characteristics and distribution of CNVs in a large multibreed population of beef and dairy cattle.

Average telomere length (TL) in blood cells has been shown to decline with age in a range of vertebrate species, and there is evidence that TL is a heritable trait associated with late-life health and mortality in humans. In non-human mammals, few studies to date have examined lifelong telomere dynamics and no study has estimated the heritability of TL, despite these being important steps towards assessing the potential of TL as a biomarker of productive lifespan and health in livestock species. Here we measured relative leukocyte TL (RLTL) in 1,328 samples from 308 Holstein Friesian dairy cows and in 284 samples from 38 female calves. We found that RLTL declines after birth but remains relatively stable in adult life. We also calculated the first heritability estimates of RLTL in a livestock species which were 0.38 (SE = 0.03) and 0.32 (SE = 0.08) for the cow and the calf dataset, respectively. RLTL measured at the ages of one and five years were positively correlated with productive lifespan (p < 0.05). We conclude that bovine RLTL is a heritable trait, and its association with productive lifespan may be used in breeding programmes aiming to enhance cow longevity.

Autophagy removes both functional and damaged intracellular macromolecules from cells via lysosomal degradation. Three autophagic mechanisms, namely macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy, have been described in mammals. Studies in experimental systems have found macroautophagy and CMA to decrease with normal aging, despite the fact that oxidative stress, which can activate both processes, increases with normal aging. Whether autophagic mechanisms decrease in the human brain during normal aging is unclear. The primary objective of this study was to examine the association of a major autophagy protein, lysosome-associated membrane glycoprotein (lamp2), with age in cerebrospinal fluid (CSF) samples from healthy subjects. Lamp2 consists of three isoforms, lamp2a, 2b and 2c, all of which participate in autophagy. Lamp2's CSF concentration decreases in Parkinson's disease (PD) and increases in Alzheimer's disease (AD), but whether its CSF concentration changes during normal aging has not been investigated. Our secondary objectives were to examine the associations of lamp2's CSF concentration with CSF levels of the molecular chaperone heat shock 70-kDa protein (HSPA8), which interacts with lamp2a in CMA, and oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO) and Total Antioxidant Capacity (TAC) in healthy subjects. We found lamp2's observed associations with these variables to be weak, with all Kendall's tau-b absolute values ≤0.20. These results suggest that CSF lamp2 concentration changes little during normal aging and does not appear to be associated with HSPA8 or oxidative stress. Further studies are indicated to determine the relationship between CSF lamp2 concentration and brain autophagic processes.

Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27). We also examined lamp2's correlations with age, oxidative stress, PD progression, and PD duration. Median lamp2 concentrations (pg/mL) were LRRK2 PD = 127, sPD = 333, CTL = 436, and LRRK2 CTL = 412. Log-transformed lamp2 concentrations, adjusting for gender effects (and excluding male LRRK2 PD patients because of low number), were lower in female LRRK2 PD patients than in LRRK2 CTL (p = 0.002) and CTL (p = 0.005) subjects (p = 0.06 for lamp2 comparison between female LRRK2 PD patients and sPD patients). Lamp2 did not appear to be associated with age, PD progression, or PD duration; however, three of four Spearman rho values for correlations between lamp2 and oxidative stress markers in PD subjects were ≥0.30. These findings suggest that CSF lamp2 concentrations may be decreased in female LRRK2 PD patients compared to healthy individuals with or without LRRK2 mutations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To measure the anterior nasal spine length (ANSL) and septal caudal extension (SCE), as well as assess the strength of association between these variables and tip projection in the Middle Eastern nose. Our secondary aim was to assess if columellar-labial angle (CLA) or columellar-spinal angle (CSA) vary as a function of ANSL and/or SCE., Study Design/setting: Prospective single institutional study., Subjects: Middle Eastern primary rhinoplasty patients without nasal trauma or prior endonasal surgical history., Methods: Photographic and intraoperative caliper measurements were used to determine Goode ratio (GR), CLA, CSA, ANSL, and SCE. Associations between numeric variables were examined with scatterplots, including use of LOWESS curves and Pearson correlation coefficients. Linear regression models were used for predicting quantitative variables (GR, CLA, CSA). Logistic regression models were used for predicting overprojection status based on GR., Results: In total, 102 patients met inclusion criteria (82 females, 20 males). Mean ANSL and SCE were 8.6 mm and 14.9 mm, respectively; ANSL and SCE had a strong positive association with each other. SCE and ANSL were found to have low predictability for GR, CLA, or CSA., Conclusion: Determinations of projection status using the GR method do not appear to be related to ANSL or SCE values in our Middle Eastern study group. Relationships of absolute columellar-labial or columellar-spinal angles are likely more complex than isolated value implications of SCE or ANSL., Competing Interests: Competing interests: None.

Background: Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy, suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer's disease (AD). The extent to which individuals with no cognitive impairment (NCI) possess serum anti-tau antibodies, and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment (MCI) or AD, are unclear. Previous studies measuring these antibodies did not account for antibody polyvalent binding, which can be extensive, nor that antibody binding to phosphorylated tau peptides could be due to binding to non-phosphorylated epitopes on those peptides., Methods: An ELISA controlling for these factors was used to measure the specific binding of serum IgG and IgM to phosphorylated ("pTau;" phosphorylated at Serine-199 and Serine-202) and non-phosphorylated ("non-pTau") tau 196-207 in subjects with NCI, MCI, or AD ( n  = 10/group). Between-group differences in these antibody levels were evaluated for statistical significance, and correlations were examined in pooled data from all subjects between these antibody levels and subject age, global cognitive functioning, and NFT counts., Results: Specific IgG binding to pTau and non-pTau was detected in all subjects except for one NCI control. Specific IgM binding was detected to pTau in all subjects except for two AD patients, and to non-pTau in all subjects. Mean pTau IgG was increased in MCI subjects by 53% and 70% vs. AD and NCI subjects respectively (both p  < 0.05), while no significant differences were found between groups for non-pTau IgG ( p  = 0.052), pTau IgM, or non-pTau IgM. Non-pTau IgG was negatively associated with global cognition (Spearman rho = -0.50)., Conclusions: Specific binding of serum IgG and IgM to phosphorylated and non-phosphorylated tau may be present in older persons regardless of their cognitive status. Serum IgG to phosphorylated tau may be increased in individuals with MCI, but this unexpected finding requires confirmation. The approach used in this study to measure specific serum antibodies to phosphorylated tau should be useful for measuring antibodies to other post-translationally-modified proteins that are of relevance to neurodegenerative disorders.

The objective of this study was to identify genomic regions and candidate genes associated with feed efficiency in lactating Holstein cows. In total, 4,916 cows with actual or imputed genotypes for 60,671 single nucleotide polymorphisms having individual feed intake, milk yield, milk composition, and body weight records were used in this study. Cows were from research herds located in the United States, Canada, the Netherlands, and the United Kingdom. Feed efficiency, defined as residual feed intake (RFI), was calculated within location as the residual of the regression of dry matter intake (DMI) on milk energy (MilkE), metabolic body weight (MBW), change in body weight, and systematic effects. For RFI, DMI, MilkE, and MBW, bivariate analyses were performed considering each trait as a separate trait within parity group to estimate variance components and genetic correlations between them. Animal relationships were established using a genomic relationship matrix. Genome-wide association studies were performed separately by parity group for RFI, DMI, MilkE, and MBW using the Bayes B method with a prior assumption that 1% of single nucleotide polymorphisms have a nonzero effect. One-megabase windows with greatest percentage of the total genetic variation explained by the markers (TGVM) were identified, and adjacent windows with large proportion of the TGVM were combined and reanalyzed. Heritability estimates for RFI were 0.14 (±0.03; ±SE) in primiparous cows and 0.13 (±0.03) in multiparous cows. Genetic correlations between primiparous and multiparous cows were 0.76 for RFI, 0.78 for DMI, 0.92 for MBW, and 0.61 for MilkE. No single 1-Mb window explained a significant proportion of the TGVM for RFI; however, after combining windows, significance was met on Bos taurus autosome 27 in primiparous cows, and nearly reached on Bos taurus autosome 4 in multiparous cows. Among other genes, these regions contain β-3 adrenergic receptor and the physiological candidate gene, leptin, respectively. Between the 2 parity groups, 3 of the 10 windows with the largest effects on DMI neighbored windows affecting RFI, but were not in the top 10 regions for MilkE or MBW. This result suggests a genetic basis for feed intake that is unrelated to energy consumption required for milk production or expected maintenance as determined by MBW. In conclusion, feed efficiency measured as RFI is a polygenic trait exhibiting a dynamic genetic basis and genetic variation distinct from that underlying expected maintenance requirements and milk energy output., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Visual Image analysis (VIA) of carcass traits provides the opportunity to estimate carcass primal cut yields on large numbers of slaughter animals. This allows carcases to be better differentiated and farmers to be paid based on the primal cut yields. It also creates more accurate genetic selection due to high volumes of data which enables breeders to breed cattle that better meet the abattoir specifications and market requirements. In order to implement genetic evaluations for VIA primal cut yields, genetic parameters must first be estimated and that was the aim of this study. Slaughter records from the UK prime slaughter population for VIA carcass traits was available from two processing plants. After edits, there were 17 765 VIA carcass records for six primal cut traits, carcass weight as well as the EUROP conformation and fat class grades. Heritability estimates after traits were adjusted for age ranged from 0.32 (0.03) for EUROP fat to 0.46 (0.03) for VIA Topside primal cut yield. Adjusting the VIA primal cut yields for carcass weight reduced the heritability estimates, with estimates of primal cut yields ranging from 0.23 (0.03) for Fillet to 0.29 (0.03) for Knuckle. Genetic correlations between VIA primal cut yields adjusted for carcass weight were very strong, ranging from 0.40 (0.06) between Fillet and Striploin to 0.92 (0.02) between Topside and Silverside. EUROP conformation was also positively correlated with the VIA primal cuts with genetic correlation estimates ranging from 0.59 to 0.84, whereas EUROP fat was estimated to have moderate negative correlations with primal cut yields, estimates ranged from -0.11 to -0.46. Based on these genetic parameter estimates, genetic evaluation of VIA primal cut yields can be undertaken to allow the UK beef industry to select carcases that better meet abattoir specification and market requirements.

Abattoir data are an important source of information for the genetic evaluation of carcass traits, but also for on-farm management purposes. The present study aimed to quantify the contribution of herd environment to beef carcass characteristics (weight, conformation score and fat score) with particular emphasis on generating finishing herd-specific profiles for these traits across different ages at slaughter. Abattoir records from 46,115 heifers and 78,790 steers aged between 360 and 900days, and from 22,971 young bulls aged between 360 and 720days, were analysed. Finishing herd-year and animal genetic (co)variance components for each trait were estimated using random regression models. Across slaughter age and gender, the ratio of finishing herd-year to total phenotypic variance ranged from 0.31 to 0.72 for carcass weight, 0.21 to 0.57 for carcass conformation and 0.11 to 0.44 for carcass fat score. These parameters indicate that the finishing herd environment is an important contributor to carcass trait variability and amenable to improvement with management practices., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro . We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients ( LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD.

Data collected from an experimental Holstein-Friesian research herd were used to determine genetic and phenotypic parameters of innate and adaptive cellular immune-associated traits. Relationships between immune-associated traits and production, health, and fertility traits were also investigated. Repeated blood leukocyte records were analyzed in 546 cows for 9 cellular immune-associated traits, including percent T cell subsets, B cells, NK cells, and granulocytes. Variance components were estimated by univariate analysis. Heritability estimates were obtained for all 9 traits, the highest of which were observed in the T cell subsets percent CD4 + , percent CD8 + , CD4 + :CD8 + ratio, and percent NKp46 + cells (0.46, 0.41, 0.43 and 0.42, respectively), with between-individual variation accounting for 59 to 81% of total phenotypic variance. Associations between immune-associated traits and production, health, and fertility traits were investigated with bivariate analyses. Strong genetic correlations were observed between percent NKp46 + and stillbirth rate (0.61), and lameness episodes and percent CD8 + (-0.51). Regarding production traits, the strongest relationships were between CD4 + :CD8 + ratio and weight phenotypes (-0.52 for live weight; -0.51 for empty body weight). Associations between feed conversion traits and immune-associated traits were also observed. Our results provide evidence that cellular immune-associated traits are heritable and repeatable, and the noticeable variation between animals would permit selection for altered trait values, particularly in the case of the T cell subsets. The associations we observed between immune-associated, health, fertility, and production traits suggest that genetic selection for cellular immune-associated traits could provide a useful tool in improving animal health, fitness, and fertility., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY 2.0 license (http://creativecommons.org/licenses/by/2.0/).)

Background: The significant social and economic loss as a result of bovine tuberculosis (bTB) presents a continuous challenge to cattle industries in the UK and worldwide. However, host genetic variation in cattle susceptibility to bTB provides an opportunity to select for resistant animals and further understand the genetic mechanisms underlying disease dynamics., Methods: The present study identified genomic regions associated with susceptibility to bTB using genome-wide association (GWA), regional heritability mapping (RHM) and chromosome association approaches. Phenotypes comprised de-regressed estimated breeding values of 804 Holstein-Friesian sires and pertained to three bTB indicator traits: i) positive reactors to the skin test with positive post-mortem examination results (phenotype 1); ii) positive reactors to the skin test regardless of post-mortem examination results (phenotype 2) and iii) as in (ii) plus non-reactors and inconclusive reactors to the skin tests with positive post-mortem examination results (phenotype 3). Genotypes based on the 50 K SNP DNA array were available and a total of 34,874 SNPs remained per animal after quality control., Results: The estimated polygenic heritability for susceptibility to bTB was 0.26, 0.37 and 0.34 for phenotypes 1, 2 and 3, respectively. GWA analysis identified a putative SNP on Bos taurus autosomes (BTA) 2 associated with phenotype 1, and another on BTA 23 associated with phenotype 2. Genomic regions encompassing these SNPs were found to harbour potentially relevant annotated genes. RHM confirmed the effect of these genomic regions and identified new regions on BTA 18 for phenotype 1 and BTA 3 for phenotypes 2 and 3. Heritabilities of the genomic regions ranged between 0.05 and 0.08 across the three phenotypes. Chromosome association analysis indicated a major role of BTA 23 on susceptibility to bTB., Conclusion: Genomic regions and candidate genes identified in the present study provide an opportunity to further understand pathways critical to cattle susceptibility to bTB and enhance genetic improvement programmes aiming at controlling and eradicating the disease.

Genetic evaluations for resistance to bovine tuberculosis (bTB) were calculated based on British national data including individual animal tuberculin skin test results, postmortem examination (presence of bTB lesions and bacteriological culture for Mycobacterium bovis), animal movement and location information, production history, and pedigree records. Holstein cows with identified sires in herds with bTB breakdowns (new herd incidents) occurring between the years 2000 and 2014 were considered. In the first instance, cows with a positive reaction to the skin test and a positive postmortem examination were defined as infected. Values of 0 and 1 were assigned to healthy and infected animal records, respectively. Data were analyzed with mixed models. Linear and logit function heritability estimates were 0.092 and 0.172, respectively. In subsequent analyses, breakdowns were split into 2-mo intervals to better model time of exposure and infection in the contemporary group. Intervals with at least one infected individual were retained and multiple intervals within the same breakdown were included. Healthy animal records were assigned values of 0, and infected records a value of 1 in the interval of infection and values reflecting a diminishing probability of infection in the preceding intervals. Heritability and repeatability estimates were 0.115 and 0.699, respectively. Reliabilities and across time stability of the genetic evaluation were improved with the interval model. Subsequently, 2 more definitions of "infected" were analyzed with the interval model: (1) all positive skin test reactors regardless of postmortem examination, and (2) all positive skin test reactors plus nonreactors with positive postmortem examination. Estimated heritability was 0.085 and 0.089, respectively; corresponding repeatability estimates were 0.701 and 0.697. Genetic evaluation reliabilities and across time stability did not change. Correlations of genetic evaluations for bTB with other traits in the current breeding goal were mostly not different from zero. Correlation with the UK Profitable Lifetime Index was moderate, significant, and favorable. Results demonstrated the feasibility of a national genetic evaluation for bTB resistance. Selection for enhanced resistance will have a positive effect on profitability and no antagonistic effects on current breeding goal traits. Official genetic evaluations are now based on the interval model and the last bTB trait definition., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

The effect of subclinical paratuberculosis (or Johne's disease) risk status on performance, health, and fertility was studied in 58,096 UK Holstein-Friesian cows with 156,837 lactations across lactations 1 to 3. Low-, medium-, and high-risk group categories were allocated to cows determined by a minimum of 4 ELISA milk tests taken at any time during their lactating life. Lactation curves of daily milk, protein, and fat yields and protein and fat percentage, together with log e -transformed somatic cell count, were estimated using a random regression model to quantify differences between risk groups. The effect of subclinical paratuberculosis risk groups on fertility, lactation-average somatic cell count, and mastitis were analyzed using linear regression fitting risk group as a fixed effect. Milk yield losses associated with high-risk cows compared with low-risk cows in lactations 1, 2, and 3 for mean daily yield were 0.34, 1.05, and 1.61kg; likewise, accumulated 305-d yields were 103, 316, and 485kg, respectively. The total loss was 904kg over the first 3 lactations. Protein and fat yield losses associated with high-risk cows were significant, but primarily a feature of decreasing milk yield. Similar trends were observed for both test-day and lactation-average somatic cell count measures with higher somatic cell counts from medium- and high-risk cows compared with low-risk cows, and differences were in almost all cases significant. Likewise, mastitis incidence was significantly higher in high-risk cows compared with low-risk cows in lactations 2 and 3. Whereas the few significant differences between risk groups among fertility traits were inconsistent with no clear trend. These results are expected to be conservative, as some animals that were considered negative may become positive after the timeframe of this study, particularly if the animal was tested when relatively young. However, the magnitude of milk yield losses together with higher somatic cell counts and an increase in mastitis incidence should motivate farmers to implement the appropriate control measures to reduce the spread of the disease., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain.

In pediatric office practices, we compared transcutaneous bilirubin levels in 689 newborns, age 3-10 days, with and without conjunctival icterus. In this age range, and in the absence of other clinical or laboratory indications, the presence of conjunctival icterus does not imply the need to measure the transcutaneous bilirubin or serum bilirubin level, but the absence of conjunctival icterus helps to rule out significant hyperbilirubinemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Livestock mature at different rates depending, in part, on their genetic merit; therefore, the optimal age at slaughter for progeny of certain sires may differ. The objective of the present study was to examine sire-level genetic profiles for carcass weight, carcass conformation, and carcass fat in cattle of multiple beef and dairy breeds, including crossbreeds. Slaughter records from 126,214 heifers and 124,641 steers aged between 360 and 1,200 d and from 86,089 young bulls aged between 360 and 720 d were used in the analysis; animals were from 15,127 sires. Variance components for each trait across age at slaughter were generated using sire random regression models that included quadratic polynomials for fixed and random effects; heterogeneous residual variances were assumed across ages. Heritability estimates across genders ranged from 0.08 (±0.02) to 0.34 (±0.02) for carcass weight, from 0.24 (±0.02) to 0.42 (±0.01) for conformation, and from 0.16 (±0.03) to 0.40 (±0.02) for fat score. Genetic correlations within each trait across ages weakened as the interval between ages compared lengthened but were all >0.64, suggesting a similar genetic background for each trait across different ages. Eigenvalues and eigenfunctions of the additive genetic covariance matrix revealed genetic variability among animals in their growth profiles for carcass traits, although most of the genetic variability was associated with the height of the growth profile. At the same age, a positive genetic correlation (0.60 to 0.78; SE ranged from 0.01 to 0.04) existed between carcass weight and conformation, whereas negative genetic correlations existed between fatness and both conformation (-0.46 to 0.08; SE ranged from 0.02 to 0.09) and carcass weight (-0.48 to -0.16; SE ranged from 0.02 to 0.14) at the same age. The estimated genetic parameters in the present study indicate genetic variability in the growth trajectory in cattle, which can be exploited through breeding programs and used in decision support tools.

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers. Two of these proteins, nuclear factor (erythroid-derived 2)-like 2 ("Nrf2") and heat shock 70 kDa protein 8 ("HSPA8"), were detected in preliminary ELISAs, then measured in a larger cohort (60 sPD, 10 LRRK2 + PD, 23 CTL, 31 LRRK2 + CTL). No statistically significant differences were found between the groups (Nrf2 p = 0.13, HSPA8 p = 0.21). Nrf2 concentrations in LRRK2 + PD subjects were strongly positively associated with Unified Parkinson's Disease Rating Scale (UPDRS) total and motor scores [Spearman rho = 0.77 (p = 0.012) and 0.83 (p = 0.005)] and negatively associated with Montreal Cognitive Assessment (MoCA) scores (rho = -0.57; p = 0.11). Partial correlation coefficient calculations indicated that disease duration contributed to the associations of Nrf2 levels with UPDRS scores and with MoCA scores in this group. While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation.

The therapeutic effects of intravenous immunoglobulin (IVIG) products were recently studied in Alzheimer's disease (AD) patients. Pilot studies produced encouraging results but phase II and III trials gave disappointing results; a further study is in progress. IVIG products contain antibodies to tau protein, the main component of neurofibrillary tangles (NFTs). The tau used to detect IVIG's anti-tau antibodies in previous studies was non-phosphorylated recombinant human tau-441, but NFT-associated tau is extensively phosphorylated. The objective of this study was to determine if various IVIG products contain specific antibodies to phosphorylated tau (anti-pTau antibodies). ELISAs were used to evaluate binding of six IVIG products to a 12 amino acid peptide, tau 196-207, which was phosphorylated ("pTau peptide") or non-phosphorylated ("non-pTau peptide") at Serine-199 and Serine-202. Both amino acid residues are phosphorylated in AD NFTs. Each IVIG's "anti-pTau antibody ratio" was calculated by dividing its binding to the pTau peptide by its binding to the non-pTau peptide. Seven experiments were performed and data were pooled, with each experiment contributing one data point from each IVIG product. Mean anti-pTau antibody ratios greater than 1.0, suggesting specific antibodies to phosphorylated tau, were found for three IVIG products. Because administration of antibodies to phosphorylated tau has been found to reduce tau-associated pathology in transgenic mouse models of tauopathy, increasing the levels of anti-pTau antibodies, together with other selected antibodies such as anti-Aβ, in IVIG might increase its ability to slow AD's progression., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A new breeding value that combines the amount of feed saved through improved metabolic efficiency with predicted maintenance requirements is described. The breeding value includes a genomic component for residual feed intake (RFI) combined with maintenance requirements calculated from either a genomic or pedigree estimated breeding value (EBV) for body weight (BW) predicted using conformation traits. Residual feed intake is only available for genotyped Holsteins; however, BW is available for all breeds. The RFI component of the "feed saved" EBV has 2 parts: Australian calf RFI and Australian lactating cow RFI. Genomic breeding values for RFI were estimated from a reference population of 2,036 individuals in a multi-trait analysis including Australian calf RFI (n=843), Australian lactating cow RFI (n=234), and UK and Dutch lactating cow RFI (n=958). In all cases, the RFI phenotypes were deviations from a mean of 0, calculated by correcting dry matter intake for BW, growth, and milk yield (in the case of lactating cows). Single nucleotide polymorphism effects were calculated from the output of genomic BLUP and used to predict breeding values of 4,106 Holstein sires that were genotyped but did not have RFI phenotypes themselves. These bulls already had BW breeding values calculated from type traits, from which maintenance requirements in kilograms of feed per year were inferred. Finally, RFI and the feed required for maintenance (through BW) were used to calculate a feed saved breeding value and expressed as the predicted amount of feed saved per year. Animals that were 1 standard deviation above the mean were predicted to eat 66 kg dry matter less per year at the same level of milk production. In a data set of genotyped Holstein sires, the mean reliability of the feed saved breeding value was 0.37. For Holsteins that are not genotyped and for breeds other than Holsteins, feed saved is calculated using BW only. From April 2015, feed saved has been included as part of the Australian national selection index, the Balanced Performance Index (BPI). Selection on the BPI is expected to lead to modest gains in feed efficiency., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objective: In infants <35 weeks' gestation, we sought to define the transcutaneous bilirubin (TcB) levels at which a total serum bilirubin (TSB) level suggesting the need for phototherapy is unlikely to occur and a TSB measurement can, therefore, be avoided., Study Design: Nursing staff performed 896 TcB measurements within 1 h of a TSB on 225 neonates 26 0/7-34 6/7 weeks' postmenstrual age (PMA). Generalized linear models were fit with generalized estimating equations (GEEs) to model the probability of having a TSB level at or above the phototherapy initiation cutpoint as a function of the TcB; these methods allow for multiple tests per infant., Results: The mean difference between TcB and TSB measurements was <1 mg dl(-1) for each PMA category. When the TcB was at least 3 mg dl(-1) below the TSB cutpoint for phototherapy, there was a ⩾98% probability that the TSB was not at, or above, the recommended phototherapy level. The single exception to this was a phototherapy level of 6 mg dl(-1) for infants of 28 0/7-29 6/7 weeks' PMA, where a TcB of 4 mg dl(-1) below the phototherapy level (ie a TcB ⩽2 mg dl(-1)) was necessary to achieve ⩾98% probability., Conclusion: Our data support the use of routine TcB screening for infants 28-34 6/7 weeks' gestation. TcB screening in the neonatal intensive care unit can identify infants who require a TSB to confirm or exclude the need for phototherapy.

The effects of intravenous immunoglobulin (IVIG) products were recently examined in patients with Alzheimer's disease (AD). Although encouraging results were obtained in pilot studies, later trials produced negative results. The rationale for these studies was that IVIG contains antibodies to amyloid-beta (Aβ). However, if Aβ anti-idiotypic antibodies (antibodies which bind to anti-Aβ antibodies) are present in IVIG or induced by its administration, these antibodies could potentially reduce its neuroprotective effects in AD. The objective of this study was to determine if IVIG contained such antibodies. Enzyme-linked immunosorbent assays (ELISAs) measured specific binding of IVIG Gamunex to purified human anti-Aβ IgG. The mean concentration of its Aβ anti-idiotypic antibodies in four experiments was 1.85 μg/mL (18.5 μg/g IgG; range = 1.82-1.89 μg/mL [18.2-18.9 μg/g IgG]), and their mean percentage of specific binding was 72.2% (range = 68.3-75.3%). We then performed ELISAs to determine if antibodies to purified human anti-Aβ were produced in C57BL/6 mice injected with the IVIG product Gammagard in an earlier study. After subtracting the expected immune response to normal human immunoglobulins, the median concentrations of these antibodies were 15.6 ng/mL (range = 1.2-108.2 ng/mL) in pre-treatment sera and 2419.4 ng/mL (range = 327.4-8478.4 ng/mL) in post-treatment sera. These results indicate that specific Aβ anti-idiotypic antibodies are detectable in IVIG and may be induced in mice by its administration. The presence of Aβ anti-idiotypic antibodies in IVIG products might decrease neuroprotective effects of their anti-Aβ antibodies in AD.

Introduction. To explore the long term incidence and predictors of incisional hernia in patients that had RARP. Methods. All patients who underwent RARP between 2003 and 2012 were mailed a survey reviewing hernia type, location, and repair. Results. Of 577 patients, 48 (8.3%) had a hernia at an incisional site (35 men had umbilical), diagnosed at (median) 1.2 years after RARP (mean follow-up of 5.05 years). No statistically significant differences were found in preoperative diabetes, smoking, pathological stage, age, intraoperative/postoperative complications, operative time, blood loss, BMI, and drain type between patients with and without incisional hernias. Incisional hernia patients had larger median prostate weight (45 versus 38 grams; P = 0.001) and a higher proportion had prior laparoscopic cholecystectomy (12.5% (6/48) versus 4.6% (22/480); P = 0.033). Overall, 4% (23/577) of patients underwent surgical repair of 24 incisional hernias, 22 umbilical and 2 other port site hernias. Conclusion. Incisional hernia is a known complication of RARP and may be associated with a larger prostate weight and history of prior laparoscopic cholecystectomy. There is concern about the underreporting of incisional hernia after RARP, as it is a complication often requiring surgical revision and is of significance for patient counseling before surgery.

Genetic improvement programs around the world rely on the collection of accurate phenotypic data. These phenotypes have an inherent value that can be estimated as the contribution of an additional record to genetic gain. Here, the contribution of phenotypes to genetic gain was calculated using traditional progeny testing (PT) and 2 genomic selection (GS) strategies that, for simplicity, included either males or females in the reference population. A procedure to estimate the theoretical economic contribution of a phenotype to a breeding program is described for both GS and PT breeding programs through the increment in genetic gain per unit of increase in estimated breeding value reliability obtained when an additional phenotypic record is added. The main factors affecting the value of a phenotype were the economic value of the trait, the number of phenotypic records already available for the trait, and its heritability. Furthermore, the value of a phenotype was affected by several other factors, including the cost of establishing the breeding program and the cost of phenotyping and genotyping. The cost of achieving a reliability of 0.60 was assessed for different reference populations for GS. Genomic reference populations of more sires with small progeny group sizes (e.g., 20 equivalent daughters) had a lower cost than those reference populations with either large progeny group sizes for fewer genotyped sires, or female reference populations, unless the heritability was large and the cost of phenotyping exceeded a few hundred dollars; then, female reference populations were preferable from an economic perspective., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The effects of intravenous immunoglobulin (IVIG) products are being evaluated in Alzheimer's disease (AD) patients. IVIG contains antibodies to tau protein, the main constituent of neurofibrillary tangles (NFTs). Tau has microtubule binding domain (MBD) repeats which are thought to be necessary for its aggregation, a key process in NFT formation. Tau's N-terminal region may also contribute to its aggregation and to the neurotoxicity of its soluble oligomers. This study examined the specific binding of IVIG products Gammagard, Gamunex, and Flebogamma to a tau N-terminal fragment (tau 45-73), tau's four MBD repeat sequences (tau 244-274, 275-305, 306-336, and 337-368), and a tau C-terminal fragment (tau 422-441). Mean antibody levels to tau 45-73 and tau 422-441 were significantly higher in Gamunex than in Gammagard and Flebogamma, while there were no significant differences between IVIG products for antibody concentrations to the MBD repeat sequences. Patterns of binding to tau fragments differed between IVIG products. Gammagard's highest binding was to tau 275-305 and tau 306-336 while Gamunex bound preferentially to tau 45-73 and tau 422-441. Flebogamma's binding to tau 275-305 and tau 306-336 was greater than to tau 337-368, and its binding to tau 306-336 was also higher than to tau 422-441. These findings indicate that IVIG products vary with respect to their binding to different regions of tau. This could result in differences with regard to their ability to prevent tau's aggregation and/or tau soluble oligomer neurotoxicity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Feed represents a large proportion of the variable costs in dairy production systems. The omission of feed intake measures explicitly from national dairy cow breeding objectives is predominantly due to a lack of information from which to make selection decisions. However, individual cow feed intake data are available in different countries, mostly from research or nucleus herds. None of these data sets are sufficiently large enough on their own to generate accurate genetic evaluations. In the current study, we collate data from 10 populations in 9 countries and estimate genetic parameters for dry matter intake (DMI). A total of 224,174 test-day records from 10,068 parity 1 to 5 records of 6,957 cows were available, as well as records from 1,784 growing heifers. Random regression models were fit to the lactating cow test-day records and predicted feed intake at 70 d postcalving was extracted from these fitted profiles. The random regression model included a fixed polynomial regression for each lactation separately, as well as herd-year-season of calving and experimental treatment as fixed effects; random effects fit in the model included individual animal deviation from the fixed regression for each parity as well as mean herd-specific deviations from the fixed regression. Predicted DMI at 70 d postcalving was used as the phenotype for the subsequent genetic analyses undertaken using an animal repeatability model. Heritability estimates of predicted cow feed intake 70 d postcalving was 0.34 across the entire data set and varied, within population, from 0.08 to 0.52. Repeatability of feed intake across lactations was 0.66. Heritability of feed intake in the growing heifers was 0.20 to 0.34 in the 2 populations with heifer data. The genetic correlation between feed intake in lactating cows and growing heifers was 0.67. A combined pedigree and genomic relationship matrix was used to improve linkages between populations for the estimation of genetic correlations of DMI in lactating cows; genotype information was available on 5,429 of the animals. Populations were categorized as North America, grazing, other low input, and high input European Union. Albeit associated with large standard errors, genetic correlation estimates for DMI between populations varied from 0.14 to 0.84 but were stronger (0.76 to 0.84) between the populations representative of high-input production systems. Genetic correlations with the grazing populations were weak to moderate, varying from 0.14 to 0.57. Genetic evaluations for DMI can be undertaken using data collated from international populations; however, genotype-by-environment interactions with grazing production systems need to be considered., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Validating genomic prediction equations in independent populations is an important part of evaluating genomic selection. Published genomic predictions from 2 studies on (1) residual feed intake and (2) dry matter intake (DMI) were validated in a cohort of 78 multiparous Holsteins from Australia. The mean realized accuracy of genomic prediction for residual feed intake was 0.27 when the reference population included phenotypes from 939 New Zealand and 843 Australian growing heifers (aged 5-8 mo) genotyped on high density (770k) single nucleotide polymorphism chips. The 90% bootstrapped confidence interval of this estimate was between 0.16 and 0.36. The mean realized accuracy was slightly lower (0.25) when the reference population comprised only Australian growing heifers. Higher realized accuracies were achieved for DMI in the same validation population and using a multicountry model that included 958 lactating cows from the Netherlands and United Kingdom in addition to 843 growing heifers from Australia. The multicountry analysis for DMI generated 3 sets of genomic predictions for validation animals, one on each country scale. The highest mean accuracy (0.72) was obtained when the genomic breeding values were expressed on the Dutch scale. Although the validation population used in this study was small (n=78), the results illustrate that genomic selection for DMI and residual feed intake is feasible. Multicountry collaboration in the area of dairy cow feed efficiency is the evident pathway to achieving reasonable genomic prediction accuracies for these valuable traits., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Intravenous immunoglobulin (IVIG) products are prepared from plasma immunoglobulins from healthy donors. Pilot studies suggest that IVIG may stabilize cognitive functioning in patients with mild-to-moderate Alzheimer's disease. This study measured antibodies to recombinant human tau protein in the IVIG products Gammagard (Baxter), Gamunex (Talecris), and Flebogamma (Grifols). Anti-tau antibodies were measured by ELISA, subtracting IVIG's polyvalent binding from its binding to tau-coated wells to calculate specific anti-tau antibody levels. Because polyvalent binding of IVIG products may interfere with ELISA measurement of their specific antibody levels, the percentage of binding of each IVIG product to tau-coated wells that was specific for tau was also determined. Specific anti-tau antibodies were detected in all three IVIG products, with significant differences between these products (p<0.001) even when Flebogamma's anti-tau antibodies were doubled to account for its preparation as a 5% solution vs. 10% solutions for Gammagard and Gamunex (means: Gammagard, 3.1 μg/ml; Gamunex, 2.5 μg/ml; Flebogamma, 1.2 μg/ml). The percentages of each IVIG product's specific binding to tau-coated wells also varied between the various products (p<0.001) and between all pairs of IVIG products (means: Gammagard, 73.1%; Flebogamma, 54.5%; Gamunex, 37.4%; p<0.01 for all pairwise comparisons). These findings indicate that IVIG products contain specific anti-tau antibodies. The concentrations of these antibodies and the percentages of specific binding of IVIG to tau-coated wells vary between IVIG products. Further studies are indicated to determine if IVIG also contains antibodies to pathologic forms of tau., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Intravenous immunoglobulin (IVIG) products are being investigated as possible therapeutic agents for mild cognitive impairment and Alzheimer's disease (AD). Anti-Aβ antibodies have been measured by ELISA in unfractionated IVIG products and in affinity-purified antibodies from these products, but it is unclear if similar results are obtained with these two approaches. Measurements of anti-Aβ antibodies in unfractionated IVIG may be confounded by the presence of polyvalent antibodies which can bind to multiple antigens, including those on ELISA plates; whether this is an issue when measuring anti-Aβ antibodies in purified antibody eluates from IVIG is also unknown. The objective of this study was to clarify these issues. The concentrations of specific antibodies to Aβ1-42 monomer and the percentages of specific binding to it were compared via ELISA between three unfractionated IVIG products (Gamunex [Talecris], Gammagard [Baxter], and Flebogamma [Grifols]) and their affinity-purified anti-Aβ antibodies. The concentrations of anti-Aβ antibodies in unfractionated IVIG products were higher than in their respective purified anti-Aβ eluates, and the rank order of the IVIG products with respect to their anti-Aβ concentrations differed between the two types of samples. The percentages of specific binding to Aβ were lower for unfractionated IVIG than for purified anti-Aβ eluates. These findings indicate that ELISA measurements of specific anti-Aβ antibodies and percentages of specific binding to Aβ produce different results depending upon whether these measurements are made in unfractionated IVIG products or their purified anti-Aβ antibodies. Polyvalent binding occurs even with purified anti-Aβ antibodies eluated from IVIG products, but it is less extensive than with unfractionated IVIG., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Detailed biological analyses (e.g. epidemiological, genetic) of animal health and fitness in the field are limited by the lack of large-scale recording of individual animals. An alternative approach is to identify immune traits that are associated with these important functions and can be subsequently used in more detailed studies. We have used an experimental dairy herd with uniquely dense phenotypic data to identify a range of potentially useful immune traits correlated with enhanced (or depressed) health and fitness. Blood samples from 248 dairy cows were collected at two-monthly intervals over a 10-month period and analysed for a number of immune traits, including levels of serum proteins associated with the innate immune response and circulating leukocyte populations. Immune measures were matched to individual cow records related to productivity, fertility and disease. Correlations between traits were calculated using bivariate analyses based on animal repeatability and random regression models with a Bonferroni correction to account for multiple testing. A number of significant correlations were found between immune traits and other recorded traits including: CD4(+):CD8(+) T lymphocyte ratio and subclinical mastitis; % CD8(+) lymphocytes and fertility; % CD335(+) natural killer cells and lameness episodes; and serum haptoglobin levels and clinical mastitis. Importantly these traits were not associated with reduced productivity and, in the case of cellular immune traits, were highly repeatable. Moreover these immune traits displayed significant between-animal variation suggesting that they may be altered by genetic selection. This study represents the largest simultaneous analysis of multiple immune traits in dairy cattle to-date and demonstrates that a number of immune traits are associated with health events. These traits represent useful selection markers for future programmes aimed at improving animal health and fitness.

As the emphasis in cattle breeding is shifting from traits that increase income toward traits that reduce costs, national breeding indices are expanding to include functional traits such as calving ease (CE). However, one issue is the lack of knowledge of genetic relationships between CE and other dairy traits. The same can be said about gestation length (GL), a potential novel selection trait with considerable heritabilities and possible genetic relationships with the calving process. This study aimed to estimate the genetic relationships between CE, GL, and other dairy traits of interest using a national data set of 31,053 primiparous cow performance records, as well as to separate direct and maternal genetic effects. Chosen dairy traits included fertility (calving interval, days to first service, nonreturn rate after 56 d, number of inseminations per conception), milk production (milk yield at d 110 in milk, accumulated 305-d milk yield, accumulated 305-d fat yield, accumulated 305-d protein yield), type (udder depth, chest width, rump width, rump angle, mammary composition, stature, body depth), and lifespan traits (functional days of productive life). To allow the separation of direct and maternal genetic effects, a random sire of the calf effect was included in the multi-trait linear trivariate sire models fitted using ASReml. Significant results showed that easily born individuals were genetically prone to high milk yield and reduced fertility in first lactation. Difficult calving primiparous cows were likely associated with being high-producing, wide and deep animals, with a reduced ability to subsequently conceive. Individuals that were born relatively early were associated with good genetic merit for milk production. Finally, individuals carrying their offspring longer were genetically associated with being wide and large animals that were themselves born relatively early. The study shows that it is feasible and valuable to separate direct and maternal effects when estimating genetic correlations between calving and other dairy traits. Furthermore, gestation length is best used as an indicator trait for lowly heritable calving traits, rather than as a novel selection trait. As estimated direct and maternal genetic correlations differ, we can conclude that genetic relationships between CE, GL, and traits of interest are present, but caution is required if these traits are implemented in national breeding indices., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to assess the impact of using different relative economic values (REVs) in selection indices on predicted financial and trait gains from selection of sires of cows and on the choice of leading Holstein bulls available in the UK dairy industry. Breeding objective traits were milk yield, fat yield, protein yield, lifespan, mastitis, non-return rate, calving interval and lameness. Relative importance of a trait, as estimated by a.h(2), was only moderately related to the rate of financial loss or total economic merit (ΔTEM) per percentage under- or overestimation of REV (r = 0.38 and 0.29, respectively) as a result of the variance-covariance structure of traits. The effects on TEM of under- or overestimating trait REVs were non-symmetrical. TEM was most sensitive to incorrect REVs for protein, fat, milk and lifespan and least sensitive to incorrect calving interval, lameness, non-return and mastitis REVs. A guide to deciding which dairy traits require the most rigorous analysis in the calculation of their REVs is given. Varying the REVs within a fairly wide range resulted in different bulls being selected by index and their differing predicted transmitting abilities would result in the herds moving in different directions in the long term (20 years). It is suggested that customized indices, where the farmer creates rankings of bulls tailored to their specific farm circumstances, can be worthwhile., (© 2012 Blackwell Verlag GmbH.)

α-Synuclein is thought to contribute to the pathogenesis of Parkinson's disease (PD). It is the main protein in Lewy bodies, the pathognomonic inclusion bodies in the PD substantia nigra, and mutations which increase its aggregation and/or expression are associated with familial early-onset parkinsonism. Soluble oligomers are considered to be α-synuclein's most neurotoxic conformation. We previously reported that intravenous immunoglobulin (IVIG) products contain specific antibodies to α-synuclein which do not prevent development of four-day α-synuclein oligomers. The objective of this study was to further examine IVIG's effects on α-synuclein's aggregation and neurotoxicity. The IVIG product Gammagard (Baxter Healthcare) did not prevent the development of nine-day α-synuclein oligomers, nor did it degrade preformed oligomers, as shown by western blots performed on gels run under reducing/denaturing conditions and native gels. In western blots of native gels, an additional low molecular weight band (~22 kDa) was detected in α-synuclein incubated for four days in Gammagard, but not in Gammagard alone. No significant differences were found for Thioflavin-T reactivity between α-synuclein amorphous aggregates grown in Gammagard vs. those grown in phosphate-buffered saline. Gammagard partially protected SK-N-BE(2)M17 human neuroblastoma cells against α-synuclein oligomer toxicity (p = 0.007 vs. protective effects of normal human IgG). These findings suggest that although IVIG does not prevent α-synuclein aggregation, it still may reduce α-synuclein neurotoxicity through an unknown mechanism., (Copyright © 2012 Elsevier B.V. All rights reserved.)