The HSPB1-p62/SQSTM1 functional complex regulates the unconventional secretion and transcellular spreading of the HD-associated mutant huntingtin protein.

Conformational diseases, such as Alzheimer, Parkinson and Huntington diseases, are part of a common class of neurological disorders characterized by the aggregation and progressive accumulation of proteins bearing aberrant conformations. Huntington disease (HD) has autosomal dominant inheritance and is caused by mutations leading to an abnormal expansion in the polyglutamine (polyQ) tract of the huntingtin (HTT) protein, leading to the formation of HTT inclusion bodies in neurons of affected patients. Interestingly, recent experimental evidence is challenging the conventional view by which the disease pathogenesis is solely a consequence of the intracellular accumulation of mutant protein aggregates. These studies reveal that transcellular transfer of mutated huntingtin protein is able to seed oligomers involving even the wild-type (WT) forms of the protein. To date, there is still no successful strategy to treat HD. Here, we describe a novel functional role for the HSPB1-p62/SQSTM1 complex, which acts as a cargo loading platform, allowing the unconventional secretion of mutant HTT by extracellular vesicles. HSPB1 interacts preferentially with polyQ-expanded HTT compared with the WT protein and affects its aggregation. Furthermore, HSPB1 levels correlate with the rate of mutant HTT secretion, which is controlled by the activity of the PI3K/AKT/mTOR signalling pathway. Finally, we show that these HTT-containing vesicular structures are biologically active and able to be internalized by recipient cells, therefore providing an additional mechanism to explain the prion-like spreading properties of mutant HTT. These findings might also have implications for the turn-over of other disease-associated, aggregation-prone proteins.

Point prevalence audit surveys of respiratory tract infection consultations and antibiotic prescribing in primary care before and during the COVID-19 pandemic in Ireland.

BACKGROUND: Respiratory tract infections (RTIs) are the most common reason for prescribing antibiotics in general practice. The COVID-19 pandemic has impacted on antibiotic prescribing and delivery of primary care in Ireland. OBJECTIVES: To assess the quality of antibiotic prescribing, the impact of the COVID-19 pandemic and identify opportunities for antimicrobial stewardship (AMS) in Ireland. METHODS: Point prevalence audit surveys for RTI consultations were conducted as part of a European study at three time periods: January-February 2020, March-May 2020 and March-May 2021. Antibiotic prescribing was assessed and comparisons made between the three time periods. RESULTS: In total, 765 consultations were recorded, which were mainly face to face before the pandemic, but changed to predominantly remote consultations during the pandemic surveys in 2020 and 2021 (82% and 75%). Antibiotics were prescribed in 54% of RTI consultations before the pandemic. During pandemic surveys, this dropped to 23% in 2020 and 21% in 2021. There was a decrease in prescribing of Red (reserve) agents in 2021. Assessment against indication-specific quality indicators showed a high proportion of consultations for bronchitis and tonsillitis resulting in an antibiotic prescription (67% and 85%). Point-of-care testing (POCT) to aid diagnosis of RTIs were utilized in less than 1% of consultations. CONCLUSIONS: During the COVID-19 pandemic, there was a reduction in antibiotic prescribing. Opportunities identified to support AMS in primary care in Ireland are targeted initiatives to reduce antibiotic prescribing for bronchitis and tonsillitis and introducing POCT to support appropriate antibiotic prescribing.

[Dental care avoidance: catering to four different subtypes of patients]. / Zorgmijdende patiënten: benadering voor 4 subtypen van patiënten.

Only too often, it is automatically assumed that dental checkups or treatments are avoided by a subset of the patient population out of fear. To put it more correctly: to avoid the anxiety associated with dental appointments - anxiety believed to be based on fear of pain and pain increase. Following this assumption, three other subtypes of avoidant patients are being overlooked. These are care-avoiders with fear caused by trauma, self-effacing behavior or depression. Well-informed questions can initiate an understanding conversation which can break and stop this care-avoiding behavior. Patients can be referred to the general practitioner (formental health care), or to special dentistry, in more complex cases.

[Persistent physical symptoms with a focus on pain in the head and neck area]. / Aanhoudende lichamelijke klachten met een focus op pijn in het hoofd-halsgebied.

In every dental practice, patients present with persistent physical symptoms. Such complaints can significantly complicate dental treatment, especially if they are not acknowledged, or if the patient feels they are not being taken seriously. For this reason, it is important to increase oral care providers' knowledge and expertise concerning persistent physical symptoms in a broader sense and in the head and neck area in particular, with the aim of improving the treatment alliance and to increase the effectiveness of dental treatment.

Quality indicators for hospital antimicrobial stewardship programmes: a systematic review.

BACKGROUND: Measuring the quality and effectiveness of antimicrobial stewardship (AMS) programmes with quality indicators (QIs) is an area of increasing interest. We conducted a systematic review to identify QIs of AMS programmes in the hospital setting and critically appraise their methodological quality. METHODS: We searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CINAHL, Scopus/web of science databases and the grey literature for studies that defined and/or described the development process and characteristics of the QIs developed. The Appraisal of Indicators through Research and Evaluation (AIRE) instrument was used to critically appraise the methodological quality of the QI sets. RESULTS: We identified 16 studies of QI sets consisting of 229 QIs. The QI sets addressed a broad range of areas of AMS in the hospital setting and consisted of 75% process indicators, 24% structural indicators and 1% outcome indicators. There was a wide variation in the information and level of detail presented describing the methodological characteristics of the QI sets identified. CONCLUSIONS: The QIs identified in this study focused on process and structural indicators with few outcome indicators developed-a major deficiency in this area. Future research should focus on the development of outcome indicators or the use of process or structural indicators linked to outcomes to assess AMS. Testing of the QIs in practice is an essential methodological element of the QI development process and should be included in the QI development study or as planned validation work.

Rumen function and grazing behavior of early-lactation dairy cows supplemented with fodder beet.

Fodder beet (FB) is a source of readily fermentable carbohydrate that can mitigate early spring herbage deficits and correct the negative energy balance experienced during early lactation in pastoral dairy systems of New Zealand. However, the low-fiber and high-soluble carbohydrate content of both FB bulb and spring herbage are factors that promote subacute ruminal acidosis, impairing rumen function and limiting the marginal milk production response to supplement. In a crossover experiment, 8 Holstein Friesian × Jersey early-lactation dairy cows were used to test the effect of supplementing 16 kg of dry matter (DM) of a grazed perennial ryegrass herbage with 6 kg of DM/d of FB bulb (FBH) versus herbage only (HO) on changes in rumen function and grazing behavior. Following 20 d of adaptation to diets, DM disappearance (%) of FB bulb (FBH cows only) and herbage were measured in sacco, separately. Cows were fasted overnight, and the ruminal contents were bailed the following morning (~0930 h) again to determine the pool size of volatile fatty acids, ammonia, and particle size of digesta, as well as to estimate the rate of ruminal outflow and degradation of neutral detergent fiber. The FBH diet did not alter DM intake, milk yield, or milk solid (fat + protein) production compared with HO. Supplementation of herbage with FB reduced ruminal pH compared with HO between ~0800 h and 1300 h each day. During each period, 1 cow experienced severe subacute ruminal acidosis (pH <5.6 for >180 min/d) during final adaptation to the target FB allocation. The FBH diet reduced the ruminal pool of acetate and ammonia, but increased the ruminal pool of butyrate and lactate compared with HO. When fed FB, rumination and grazing time increased and grazing intensity declined compared with cows fed HO. Despite increased rumination, the comminution of large particles declined 28% between the first and second rumen bailing when cows were fed FB, and in sacco DM disappearance of perennial ryegrass declined 18% compared with cows fed HO. These results indicate that grazing dairy cows supplemented with FB (40% of daily intake) increase rumination and mastication intensity to counteract reduced ruminal degradation of ryegrass herbage due to low ruminal fluid pH.

Genomic analyses for predicted milk fatty acid composition throughout lactation in North American Holstein cattle.

Milk fat composition has important implications in the nutritional and processing properties of milk. Additionally, milk fat composition is associated with cow physiological and health status. The main objectives of this study were (1) to estimate genetic parameters for 5 milk fatty acid (FA) groups (i.e., short-chain, medium-chain, long-chain, saturated, and unsaturated) predicted from milk infrared spectra using a large data set; (2) to predict genomic breeding values using a longitudinal single-step genomic BLUP approach; and (3) to conduct a single-step GWAS aiming to identify genomic regions, candidate genes, and metabolic pathways associated with milk FA, and consequently, to understand the underlying biology of these traits. We used 629,769 test-day records of 201,465 first-parity Holstein cows from 6,105 herds. A total of 8,865 genotyped (Illumina BovineSNP50K BeadChip, Illumina, San Diego, CA) animals were considered for the genomic analyses. The average daily heritability ranged from 0.24 (unsaturated FA) to 0.47 (medium-chain and saturated FA). The reliability of the genomic breeding values ranged from 0.56 (long-chain fatty acid) to 0.74 (medium-chain fatty acid) when using the default τ and ω scaling parameters, whereas it ranged from 0.58 (long-chain fatty acid) to 0.73 (short-chain fatty acid) when using the optimal τ and ω values (i.e., τ = 1.5 and ω = 0.6), as defined in a previous study in the same population. Relevant chromosomal regions were identified in Bos taurus autosomes 5 and 14. The proportion of the variance explained by 20 adjacent single nucleotide polymorphisms ranged from 0.71% (saturated FA) to 15.12% (long-chain FA). Important candidate genes and pathways were also identified. In summary, our results contribute to a better understanding of the genetic architecture of predicted milk FA in dairy cattle and reinforce the relevance of using genomic information for genetic analyses of these traits.

Short communication: Time-dependent genetic parameters and single-step genome-wide association analyses for predicted milk fatty acid composition in Ayrshire and Jersey dairy cattle.

Milk fat content and fatty acid (FA) composition have great economic value to the dairy industry as they are directly associated with taste and chemical-physical characteristics of milk and dairy products. In addition, consumers' choices are not only based on the nutritional aspects of food, but also on products known to promote better health. Milk FA composition is also related to the metabolic status and physiological stages of cows and thus can also be used as indicator for other novel traits of interest (e.g., metabolic diseases and methane yield). Genetic selection is a promising alternative to manipulate milk FA composition. In this study, we aimed to (1) estimate time-dependent genetic parameters for 5 milk FA groups (i.e., short-chain, medium-chain, long-chain, saturated, and unsaturated) predicted based on milk mid-infrared spectroscopy, for Canadian Ayrshire and Jersey breeds, and (2) conduct a time-dependent, single-step genome-wide association study to identify genomic regions, candidate genes, and metabolic pathways associated with milk FA. We analyzed 31,709 test-day records of 9,648 Ayrshire cows from 268 herds, and 34,341 records of 11,479 Jersey cows from 883 herds. The genomic database contained a total of 2,330 Ayrshire and 1,019 Jersey animals. The average daily heritability ranged from 0.18 (long-chain FA) to 0.34 (medium-chain FA) in Ayrshire, and from 0.25 (long-chain and unsaturated FA) to 0.52 (medium-chain and saturated FA) in Jersey. Important genomic regions were identified in Bos taurus autosomes BTA3, BTA5, BTA12, BTA13, BTA14, BTA16, BTA18, BTA20, and BTA21. The proportion of the variance explained by 20 adjacent SNP ranged from 0.71% (saturated FA) to 1.11% (long-chain FA) in Ayrshire, and from 0.70% (unsaturated FA) to 3.09% (medium-chain FA) in Jersey cattle. Important candidate genes and pathways were also identified, such as the PTK2 and TRAPPC9 genes, associated with milk fat percentage, and HMGCS, FGF10, and C6 genes, associated with fertility traits and immune response. Our findings on the genetic parameters and candidate genes contribute to a better understanding of the genetic architecture of milk FA composition in Ayrshire and Jersey dairy cattle.

Symposium review: Multiple-trait single-step genomic evaluation for hoof health.

Hoof lesions represent an important issue in modern dairy herds, with reported prevalence in different countries ranging from 40 to 70%. This high prevalence of hoof lesions has both economic and social consequences, resulting in increased labor expenses and decreasing animal production, longevity, reproduction, health, and welfare. Therefore, a key goal of dairy herds is to reduce the incidence of hoof lesions, which can be achieved both by improving management practices and through genetic selection. The Canadian dairy industry has recently released a hoof health sub-index. This national genetic evaluation program for hoof health was achieved by creating a centralized data collection system that routinely transfers data recorded by hoof trimmers into a coherent and sustainable national database. The 8 most prevalent lesions (digital dermatitis, interdigital dermatitis, interdigital hyperplasia, heel horn erosion, sole hemorrhage, sole ulcer, toe ulcer, and white line lesion) in Canada are analyzed with a multiple-trait model using a single-step genomic BLUP method. Estimated genomic breeding values for each lesion are combined into a sub-index according to their economic value and prevalence. In addition, data recorded within this system were used to create an interactive management report for dairy producers by Canadian DHI, including the prevalence of lesions on farm, their trends over time, and benchmarks with provincial and national averages.

An investigation of the effects of procalcitonin testing on antimicrobial prescribing in respiratory tract infections in an Irish university hospital setting: a feasibility study.

BACKGROUND: Diagnostic uncertainty and a high prevalence of viral infections present unique challenges for antimicrobial prescribing for respiratory tract infections (RTIs). Procalcitonin (PCT) has been shown to support prescribing decisions and reduce antimicrobial use safely in patients with RTIs, but recent study results have been variable. METHODS: We conducted a feasibility study of the introduction of PCT testing in patients admitted to hospital with a lower RTI to determine if PCT testing is an effective and worthwhile intervention to introduce to support the existing antimicrobial stewardship (AMS) programme and safely decrease antimicrobial prescribing in patients admitted with RTIs. RESULTS: A total of 79 patients were randomized to the intervention PCT-guided treatment group and 40 patients to the standard care respiratory control group. The addition of PCT testing led to a significant decrease in duration of antimicrobial prescriptions (mean 6.8 versus 8.9 days, P = 0.012) and decreased length of hospital stay (median 7 versus 8 days, P = 0.009) between the PCT and respiratory control group. PCT did not demonstrate a significant reduction in antimicrobial consumption when measured as DDDs and days of therapy. CONCLUSIONS: PCT testing had a positive effect on antimicrobial prescribing during this feasibility study. The successful implementation of PCT testing in a randomized controlled trial requires an ongoing comprehensive education programme, greater integration into the AMS programme and delivery of PCT results in a timely manner. This feasibility study has shown that a larger randomized controlled trial would be beneficial to further explore the positive aspects of these findings.

Nonlinear optical memory effect.

Light propagating through random media produces characteristic speckle patterns, directly related to the large multitude of scattering events. These complex dynamics remarkably display robustness to perturbation of the incoming light parameters, maintaining correlation in the scattered wavefront. This behavior is known as the optical memory effect. Here we unveil the properties of the nonlinear optical memory effect, which occurs when an optothermal nonlinearity perturbs the random material. The effect is characterized through a series of pump and probe experiments in silica aerogel, in the visible range. This additional degree of freedom further generalizes the memory effect, opening the road to applications based on the nonlinear response of random media.

Genome-wide association analysis for ß-hydroxybutyrate concentration in Milk in Holstein dairy cattle.

BACKGROUND: Ketosis in dairy cattle has been shown to cause a high morbidity in the farm and substantial financial losses to dairy farmers. Ketosis symptoms, however, are difficult to identify, therefore, the amount of ketone bodies (mainly ß-hydroxybutyric acid, BHB) is used as an indicator of subclinical ketosis in cows. It has also been shown that milk BHB concentrations have a strong correlation with ketosis in dairy cattle. Mid-infrared spectroscopy (MIR) has recently became a fast, cheap and high-throughput method for analyzing milk components. The aim of this study was to perform a genome-wide association study (GWAS) on the MIR-predicted milk BHB to identify genomic regions, genes and pathways potentially affecting subclinical ketosis in North American Holstein dairy cattle. RESULTS: Several significant regions were identified associated with MIR-predicted milk BHB concentrations (indicator of subclinical ketosis) in the first lactation (SCK1) and second and later lactations (SCK2) in Holstein dairy cows. The strongest association was located on BTA6 for SCK1 and BTA14 on SCK2. Several SNPs on BTA6 were identified in regions and variants reported previously to be associated with susceptibility to ketosis and clinical mastitis in Jersey and Holstein dairy cattle, respectively. One highly significant SNP on BTA14 was found within the DGAT1 gene with known functions on fat metabolism and inflammatory response in dairy cattle. A region on BTA6 and three SNPs on BTA20 were found to overlap between SCK1 and SCK2. However, a novel region on BTA20 (55-63 Mb) for SCK2 was also identified, which was not reported in previous association studies. Enrichment analysis of the list of candidate genes within the identified regions for MIR-predicted milk BHB concentrations yielded molecular functions and biological processes that may be involved in the inflammatory response and lipid metabolism in dairy cattle. CONCLUSIONS: The results of this study confirmed several SNPs and genes identified in previous studies as associated with ketosis susceptibility and immune response, and also found a novel region that can be used for further analysis to identify causal variations and key regulatory genes that affect clinical/ subclinical ketosis.

Modeling portal-drained viscera and liver fluxes of essential amino acids in dairy cows.

The objective of this work was to predict essential amino acid (EAA) use and release by the portal-drained viscera (PDV) and liver of dairy cows. Previously derived equations were tested using data assembled from the literature, refit to the data, and modifications were undertaken to determine the best model for each EAA. The refitted model has the same structure as the original equations but is parameterized using a database of group means, as the original equations were derived using a single study with individual cow data and found to be biased. The PDV clearance model predicted portal vein concentrations given inputs of absorbed and arterial fluxes of EAA with root mean squared errors (RMSE) ranging from 3.3 to 12.1% of the observed means, and concordance correlation coefficients (CCC) ranging from 0.86 to 0.99 when using previously reported parameters. The reparameterized model generated from the assembled data set resulted in predictions of EAA portal vein concentrations with RMSE ranging from 3.2 to 8.6% and CCC ranging from 0.93 to 1.00. Slope bias ranged from 12.4 to 55.3% of mean squared errors and was correlated with arterial EAA concentrations. Modifying the model to allow rate constants to vary as a function of arterial EAA concentrations reduced slope bias, resulting in RMSE ranging from 1.9 to 6.5% and CCC from 0.97 to 1.00. Alternatively, splitting the model to account for use of EAA from absorption separately from arterial use resulted in poorer predictions and biologically infeasible parameter estimates. The liver clearance model predicted hepatic vein concentrations from arterial and portal vein input fluxes with RMSE across EAA ranging from 1.9 to 6.8% and CCC ranging from 0.97 to 1.00 when using reported parameters. The reparameterized model generated from the assembled data set resulted in predictions of EAA hepatic vein concentrations with RMSE ranging from 1.9 to 6.7% and CCC ranging from 0.97 to 1.00. Significant slope bias was present for Arg, His, Lys, Phe, Thr, and Val. Altering the model to represent the clearance rate constant as a function of arterial concentrations resulted in RMSE ranging from 1.8 to 6.5% and CCC ranging from 0.97 to 1.00. The combination of PDV and liver clearance models provided predictions of total splanchnic use similar to those of an empirical model representing splanchnic use as a fractional proportion of absorption that had RMSE ranging from 3.0 to 8.6% and CCC ranging from 0.95 to 0.99, with significant slope bias for the majority of EAA.

Predictions of ruminal outflow of essential amino acids in dairy cattle.

The objective of this work was to update and evaluate predictions of essential AA (EAA) outflows from the rumen. The model was constructed based on previously derived equations for rumen-undegradable (RUP), microbial (MiCP), and endogenous (EndCP) protein outflows from the rumen, and revised estimates of ingredient composition and EAA composition of the protein fractions. Corrections were adopted to account for incomplete recovery of EAA during 24-h acid hydrolysis. The predicted ruminal protein and EAA outflows were evaluated against a data set of observed values from the literature. Initial evaluations indicated a minor mean bias for non-ammonia, non-microbial nitrogen flow ([RUP + EndCP]/6.25) of 16 g of N per day. Root mean squared errors (RMSE) of EAA predictions ranged from 26.8 to 40.6% of observed mean values. Concordance correlation coefficients (CCC) of EAA predictions ranged from 0.34 to 0.55. Except for Leu, all ruminal EAA outflows were overpredicted by 3.0 to 32 g/d. In addition, small but significant slope biases were present for Arg [2.2% mean squared error (MSE)] and Lys (3.2% MSE). The overpredictions may suggest that the mean recovery of AA from acid hydrolysis across laboratories was less than estimates encompassed in the recovery factors. To test this hypothesis, several regression approaches were undertaken to identify potential causes of the bias. These included regressions of (1) residual errors for predicted EAA flows on each of the 3 protein-driven EA flows, (2) observed EAA flows on each protein-driven EAA flow, including an intercept, (3) observed EAA flows on the protein-driven EAA flows, excluding an intercept term, and (4) observed EAA flows on RUP and MiCP. However, these equations were deemed unsatisfactory for bias adjustment, as they generated biologically unfeasible predictions for some entities. Future work should focus on identifying the cause of the observed prediction bias.

Assessing bioavailability of ruminally protected methionine and lysine prototypes.

Met and Lys are essential AA that can limit lactational performance in dairy cattle fed protein-sufficient diets. Thus, there is industry demand for ruminally protected (RP) sources of Met and Lys. One method of providing ruminal protection for Met and Lys is lipid encapsulation. The objective of this work was to assess 3 lipid-encapsulated Met prototypes (P1, P2, and P3) and 1 Lys prototype (P4) to determine ruminal protection, small intestine absorption (experiment 1), and animal production responses (experiment 2). Ruminal protection was estimated from 8-h in situ retention during ruminal incubation and intestinal absorption from plasma appearance after an abomasal bolus of the in situ retentate. Blood samples were collected over time to determine plasma Met and Lys concentration responses compared with unprotected Lys and Met infused abomasally. The prototypes were not exposed to the total diet or subjected to typical feed handling methods before evaluation. The bioavailability of P1, P2, and P3 Met prototypes was found to be 14, 21, and 18% of the initial AA material, respectively. The RP-Lys prototype had a bioavailability of 45%. To evaluate production responses, 20 Holstein cows were randomly assigned to 2 trials (n = 10 each) in a replicated Latin square design with 14-d periods. The base diet was predicted to be deficient in metabolizable Met (-14.8 g/d) and Lys (-16.1 g/d) per the Cornell Net Carbohydrate and Protein System (version 6.55). In the Met trial, the base diet was supplemented with RP-Lys to meet Lys requirements, and treatments were as follows: no added RP-Met (NCM), NCM plus Smartamine M (SM; Adisseo, Alpharetta, GA), and NCM plus P1, P2, or P3 at 148% of the Met content of SM. In the Lys trial, the base diet was supplemented with RP-Met to meet the Met requirement, and treatments were as follows: no added Lys (NCL), NCL plus AjiProL (AL; Ajinomoto Heartland Inc., Chicago, IL), and NCL plus P4 at 55, 78, or 102% of the reported absorbed Lys in AL. All products were top dressed on the diet without prior mixing or extended exposure to the rest of the diet. Milk protein concentration significantly increased when diets were supplemented with P2, P3, or SM (3.12, 3.12, and 3.11%, respectively) compared with NCM (3.02%). Only P1 (3.04%) was significantly lower than SM. Prototype P2 had the greatest numerical milk protein output response among the 3 RP-Met prototypes, suggesting that it may have had the greatest efficacy when supplemented into these rations. There was a numerical milk protein concentration response to AL and a linear increase in milk protein concentration for P4. The P4 and AL treatments resulted in comparable milk protein production regardless of P4 dose.

Symposium review: The choice and collection of new relevant phenotypes for fertility selection.

In dairy production, high fertility contributes to herd profitability by achieving greater production and maintaining short calving intervals. Improved management practices and genetic selection have contributed to reversing negative trends in dairy cow fertility, but further progress is still required. Phenotypes included in current genetic evaluations are largely interval and binary traits calculated from insemination and calving date records. Several indicator traits such as calving, health, variation in body condition score, and longevity traits also apply to genetic improvement of fertility. Several fertility traits are included in the selection indices of many countries, but for improved selection, the development of novel phenotypes that more closely describe the physiology of reproduction and limit management bias could be more effective. Progesterone-based phenotypes can be determined from milk samples to describe the heritable interval from calving to corpus luteum activity, as well as additional measures of cow cyclicity. A fundamental component of artificial insemination practices is the observation of estrus. Novel phenotypes collected on estrous activity could be used to select for cows clearly displaying heat, as those cows are more likely to be inseminated at the right time and therefore have greater fertility performance. On-farm technologies, including in-line milk testing and activity monitors, may allow for phenotyping novel traits on large numbers of animals. Additionally, selection for improved fertility using traditional traits could benefit from refined and accurate recording and implementation of parameters such as pregnancy confirmation and reproductive management strategy, to differentiate embryonic or fetal loss, and to ensure selection for reproductive capability without producer intervention. Opportunities exist to achieve genetic improvement of reproductive efficiency in cattle using novel phenotypes, which is required for long-term sustainability of the dairy cattle population and industry.

A landscape of the heritability of Fourier-transform infrared spectral wavelengths of milk samples by parity and lactation stage in Holstein cows.

Fourier-transform near- and mid-infrared (FTIR) milk spectral data are routinely collected in many countries worldwide. Establishing an optimal strategy to use spectral data in genetic evaluations requires knowledge of the heritabilities of individual FTIR wavelength absorbances. Previous FTIR heritability estimates have been based on relatively small sample sizes and have not considered the possibility that heritability may vary across parities and stages of the lactation. We used data from ∼370,000 test-day records of Canadian Holstein cows to produce a landscape of the heritability of FTIR spectra, 1,060 wavelengths in the near- and mid-infrared spectrum (5,011-925 cm-1), by parity and month of the lactation (mo 1 to 3 and mo 1 to 6, respectively). The 2 regions of the spectrum associated with absorption of electromagnetic energy by water molecules were estimated to have very high phenotypic variances, very low heritabilities, and very low proportion of variance explained by herd-year-season (HYS) subclasses. The near- or short-wavelength infrared (SWIR: 5,066-3,672 cm-1) region was also characterized by low heritability estimates, whereas the estimated proportion of the variance explained by HYS was high. The mid-wavelength infrared region (MWIR: 3,000-2,500 cm-1) and the transition between mid and long-wavelength infrared region (MWIR-LWIR: 1,500-925 cm-1) harbor several waves characterized by moderately high (≥0.4) heritabilities. Most of the high-heritability regions contained wavelengths that are reported to be associated with important milk metabolites and components. Interestingly, these 2 same regions tended to show more variability in heritabilities between parity and lactation stage. Second parity showed heritability patterns that were distinctly different from those of the first and third parities, whereas the first 2 mo of the lactation had clearly distinct heritability patterns compared with mo 3 to 6.

A systematic approach to map the adolescent human papillomavirus vaccine decision and identify intervention strategies to address vaccine hesitancy.

OBJECTIVES: Unsubstantiated safety concerns with human papillomavirus (HPV) vaccines continue to linger. This study sought to identify factors that influence the adolescent HPV vaccine decision and systematically identify intervention functions and strategies likely to be effective in reducing vaccine hesitancy. STUDY DESIGN: This is a qualitative focus group study. METHODS: Focus groups were conducted with female adolescents (aged 14-16 years) in Cork and Kerry. During focus groups, the trained facilitator used a semistructured, Theoretical Domains Framework (TDF)-based topic guide to prompt discussion. Transcripts were thematically analysed using the TDF and Behaviour Change Wheel. Behaviour Change Technique Taxonomy version 1 was used to suggest intervention functions and strategies for addressing HPV vaccine hesitancy. RESULTS: A total of 50 adolescents (96% vaccinated), participated in 10 focus groups. The key themes were presented by means of the relevant TDF domains. Seven domains were selected as the most relevant: knowledge, social influences, beliefs about capabilities, optimism, beliefs about consequences, emotion and environmental context and resources. Five intervention functions were identified, education, persuasion, enablement, modelling and environmental restructuring, and linked to 11 relevant Behaviour Change Technique (BCTs). Potential intervention strategies were developed. CONCLUSIONS: This study provided a detailed insight into behavioural factors influencing the vaccine decision-making process. It was identified that awareness and knowledge about HPV and its health sequelae was low. Lack of information is a well-recognised determinant of vaccine hesitancy. Therefore, education was recommended as a key area to address in future intervention studies.

Genetic correlations of mid-infrared-predicted milk fatty acid groups with milk production traits.

The objective of this research was to estimate the genetic correlations between milk mid-infrared-predicted fatty acid groups and production traits in first-parity Canadian Holsteins. Contents of short-chain, medium-chain, long-chain, saturated, and unsaturated fatty acid groupings in milk samples can be predicted using mid-infrared spectral data for cows enrolled in milk recording programs. Predicted fatty acid group contents were obtained for 49,127 test-day milk samples from 10,029 first-parity Holstein cows in 810 herds. Milk yield, fat and protein yield, fat and protein percentage, fat-to-protein ratio, and somatic cell score were also available for these test days. Genetic parameters were estimated for the fatty acid groups and production traits using multiple-trait random regression test day models by Bayesian methods via Gibbs sampling. Three separate 8- or 9-trait analyses were performed, including the 5 fatty acid groups with different combinations of the production traits. Posterior standard deviations ranged from <0.001 to 0.01. Average daily genetic correlations were negative and similar to each other for the fatty acid groups with milk yield (-0.62 to -0.59) and with protein yield (-0.32 to -0.25). Weak and positive average daily genetic correlations were found between somatic cell score and the fatty acid groups (from 0.25 to 0.36). Stronger genetic correlations with fat yield, fat and protein percentage, and fat-to-protein ratio were found with medium-chain and saturated fatty acid groups compared with those with long-chain and unsaturated fatty acid groups. Genetic correlations were very strong between the fatty acid groups and fat percentage, ranging between 0.88 for unsaturated and 0.99 for saturated fatty acids. Daily genetic correlations from 5 to 305 d in milk with milk, protein yield and percentage, and somatic cell score traits showed similar patterns for all fatty acid groups. The daily genetic correlations with fat yield at the beginning of lactation were decreasing for long-chain and unsaturated fatty acid groups and increasing for short-chain fatty acids. Genetic correlations between fat percentage and fatty acids were increasing at the beginning of lactation for short- and medium-chain and saturated fatty acids, but slightly decreasing for long-chain and unsaturated fatty acid groups. These results can be used in defining fatty acid traits and breeding objectives.

Standardization of milk infrared spectra for the retroactive application of calibration models.

The objective of this study was to standardize the infrared spectra obtained over time and across 2 milk laboratories of Canada to create a uniform historical database and allow (1) the retroactive application of calibration models for prediction of fine milk composition; and (2) the direct use of spectral information for the development of indicators of animal health and efficiency. Spectral variation across laboratories and over time was inspected by principal components analysis (PCA). Shifts in the PCA scores were detected over time, leading to the definition of different subsets of spectra having homogeneous infrared signal. To evaluate the possibility of using common equations on spectra collected by the 2 instruments and over time, we developed a standardization (STD) method. For each subset of data having homogeneous infrared signal, a total of 99 spectra corresponding to the percentiles of the distribution of the absorbance at each wavenumber were created and used to build the STD matrices. Equations predicting contents of saturated fatty acids, short-chain fatty acids, and C18:0 were created and applied on different subsets of spectra, before and after STD. After STD, bias and root mean squared error of prediction decreased by 66% and 32%, respectively. When calibration equations were applied to the historical nonstandardized database of spectra, shifts in the predictions could be observed over time for all investigated traits. Shifts in the distribution of the predictions over time corresponded to the shifts identified by the inspection of the PCA scores. After STD, shifts in the predicted fatty acid contents were greatly reduced. Standardization reduced spectral variability between instruments and over time, allowing the merging of milk spectra data from different instruments into a common database, the retroactive use of calibrations equations, or the direct use of the spectral data without restrictions.