What makes a temperate phage an effective bacterial weapon?

Temperate bacteriophages (phages) are common features of bacterial genomes and can act as self-amplifying biological weapons, killing susceptible competitors and thus increasing the fitness of their bacterial hosts (lysogens). Despite their prevalence, however, the key characteristics of an effective temperate phage weapon remain unclear. Here, we use systematic mathematical analyses coupled with experimental tests to understand what makes an effective temperate phage weapon. We find that effectiveness is controlled by phage life history traits-in particular, the probability of lysis and induction rate-but that the optimal combination of traits varies with the initial frequency of a lysogen within a population. As a consequence, certain phage weapons can be detrimental when their hosts are rare yet beneficial when their hosts are common, while subtle changes in individual life history traits can completely reverse the impact of an individual phage weapon on lysogen fitness. We confirm key predictions of our model experimentally, using temperate phages isolated from the clinically relevant Liverpool epidemic strain of Pseudomonas aeruginosa. Through these experiments, we further demonstrate that nutrient availability can also play a critical role in driving frequency-dependent patterns in phage-mediated competition. Together, these findings highlight the complex and context-dependent nature of temperate phage weapons and the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly. IMPORTANCE: Temperate bacteriophages-viruses that integrate within bacterial DNA-are incredibly common within bacterial genomes and can act as powerful self-amplifying weapons. Bacterial hosts that carry temperate bacteriophages can thus gain a fitness advantage within a given niche by killing competitors. But what makes an effective phage weapon? Here, we first use a simple mathematical model to explore the factors determining bacteriophage weapon utility. Our models suggest that bacteriophage weapons are nuanced and context-dependent; an individual bacteriophage may be beneficial or costly depending upon tiny changes to how it behaves or the bacterial community it inhabits. We then confirm these mathematical predictions experimentally, using phages isolated from cystic fibrosis patients. But, in doing so, we also find that another factor-nutrient availability-plays a key role in shaping bacteriophage-mediated competition. Together, our results provide new insights into how temperate bacteriophages modulate bacterial communities.

Osteoarthritis year in review 2022: rehabilitation.

This year in review presents key highlights from research relating to osteoarthritis (OA) rehabilitation published from the 1st April 2021 to the 18th March 2022. To identify studies for inclusion in the review, an electronic database search was carried out in Medline, Embase and CINAHLplus. Following screening, included studies were grouped according to their predominant topic area, including core OA rehabilitation treatments (education, exercise, weight loss), adjunctive treatments, novel and emerging treatments or research methods, and translation of rehabilitation evidence into practice. Studies of perceived high clinical importance, quality, or controversy in the field were selected for inclusion in the review. Headline findings include: the positive role of technology to support remote delivery of core OA rehabilitation treatments, the importance of delivering educational interventions alongside exercise, the clinical and cost-effectiveness of a stepped approach to exercise, controversy around the potential mechanisms of action of exercise, mixed findings regarding the use of splinting for thumb base OA, increasing research on blood flow restriction training as a potential new intervention for OA, and evidence that the beneficial effects from core OA treatments seen in randomised controlled trials can be seen when implemented in clinical practice. A consistent finding across several recently published systematic reviews is that randomised controlled trials testing OA rehabilitation interventions are often small, with some risk of bias. Whilst future research is warranted, it needs to be large scale and robust, to enable definitive answers to important remaining questions in the field of OA rehabilitation.

Motivation to train during a pandemic: The role of fitness resources, mental health, and motivational profiles among student-athletes in team sports.

The sporting season across post-secondary institutions was canceled in March 2020 due to COVID-19, and student-athletes had to maintain their training at home. It is unclear what personal and contextual factors facilitated student-athletes' ability to maintain their training routines at home when social distancing and lockdown (SD/L) policies were put in place. Our cross-sectional study of 433 student-athletes examined (a) how athletes adapted their training, (b) what training barriers they experienced, (c) whether motivational profiles were associated with differences in training behaviors and mental health, and (d) what variables predicted athletes' motivation to train during this prolonged offseason. Student-athletes across Canada were recruited to complete an online survey between August and September 2020. Results showed that athletes significantly reduced their training load and intensity, with approximately 25% exercising two or fewer days a week. Barriers to training included limited access to fitness resources and equipment, having inconsistent training schedules, and experiencing emotional distractions, with some of these barriers more common among female athletes than male athletes. For motivation profiles, athletes with higher levels of intrinsic motivation tended to maintain the intensity of their workouts and experienced lower mood disturbance. A hierarchical multiple regression revealed that being male, being younger, having higher levels of intrinsic and introjected motivation, having access to fitness resources, maintaining a steady training schedule, having fewer emotional distractions, and lower mood disturbance were significant predictors to being motivated to train during the pandemic. We discuss strategies coaches and trainers can implement to best support their student-athletes.

International Foot and Ankle Osteoarthritis Consortium review and research agenda for diagnosis, epidemiology, burden, outcome assessment and treatment.

OBJECTIVE: To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research. METHOD: Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0 = not at all important to 100 = extremely important). Items scoring a mean of 70 or above were selected for inclusion. RESULTS: Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold: three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment. CONCLUSIONS: Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Triggers for acute flare in adults with, or at risk of, knee osteoarthritis: a web-based case-crossover study in community-dwelling adults.

OBJECTIVE: To identify proximate causes ('triggers') of flares in adults with, or at risk of, knee osteoarthritis (OA), estimate their course and consequences, and determine higher risk individuals. METHODS: In this 13-week web-based case-crossover study adults aged ≥40 years, with or without a recorded diagnosis of knee OA, and no inflammatory arthropathy who self-reported a knee flare completed a questionnaire capturing information on exposure to 21 putative activity-related, psychosocial and environmental triggers (hazard period, ≤72 h prior). Comparisons were made with identical exposure measurements at four 4-weekly scheduled time points (non-flare control period) using conditional logistic regression. Flare was defined as a sudden onset of worsening signs and symptoms, sustained for ≥24 h. Flare characteristics, course and consequence were analysed descriptively. Associations between flare frequency and baseline characteristics were estimated using Poisson regression. RESULTS: Of 744 recruited participants (mean age [SD] 62.1 [10.2] years; 61% female), 376 reported 568 flares (hazards) and provided 867 valid control period measurements. Thirteen exposures (eight activity-related, five psychosocial/environmental) were positively associated with flare onset within 24 h (strongest odds ratio estimate, knee buckling: 9.06: 95% confidence interval [CI] 5.86, 13.99; weakest, cold/damp weather: 1.45: 95%CI 1.12, 1.87). Median flare duration was 5 days (IQR 3, 8), less common if older (incident rate ratio [IRR] 0.98: 95%CI 0.97, 0.99), more common if female (IRR 1.85: 95%CI 1.43, 2.39). CONCLUSIONS: Multiple activity-related, psychosocial and environmental exposures are implicated in triggering flares. This evidence can help inform prevention and acute symptom management for patients and clinicians.

Partial budget analysis of culture- and algorithm-guided selective dry cow therapy.

The objectives of this study were to (1) use partial budget analysis to estimate the cash impact for herds that switch from blanket dry cow therapy (BDCT) to culture- or algorithm-guided selective dry cow therapy (SDCT) and (2) conduct a sensitivity analysis to investigate effects in situations where SDCT increased clinical and subclinical mastitis risk during the subsequent lactation. A partial budget model was created using Monte Carlo simulation with @Risk software. Expenditures associated with dry-off procedures and health outcomes (clinical and subclinical mastitis) during the first 30 d in milk were used to model herd-level effects, expressed in units of US dollars per cow dry-off. Values for each economic component were derived from findings from a recent multisite clinical trial, peer-reviewed journal articles, USDA databases, and our experiences in facilitating the implementation of SDCT on farms. Fixed values were used for variables expected to have minimal variation within the US dairy herd population (e.g., cost of rapid culture plates) and sampling distributions were used for variables that were hypothesized to vary enough to effect the herd net cash impact of one or more DCT approach(es). For Objective 1, herd-level udder health was assumed to be unaffected by the implementation of SDCT. For culture-guided SDCT, producers could expect to save an average of +$2.14 (-$2.31 to $7.23 for 5th and 95th percentiles) per cow dry-off as compared with BDCT, with 75.5% of iterations being ≥$0.00. For algorithm-guided SDCT, the mean net cash impact was +$7.85 ($3.39-12.90) per cow dry-off, with 100% of iterations being ≥$0.00. The major contributors to variance in cash impact for both SDCT approaches were percent of quarters treated at dry-off and the cost of dry cow antibiotics. For Objective 2, we repeated the partial budget model with the 30-d clinical and subclinical mastitis incidence increasing by 1, 2, and 5% (i.e., risk difference = 0.01, 0.02, and 0.05) in both SDCT groups compared with BDCT. For algorithm-guided SDCT, average net cash impacts were ≥$0.00 per cow dry-off (i.e., cost effective) when mastitis incidence increased slightly. However, as clinical mastitis incidence increased, economic returns for SDCT diminished. These findings indicate that when SDCT is implemented appropriately (i.e., no to little negative effect on health), it might be a cost-effective practice for US herds under a range of economic conditions.

Osteoarthritis year in review 2020: epidemiology & therapy.

This personal choice of research themes and highlights from within the past year (1 May 2019 to 14 April 2020) spans descriptive, analytical-observational, and intervention studies. Descriptive estimates of the burden of osteoarthritis continue to underscore its position as a leading cause of disability worldwide, but whose burden is often felt greatest among disadvantaged and marginalised communities. Many of the major drivers of that burden are known but epidemiological studies continue the important work of elaborating on their timing, dose, specificity, and reversibility and placing them within an appropriate multi-level framework. A similar process of elaboration is seen also in studies (re-)estimating the relative benefits and risks of existing interventions, in some cases helping to identify low-value care, unwarranted variation, and initiating processes of deprescribing and decommissioning. Such research need not engender therapeutic nihilism. Our review closes by highlighting some emerging evidence on the efficacy and safety of novel therapeutic interventions and with a selective roll-call of methodological and meta-research in OA illustrating the continued commitment to improving research quality.

Effect of reproductive management programs for first service on replacement dairy heifer economics.

Our objective was to evaluate cash flow for dairy heifers managed for first service with programs that relied primarily on insemination at detected estrus (AIE), timed AI (TAI), or a combination of both. Holstein heifers from 2 commercial farms were randomized to receive first service with sexed semen after the beginning of the AI period (AIP) at 12 mo of age with 1 of 3 treatments: (1) PGF+AIE (n = 317): AIE after PGF2α injections every 14 d (up to 3) starting at the beginning of the AIP; heifers not AIE 9 d after the third PGF2α were enrolled in the 5d-Cosynch (5dCP) protocol; (2) ALL-TAI (n = 315): TAI after ovulation synchronization with the 5dCP protocol; and (3) PGF+TAI (n = 334): AIE after 2 PGF2α injections 14 d apart (second PGF2α at beginning of AIP). If not AIE 9 d after the second PGF2α, the 5dCP protocol was used for TAI. After first service heifers were AIE or received TAI after the 5dCP with conventional semen. Individual heifer cash flow (CF) for up to a 15-mo period (d 0 = beginning of AIP) was calculated using reproductive cost (rearing only), feed cost (rearing only), income over feed cost (lactation only), calf value, operating cost, and with or without replacement cost. A stochastic analysis with Monte Carlo simulation was used to estimate differences in CF for a range of market values for inputs and outputs. Time to pregnancy for up to 100 d after the beginning of the AIP was analyzed by Cox's proportional regression, binary data with logistic regression, and continuous outcomes by ANOVA. Time to pregnancy (hazard ratio and 95% CI) was reduced for the ALL-TAI versus the PGF+AIE treatment (1.20; 1.02-1.42), but it was similar for ALL-TAI and PGF+TAI (1.13; 0.95-1.33) and the PGF+AIE and PGF+TAI treatments (1.07; 0.91-1.25). The proportion of heifers not pregnant by 100 d did not differ (PGF+AIE = 7.0%; PGF+TAI = 6.5%; ALL-TAI = 6.8%). When including replacement cost, CF ($/slot per 15 mo) differences were $51 and $42 in favor of the PGF+TAI and ALL-TAI compared with the PGF+AIE treatment, and $9 in favor of the PGF+TAI compared with the ALL-TAI treatment but did not differ statistically. Excluding heifers that were replaced to evaluate the effect of timing of pregnancy differences only, the difference in CF between the PGF+AIE with the PGF+TAI and ALL-TAI treatment was the same (i.e., $15) and favored the programs that used more TAI, but also did not differ statistically. Stochastic simulation results were in line with those of the deterministic analysis confirming the benefit of the programs that used more TAI. We concluded that submission of heifers for first service with TAI only or TAI in combination with AIE generated numerical differences in CF of potential value to commercial dairy farms. Reduced rearing cost and increased revenue during lactation increased CF under fixed (not statistically significant) or simulated variable market conditions.

Randomized controlled non-inferiority trial investigating the effect of 2 selective dry-cow therapy protocols on antibiotic use at dry-off and dry period intramammary infection dynamics.

Selective dry-cow therapy (SDCT) could be used to reduce antibiotic use on commercial dairy farms in the United States but is not yet widely adopted, possibly due to concerns about the potential for negative effects on cow health. The objective of this study was to compare culture- and algorithm-guided SDCT programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure, non-inferiority trial for the following quarter-level outcomes: antibiotic use at dry-off, dry period intramammary infection (IMI) cure risk, dry period new IMI risk, and IMI risk at 1 to 13 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by treating only quarters from which aseptically collected milk samples tested positive on the Minnesota Easy 4Cast plate (University of Minnesota, St. Paul, MN) after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow had either a Dairy Herd Improvement Association test somatic cell count >200,000 cells/mL during the current lactation or 2 or more clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Intramammary infection status at enrollment and at 1 to 13 DIM was determined using standard bacteriological methods. The effect of treatment group on dry period IMI cure, dry period new IMI, and IMI risk at 1 to 13 DIM was determined using generalized linear mixed models (logistic), with marginal standardization to derive risk difference (RD) estimates. Quarter-level antibiotic use at dry-off for each group was BDCT (100%), cult-SDCT (45%), and alg-SDCT (45%). The crude dry period IMI cure risk for all quarters was 87.5% (818/935), the crude dry period new IMI risk was 20.1% (764/3,794), and the prevalence of IMI at 1 to 13 DIM was 23% (961/4,173). Non-inferiority analysis indicated that culture- and algorithm-guided SDCT approaches performed at least as well as BDCT for dry period IMI cure risk. In addition, the final models indicated that the risks for each of the 3 IMI measures were similar between all 3 treatment groups (i.e., RD estimates and 95% confidence intervals all close to 0). These findings indicate that under the conditions of this trial, culture- and algorithm-guided SDCT can substantially reduce antibiotic use at dry-off without negatively affecting IMI dynamics.

Randomized controlled trial investigating the effect of 2 selective dry-cow therapy protocols on udder health and performance in the subsequent lactation.

The objective of this study was to compare culture- and algorithm-guided selective dry-cow therapy (SDCT) programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure clinical trial for the following cow-level outcomes: clinical mastitis, removal from the herd, and Dairy Herd Improvement Association (DHIA) test-day milk yield and SCC measures during the first 120 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by only treating quarters from which aseptically collected milk samples tested positive on a rapid culture system after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow met at least one of the following criteria: (1) any DHIA test with a somatic cell count >200,000 cells/mL during the current lactation, and (2) ≥2 clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Clinical mastitis and removal from the herd events (i.e., culling or death) and DHIA test-day data from dry-off to 120 DIM were extracted from herd records. Hazard ratios (HR) for the effect of treatment group on clinical mastitis and removal from the herd during 1 to 120 DIM were determined using Cox proportional hazards regression. The effects of treatment group on test-day loge-transformed SCC and milk yield were determined using linear mixed models. Final models indicated that either SDCT program was unlikely to increase clinical mastitis risk (HRcult-SDCT/BDCT = 0.82, 95% CI: 0.58, 1.15; HRalg-SDCT/BDCT = 0.83, 95% CI: 0.63, 1.09) or test-day logeSCC (cult-SDCT minus BDCT = 0.05, 95% CI: -0.09, 0.18; alg-SDCT minus BDCT = 0.07, 95% CI: -0.07, 0.21). Risk of removal from the herd and test-day milk yield were similar between treatment groups. Findings from this study indicate that culture- or algorithm-guided SDCT can be used at dry-off without negatively affecting cow health and performance in early lactation.

A consensus-based framework for conducting and reporting osteoarthritis phenotype research.

BACKGROUND: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. METHODS: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. RESULTS: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. CONCLUSIONS: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.

A reproductive management program aimed at increasing reinsemination of nonpregnant dairy cows at detected estrus resulted in similar reproductive performance to a program that favored timed artificial insemination.

The objective of this experiment was to compare time to pregnancy and proportion of cows not pregnant 210 d after first service for cows managed for second and subsequent artificial insemination (AI) services with a reproductive management program that promoted reinsemination at detected estrus (AIE) or a program that promoted timed AI (TAI). After first service, lactating Holstein cows were blocked by parity and randomly assigned to d 32 Resynch (D32R; n = 464) or AIE Resynch (AIER; n = 512). To determine the effect of management strategies on time to pregnancy and cows not pregnant by the end of a 210 d at-risk period after first AI service, cows remained in AIER and D32R until pregnancy or herd exit. Cows in D32R received a GnRH treatment 32 ± 3 d after AI (first treatment intervention; FTI). Nonpregnancy diagnosis was conducted 7 d later by transrectal ultrasonography when nonpregnant cows with a corpus luteum (CL) ≥15 mm completed the Resynch protocol (PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) and cows without a CL (NoCL cows) were enrolled in a PreG-Ovsynch protocol (GnRH, 7 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h TAI) to receive TAI. For the AIER treatment, nonpregnant cows with a CL ≥15 mm observed by transrectal ultrasonography 32 ± 3 d after AI (i.e., FTI) received PGF2α to induce estrus. Cows not AIE within 7 d were enrolled in Resynch (GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h TAI). Cows in the NoCL group in AIER were enrolled in PreG-Ovsynch. Detection of estrus was performed based on visual observation of behavioral signs of estrus and tail-paint removal. Binomial data were analyzed with logistic regression and time to event data with Cox's proportional regression. After the FTI, a greater proportion of cows were AIE in AIER than D32R (36.0 vs. 11.9%) and more cows were AIE within 7 d of the FTI for AIER (25.0%) than D32R (4.8%). Overall pregnancy per AI at 68 ± 3 d after AI did not differ (AIER = 35.5% vs. D32R = 34.7%). The hazard of pregnancy up to 210 d after first AI for all cows enrolled (hazard ratio = 1.04, 95% CI 0.90 to 1.19) and for cows that received treatments only (D32R = 308, AIER = 349; hazard ratio = 1.00, 95% CI 0.85 to 1.19) did not differ. We conclude that a program aimed at increasing the proportion of cows reinseminated at detected estrus by treatment with PGF2α at 32 ± 3 d after AI may be an alternative strategy for dairy farms that prefer or need to inseminate more cows at detected estrus rather than by TAI.

Midfoot osteoarthritis: potential phenotypes and their associations with demographic, symptomatic and clinical characteristics.

OBJECTIVE: To investigate the demographic, symptomatic, clinical and structural foot characteristics associated with potential phenotypes of midfoot osteoarthritis (OA). DESIGN: Cross-sectional study of 533 community-dwelling adults aged ≥50 years with foot pain in the past year. Health questionnaires and clinical assessments of symptoms, foot structure and function were undertaken. Potential midfoot OA phenotypes were defined by the pattern of radiographic joint involvement affecting either the medial midfoot (talonavicular, navicular-1st cuneiform, or cuneiform-1st metatarsal joint), central midfoot (2nd cuneiform-metatarsal joint), or both medial and central midfoot joints. Multivariable regression models with generalised estimating equations were used to investigate the associations between patterns of midfoot joint involvement and symptomatic, clinical and structural characteristics compared to those with no or minimal midfoot OA. RESULTS: Of 879 eligible feet, 168 had medial midfoot OA, 103 central midfoot OA, 76 both medial and central midfoot OA and 532 no/minimal OA. Having both medial and central midfoot OA was associated with higher pain scores, dorsally-located midfoot pain (OR 2.54, 95%CI 1.45, 4.45), hallux valgus (OR 1.76, 95%CI 1.02, 3.05), flatter foot posture (ß 0.44, 95%CI 0.12, 0.77), lower medial arch height (ß 0.02, 95%CI 0.01, 0.03) and less subtalar inversion and 1st MTPJ dorsiflexion. Isolated medial midfoot OA and central midfoot OA had few distinguishing clinical characteristics. CONCLUSIONS: Distinct phenotypes of midfoot OA appear challenging to identify, with substantial overlap in symptoms and clinical characteristics. Phenotypic differences in symptoms, foot posture and function were apparent in this study only when both the medial and central midfoot were involved.

Reproductive performance of replacement dairy heifers submitted to first service with programs that favor insemination at detected estrus, timed artificial insemination, or a combination of both.

Our objective was to compare the insemination dynamics and time to pregnancy for up to 100 d after the beginning of the artificial insemination period (AIP) for heifers managed with first artificial insemination (AI) service programs that relied primarily on insemination at detected estrus (AIE) after PGF2α treatments, timed artificial insemination (TAI), or a combination of both. Holstein heifers were randomly assigned to receive first AI service with sex-selected semen after 368 ± 10 d of age with (1) AIE after synchronization of estrus with up to 3 PGF2α treatments every 14 d starting on the first day of the AIP (PGF+AIE; n = 317). Heifers not AIE up to 9 d after the third PGF2α received a 5-d Cosynch protocol with progesterone supplementation [GnRH + controlled internal drug release insert (CIDR)-5 d-CIDR removal and PGF2α-3 d-GnRH and TAI] before TAI. Heifers detected in estrus from CIDR removal and PGF2α until the day before TAI received AIE with no GnRH treatment; (2) 2 PGF2α treatments 14 d apart with the second treatment at the beginning of the AIP (PGF+TAI; n = 334). Heifers received AIE for up to 9 d after the second PGF2α treatment. Heifers not AIE received TAI after the 5-d Cosynch protocol and (3) TAI after the 5-d Cosynch protocol (ALL-TAI; n = 315). Heifers failing to conceive to a previous AI received a subsequent AI with conventional semen at detected estrus or TAI after the 5-d Cosynch protocol. Binomial outcomes were analyzed by logistic regression, whereas time to AI and pregnancy were analyzed with Cox's regression. The hazard of first AI up to 45 d of the AIP was greater for ALL-TAI than for PGF+AIE [hazard ratio (HR) = 1.72; 95% confidence interval (CI) =1.45 to 2.03] and PGF+TAI (HR = 1.51; 95% CI = 1.28 to 1.77), but similar for PGF+AIE and PGF+TAI (HR = 1.14; 95% CI = 0.97 to 1.33). A greater proportion of heifers received AIE in PGF+AIE (98.7%) than in PGF+TAI (78.5%). Overall, first service pregnancy per AI did not differ (PGF+AIE = 42.0%; PGF+TAI = 47.3%, ALL-TAI = 43.8%). Time to pregnancy was reduced for ALL-TAI compared with PGF+AIE (HR = 1.20, 95% CI = 1.02 to 1.42), but was similar to that of PGF+TAI (HR = 1.13, 95% CI = 0.96 to 1.33). Time to pregnancy did not differ for PGF+AIE and PGF+TAI (HR = 1.07, 95% CI = 0.91 to 1.25). Median days to pregnancy were 27, 23, and 21 for heifers in PGF+AIE, PGF+TAI, and ALL-TAI, respectively. We concluded that an ALL-TAI program for first service reduced time to pregnancy, albeit a relatively small reduction, when compared with a program that relied primarily on AIE after induction of estrus with PGF2α treatments. The program that combined synchronization of estrus and TAI (PGF+TAI) resulted in similar time to pregnancy than the predominant TAI and predominant AIE programs.

Differential effects of a single dose of oral calcium based on postpartum plasma calcium concentration in Holstein cows.

Our objectives were to determine (1) the effect of a single dose of an oral Ca bolus within 24 h after parturition on plasma Ca concentration, (2) the response of primiparous (PP) and multiparous (MP) cows to this supplementation strategy, and (3) differential responses based on plasma Ca at enrollment. For objective 1, cows from 1 commercial dairy in New York State were enrolled within 19 h after parturition (mean ± standard deviation = 8.3 ± 5.3 h) and randomized within parity group (first, second, and ≥third) to control [CON (n = 25); no placebo] or a single dose bolus treatment [BOL (n = 25); 3 oral Ca boluses supplying 54 to 64 g of Ca]. Plasma Ca was measured repeatedly between 1 and 24 h following treatment. For objectives 2 and 3, cows on 6 commercial farms in New York State were assigned to treatment as for objective 1 (CON, n = 1,973; BOL, n = 1,976). Herd records for health, reproduction, and Dairy Herd Improvement Association test day milk production were collected. Mixed effect multivariable models were developed using repeated measures ANOVA, Poisson regression, or proportional hazard models. Objective 2 analyses considered treatment with periparturient risk factors, whereas objective 3 analyses also considered Ca status. No difference was observed for plasma Ca between 1 and 24 h after treatment. Primiparous cows assigned to BOL calving at >712 d old had decreased risk of one or more health disorders [≤30 d in milk; risk ratio (RR) = 0.65, 95% confidence interval (CI) = 0.51 to 0.84] and those with body condition score >3.5 responded to BOL with increased milk production (CON = 31.7 ± 1.1, BOL = 35.1 ± 1.1 kg/d), as did those with days carried calf >277 (CON = 31.9 ± 1.0, BOL = 34.7 ± 1.0 kg/d). Reduced risk of one or more health disorders was observed in parity ≥3 (RR = 0.85, 95% CI = 0.81 to 0.89) and MP cows with body condition score >3.5 (retained placenta; RR = 0.70, 95% CI = 0.58 to 0.84) or that were lame (displaced abomasum; RR = 0.49, 95% CI = 0.32 to 0.75). Differential responses for PP cows by Ca status were minimal. For MP cows with low plasma Ca, BOL decreased risk of additional Ca treatment (≤1.8 mmol/L; RR = 0.57, 95% CI = 0.40 to 0.80) as well as risk of one or more health disorders (≤2.15 mmol/L; RR = 0.90, 95% CI = 0.85 to 0.95). Supplementation with a single oral dose of Ca could be targeted to periparturient risk groups for improved health. Calcium status did not differentiate responses of PP cows, but MP cows with low Ca at parturition had improved health status when supplemented.

Association of immediate postpartum plasma calcium concentration with early-lactation clinical diseases, culling, reproduction, and milk production in Holstein cows.

The objective of this study was to evaluate the association of postpartum plasma Ca concentration with early-lactation disease outcomes, culling within 60 d in milk, pregnancy to first service, and milk production. A total of 1,453 cows from 5 commercial dairy farms in New York State were enrolled in a prospective cohort study from February to November 2015. Blood samples were collected within 12 h of parturition, and plasma was submitted to a diagnostic laboratory for total Ca measurement. Early-lactation disease, reproductive performance, and milk production from Dairy Herd Improvement Association (DHIA) test-day data were compiled from each farm's management software. Multivariable Poisson regression models were built to evaluate the association of plasma Ca with the risks of retained placenta (RP), metritis, displaced abomasum (DA), clinical mastitis, culling within 60 d in milk, and pregnancy to first service. Repeated-measures ANOVA were used to evaluate the association of Ca at parturition with milk production across the first 9 DHIA tests. Herd was considered a random effect in all models. Primiparous cows were modeled separately from multiparous cows if differential responses were observed. Calcium was not associated with the risk of RP, metritis, clinical mastitis, or pregnancy to first service in primiparous or multiparous cows. For multiparous cows only, higher Ca concentration tended to be associated with increased culling within the first 60 d in milk. Multiparous cows with Ca ≤1.85 mmol/L had an increased risk of being diagnosed with a DA compared with cows with Ca >1.85 mmol/L. For the milk production models, Ca was not associated with the amount of milk produced within the first 9 DHIA tests in primiparous cows; however, multiparous cows with Ca ≤1.95 mmol/L produced, on average, 1.1 kg more milk per day across the 9 DHIA tests than their multiparous counterparts with Ca >1.95 mmol/L. Our results indicate that plasma Ca concentration measured within 12 h of parturition is a poor predictor of early-lactation health outcomes. Reduced Ca concentration in the immediate postpartum period was associated with higher milk production in multiparous cows. From these results, we caution that studies attempting to categorize subclinical hypocalcemia based on a single sample in the immediate postpartum period could misclassify the disorder.