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OBJECTIVE: To estimate the number of people alive in England & Wales who have lost a close family member in a fatal road traffic crash. DESIGN: Linkage of mortality records in a sample of 1.1% of the population during 1971-2005 with records from the 1971, 1981, 1991 and 2001 censuses. For each person killed in a road traffic crash, the number of close family members still alive in 2005 was estimated by applying life table probabilities of survival. SETTING: England & Wales, UK. SUBJECTS: Adults and children killed in road traffic crashes 1971-2005. MAIN OUTCOME MEASURE: Number of close family members alive in 2005. RESULTS: In a sample of approximately 1.1% of the population in 1971-2005, a total of 1801 adults and children died in road traffic crashes. These deaths left 6467 close family members bereaved in 2005, corresponding to a total of 590 518 bereaved in the population (including 131 399 parents who had lost a child and 107 384 offspring who had lost a parent). CONCLUSION: Over 1% of the population of England & Wales alive in 2005 had lost a close family member in a fatal road traffic crash since 1971. This may imply a greater public health burden of road traffic crashes than previously estimated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to determine whether combinations of characteristics, abstracted from drawings of elders made by middle school students, grouped together to form cohesive perceptions, or stereotypes, of human aging. METHODS: We abstracted 49 characteristics from drawings of elders made by 1,944 students at two middle schools in San Antonio, Texas, at the beginning of the 1998-1999 school year. Correlational and factor analyses were used to determine if there was an underlying structure or grouping to the characteristics. Logistic regression was used to determine the variables associated with the investigators' classification of the images as positive, neutral, or negative. RESULT: The standardized alpha coefficient for the 49 variables was low (alpha = 0.37). The Spearman rho correlations between the variables were also low, with 90.2% of the 1,176 comparisons being < 0.10. Exploratory factor analyses did not provide a useful grouping of characteristics drawn by the students, including analyses stratified by gender and restricted to the most common 34 characteristics. Among the 49 characteristics that emerged from the drawings, 11, 4, and 11 traits were directly associated with classifying the drawings as positive, neutral, or negative, respectively. DISCUSSION: These analyses indicate that middle school students have not formed strong images regarding aging: No clear cohesive stereotypes of elders emerged from the images drawn by these children. Absence of stereotypic views implies that middle school students may not have a built-in bias toward older people and age-associated changes. This suggests that young adolescents are at a point where instruction including gerontological content can be used to effectively teach about aging and health promotion. [ABSTRACT FROM AUTHOR]

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Background: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined., Methods: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis., Results: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01., Conclusion: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460., Funding: Defense Health Agency and others., Competing Interests: Conflict of Interest Statement TG-Paid consultant and employee of Fenwal, a Fresenius Kabi company; AC-Scientific Advisory Board of Sabtherapeutics (cow-derived human immunoglobulins COVID-19 treatment and other infectious diseases) and Ortho Diagnostics Speakers Bureau; MAH-contracts from Gilead Sciences, Insmed, AN2 Therapeutics, AstraZeneca to the University of Cincinnati, outside the submitted work. EB-member of the FDA Blood Products Advisory Committee; SS reports research grants; F2G, Cidara, Ansun, Zeteo: personal fees as consultant, advisory board, data safety monitoring board member; Celltrion, Adagio, Immunome, Karius, Pfizer, Scynexis, Adamis, Karyopharm, Intermountain Health: Stock options: Immunome; CS: Centers for Disease Control and Prevention, Merck, Pfizer: Research Grants. All other authors report no relevant disclosures.

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials., Study Design and Methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders., Results: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications., Discussion: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Artificial insemination using semen from genetically superior sires remains one of the most effective biotechnologies ever commercialized for animal breeding purposes. Genetic progress, however, cannot begin until conception occurs. Processing laboratories that provide cryopreserved bull semen for commercial use depend on in vitro assays of semen quality to identify samples that are expected to result in less than desirable conception rates. These identified samples are discarded, rather than released to salable inventories, with the desired effect of minimizing variance in field fertility among both sires and individual collections. Although the industry was successfully founded on subjective assessment of motility and acrosome integrity, flow cytometric and computer-assisted sperm analysis offer more objective and repeatable measures of sperm quality attributes. Albeit more expensive to implement, the increased precision and repeatability when using these objective assays lends to greater confidence in the accuracy of decisions for individual collections and (or) bulls. The efficacy of a quality control program is evidenced by the range in sire fertility estimates calculated from field fertility data, which have historically indicated >90% of all sires achieve fertility deviation within ±3% points of the breed average. This impressive precedent implies somewhat limited opportunity for transition to objective assessments to have a meaningful impact on an already narrow range of fertility distributions. Nonetheless, flow cytometric assessments of novel attributes of sperm quality hold promise for detection of truly sub-fertile sires (deviations < -3) that presently elude detection with use of existing semen bioassays., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain., Methods: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion., Results: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized., Conclusions: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain., Methods: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021., Results: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions., Conclusion: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic., Trial Registration: ClinicalTrials.gov number, NCT04373460.

Background: In 2019, the United States Food and Drug Administration published its final recommendations to mitigate bacterial contamination of platelets. We sought to evaluate our secondary bacterial culture (SBC) strategy in light of those recommendations., Study Design and Methods: A retrospective analysis was conducted of SBC data (October 2016-2019) at our institution. SBC was performed upon receipt (Day 3 after collection); 5 mL of platelet product was inoculated aseptically into an aerobic bottle and incubated at 35°C for 3 days. For 8 months, a 10-mL inoculum was trialed. No quarantine was applied. All positive cultures underwent Gram staining and repeat culture of the platelet product (if available). A probable true positive was defined as concordant positive culture between the initial and repeat culture. The incidence of probable true- and false-positive cultures were reported descriptively and differences evaluated by sampling volume., Results: Over 3 years, 55 896 platelet products underwent SBC, yielding 30 initial positive results (approx. 1/1863 platelets); 25 (83.3%) signaled within 24 hours of SBC. The rates of probable true positive, false positive, and indeterminate for 5 mL were 0.027% (1/3771), 0.002% (1/45 251) and 0.018% (1/5656), respectively. The respective rates for 10 mL were 0.018% (1/5323), 0.07% (1/1521), and 0%. Seven of eight (87.5%) false-positive SBCs occurred with a 10-mL inoculum. No septic transfusion reactions were reported., Conclusion: SBC continues to interdict bacterially contaminated units of platelets. Our findings suggest higher rates of false positivity using large-volume inocula., (© 2020 AABB.)

Background: Bacterial contamination of platelets remains the leading infectious risk from blood transfusion. Pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC) have been proposed as alternative risk control strategies, but a comprehensive financial comparison has not been conducted., Study Design and Methods: A Markov-based decision tree was constructed to model the financial and clinical impact of PR, PORt, and SBC, as well as a baseline strategy involving routine testing only. Hospitals were assumed to acquire leukoreduced apheresis platelets on Day 3 after collection, and, in the base case analysis, expiration would occur at the end of Day 5 (PR and SBC) or 7 (PORt). Monte Carlo simulations assessed the direct medical costs for platelet acquisition, testing, transfusion, and possible complications. Input parameters, including test sensitivity and specificity, were drawn from existing literature, and costs (2018 US dollars) were based on a hospital perspective., Results: The total costs per unit acquired by the hospital under the baseline strategy, PR, PORt, and SBC were $651.45, $827.82, $686.33, and $668.50, respectively. All risk-reduction strategies decreased septic transfusion reactions and associated expenses, with the greatest reductions from PR. PR would add $191.09 in per-unit acquisition costs, whereas PORt and SBC would increase per-unit testing costs by $31.79 and $17.26, respectively. Financial outcomes were sensitive to platelet dating; allowing 7-day storage with SBC would lead to a cost savings of $12.41 per transfused unit. Results remained robust in probabilistic sensitivity analyses., Conclusions: All three strategies are viable approaches to reducing bacterially contaminated platelet transfusions, although SBC is likely to be the cheapest overall., (© 2019 AABB.)

Background: Bacterial contamination and associated septic transfusion reactions (STRs) remain the leading infectious risk to the blood supply. We sought to characterize the risk and clinical presentation of blood culture-positive transfusion reactions (BCPTRs) and STRs at our institution., Study Design and Methods: A retrospective analysis was conducted of all suspected transfusion reactions reported to the transfusion service at a 1000-bed tertiary academic medical center from January 2009 to September 2016. Routine investigation included review of the clinical presentation, Gram stain, and bacterial culture of residual blood from the transfused product or associated blood bag. BCPTRs were defined by the presence of a positive bacterial culture in the blood product and/or recipient. STRs met definitive Centers for Disease Control and Prevention hemovigilance criteria for transfusion-transmitted infection, with definite imputability and concordant bacterial culture of the blood product and recipient., Results: A total of 688,514 blood products were transfused during the study period, 3170 transfusion reactions were reported, and 18 (0.57%) were BCPTRs of which seven (0.22%) were STRs. Fifteen of 18 (83.3%) BCPTRs and six of seven (85.7%) were associated with transfusion of apheresis platelets. Major symptoms and signs of BCPTRs included chills (67%), fever (61%), and nausea and vomiting (50%). Four of seven (57.1%) STRs were classified as severe or life-threatening., Conclusion: BCPTRs are rare yet potentially serious. The signs and symptoms of BCPTRs, and associated STRs, are not specific, posing risk of misclassification. Challenges surrounding reporting and case ascertainment underscore the need for laboratory measures to address residual risk of contamination., (© 2018 AABB.)

Background: Bacterial contamination of platelets remains a major transfusion-associated risk despite long-standing safety measures in the United States. We evaluated an approach using secondary bacterial culture (SBC) to contend with residual risk of bacterial contamination., Study Design and Methods: Phased implementation of SBC was initiated in October 2016 for platelets (all apheresis collected) received at our institution from the blood donor center (Day 3 post collection). Platelet products were sampled aseptically (5 mL inoculated into an aerobic bottle [BacT/ALERT BPA, BioMerieux, Inc.]) by the blood bank staff upon receipt, using a sterile connection device and sampling kit. The platelet sample was inoculated into an aerobic blood culture bottle and incubated at 35°C for 3 days. The cost of SBC was calculated on the basis of consumables and labor costs at time of implementation., Results: In the 13 months following implementation (October 6, 2016, to November 30, 2017), 23,044/24,653 (93.47%) platelet products underwent SBC. A total of eight positive cultures were detected (incidence 1 in 2881 platelet products), seven of which were positive within 24 hours of SBC. Coagulase negative Staphyloccus spp. were identified in four cases. Five of the eight cases were probable true positive (repeat reactive) and interdicted (cost per averted case was US$77,935). The remaining three cases were indeterminate. No septic transfusion reactions were reported during the observation period., Conclusion: We demonstrate the feasibility of SBC of apheresis platelets to mitigate bacterial risk. SBC is lower cost than alternative measures (e.g., pathogen reduction and point-of-release testing) and can be integrated into workflow at hospital transfusion services., (© 2018 AABB.)

Background: Hospital-wide massive transfusion protocols (MTPs) primarily designed for trauma patients may lead to excess blood products being prepared for nontrauma patients. This study characterized blood product utilization among distinct trauma and nontrauma MTPs at a large, urban academic medical center., Methods: A retrospective study of blood product utilization was conducted in patients who required an MTP activation between January 2011 and December 2015 at an urban academic medical center. Trauma MTP containers included 6 red blood cell (RBC) units, 5 plasma units, and 1 unit of apheresis platelets. Nontrauma MTP containers included 6 RBC and 3 plasma units., Results: There were 334 trauma MTP activations, 233 nontrauma MTP activations, and 77 nontrauma MTP activations that subsequently switched to a trauma MTP ("switched activations"). All nontrauma MTP activations were among bleeding patients who did not have a traumatic injury (100% [233/233]). Few patients with a nontrauma activation required ad hoc transfusion of RBC units (1.3% [95% confidence interval {CI}, 0.3%-3.7%]) or plasma (3.4% [95% CI, 1.5%-6.7%]), and only 45.5% (95% CI, 39.0%-52.1%) required ad hoc transfusion of apheresis platelets. Compared to trauma and switched activations, nontrauma activations transfused a lower median number of RBC, plasma, and apheresis platelet units (P < .001 for all comparisons). There was also a lower median number of prepared but unused plasma units for nontrauma activations (3; [interquartile range {IQR}, 3-5]) compared to trauma (7; [IQR, 5-10]; P < .001) and switched activations (8; [IQR, 5-11]; P < .001). The median number of unused apheresis platelet units was 1 (IQR, 1-2) for trauma activations and 0 (IQR, 0-1) for switched activations. There was a high proportion of trauma and switched activations in which all of the prepared apheresis platelet units were unused (28.1% [95% CI, 23.4%-33.3%] and 9.1% [95% CI, 3.7%-17.8%], respectively)., Conclusions: The majority of initial nontrauma MTP activations did not require a switch to a trauma MTP. Patients remaining under a nontrauma MTP activation were associated with a lower number of transfused and unused plasma and apheresis platelet units. Future studies evaluating the use of hospital-wide nontrauma MTPs are warranted since an MTP designed for nontrauma patient populations may yield a key strategy to optimize blood product utilization in comparison to a universal MTP for both trauma and nontrauma patients.

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG.

Despite the importance of skeletal growth during adolescence, there is limited research reporting vitamin D status and its predictors in adolescents. Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin D (25(OH)D) concentrations in adolescents. Serum 25(OH)D concentrations were measured in the same participants at 14 and 17 years (n 1045 at both time points). The percentage of adolescents with serum 25(OH)D concentrations < 50, 50-74·9 and ≥ 75 nmol/l was reported year-round and by month of blood collection. We examined the predictors of serum 25(OH)D concentrations, including sex, race, month of blood collection, physical activity, BMI, family income, and Ca and vitamin D intakes (n 919 at 14 years; n 570 at 17 years), using a general linear mixed model. At 14 years, 31 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and a further 4 % had concentrations < 50 nmol/l. At 17 years, 40 % of adolescents had serum 25(OH)D concentrations between 50 and 74·9 nmol/l and 12 % had concentrations < 50 nmol/l. Caucasian ethnicity, being sampled at the end of summer, exercising more, having a lower BMI, a higher Ca intake and a higher family income were significantly associated with higher serum 25(OH)D concentrations. The proportion of adolescents with serum 25(OH)D concentrations < 50 nmol/l was low in this Western Australian cohort. There is a need for international consensus on defining adequate vitamin D status in order to determine whether strategies to increase vitamin D status in adolescents are warranted.

Background: Recent transcriptomic analysis of the bovine Y chromosome revealed at least six multi-copy protein coding gene families, including TSPY, HSFY and ZNF280BY, on the male-specific region (MSY). Previous studies indicated that the copy number variations (CNVs) of the human and bovine TSPY were associated with male fertility in men and cattle. However, the relationship between CNVs of the bovine Y-linked HSFY and ZNF280BY gene families and bull fertility has not been investigated., Results: We investigated the copy number (CN) of the bovine HSFY and ZNF280BY in a total of 460 bulls from 15 breeds using a quantitative PCR approach. We observed CNVs for both gene families within and between cattle breeds. The median copy number (MCN) of HSFY among all bulls was 197, ranging from 21 to 308. The MCN of ZNF280BY was 236, varying from 28 to 380. Furthermore, bulls in the Bos taurus (BTA) lineage had a significantly higher MCN (202) of HSFY than bulls in the Bos indicus (BIN) lineage (178), while taurine bulls had a significantly lower MCN (231) of ZNF280BY than indicine bulls (284). In addition, the CN of ZNF280BY was positively correlated to that of HSFY on the BTAY. Association analysis revealed that the CNVs of both HSFY and ZNF280BY were correlated negatively with testis size, while positively with sire conception rate., Conclusion: The bovine HSFY and ZNF280BY gene families have extensively expanded on the Y chromosome during evolution. The CN of both gene families varies significantly among individuals and cattle breeds. These variations were associated with testis size and bull fertility in Holstein, suggesting that the CNVs of HSFY and ZNF280BY may serve as valuable makers for male fertility selection in cattle.

Multi-copy gene families are especially prevalent in the male-specific region (MSY) of the mammalian Y chromosome. Copy number variations (CNV) of these Y-linked gene families have been shown to affect human and animal fertility. The PRAMEY (Preferentially expressed antigen in melanoma, Y-linked) gene family is a newly identified, bovid-specific Y-linked gene family, which codes for a cancer/testis antigen that is expressed predominantly in testis and various tumors. The PRAMEY gene family is believed to play an important role in spermatogenesis and male fertility in cattle. The objective of this study was to investigate the CNV of PRAMEY within and across breeds and to determine whether CNV was associated with reproductive traits in Holstein bulls. A quantitative real-time PCR method was applied to measure the copy number of PRAMEY among 460 bulls using a Y-linked single copy gene, DDX3Y (DEAD box polypeptide 3, Y-linked), as a reference. The median copy number of PRAMEY was 13, ranging from 2 to 31. Significant variations in PRAMEY copy number were observed among 15 breeds investigated. Holstein bulls had the lowest median copy number (12), whereas Limousin bulls possessed the highest median copy number (26). Furthermore, bulls in the taurine lineage (13) had a significantly lower median copy number than those bulls in the indicine lineage (20). Association analysis revealed that PRAMEY copy number was correlated negatively with scrotal circumference (SC), relative scrotal circumference (RLSC), percentage of normal sperm (PNS), and nonreturn rate (NRR), but had no significant association with postthaw motility (PTM), incubated motility (IM), percentage of intact acrosome (PIA), sire conception rate (SCR), or relative breeding efficiency (RBE). The data from this study indicate that CNV of the PRAMEY gene family is associated with male reproductive traits and may serve as a valuable marker for sire fertility selection at an early age in cattle., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Teenage motherhood is relatively common in the UK, but little is known about related health inequalities in this population. We estimated cause-specific mortality risks over three decades in a nationally representative cohort., Method: We examined premature mortality in a 1.1% sample of all women who were teenagers in England and Wales during the 1970s, 1980s and 1990s using data from the Office for National Statistics Longitudinal Study (ONS LS). Our primary outcome was suicide. Long-term follow-up to 31 December 2006, to a potential maximum age of 49 years, was achieved through near-complete routine linkage to national mortality records. We created a time-dependent exposure variable, with relative risks estimated according to age when women first experienced motherhood versus a reference group of those currently without children., Results: Women who were teenage mothers were around 30% more likely to die prematurely by any cause and almost 60% more likely to die unnaturally, whereas first-time motherhood at mature age conferred lower risk compared to women without children. Teenage motherhood was associated with a more than doubled risk of suicide [mortality rate ratio (MRR) 2.23, 95% confidence interval (CI) 1.30-3.83], and elevated risks of fatal cancer of the cervix and lung were also found. Changing the reference category to first-time mothers at 20 years and above also revealed a significant elevation in risk of accidental death., Conclusions: The complex psychosocial needs of these women require greater attention from clinicians, public health professionals, social services and policymakers. Their elevated risk of poor health outcomes may persist well beyond the actual teenage motherhood years.

The conception rates of Holstein heifers after AI with 2.1 or 10 × 10(6) sperm dosages of sex-sorted or conventionally processed sperm were compared. Ejaculates collected by artificial vagina from 8 Holstein sires were cryopreserved at either 2.1 or 10 × 10(6) sperm per dose with or without sorting to 90% purity for X-chromosome-bearing spermatozoa using flow cytometry. All treatments were processed in an egg-yolk (20%), TRIS, glycerol (7%) extender and packaged in color-coded 0.25-mL French straws. Straws (n=350 straws/treatment per sire) were packaged and distributed in aliquots of 12 (3 straws of each treatment) to 51 herds of Holstein heifers. Straw color was recorded in the on-farm record keeping system at the time of AI and retrieved by electronic download. In total, 9,172 services were recovered, providing a mean sample size of 287±3.5 services/sperm dose per semen type within sire (range: 248 to 318). Conception rates were influenced by the main effects of herd, sire, semen type, sperm dosage, and service number. The herd by sperm dosage interaction was the only interaction determined to be significant and implies that some herds (technicians) are more proficient than others at maintaining high levels of conception with decreased sperm dosages. Across herds and sires, the conception rates of each semen type by sperm dosage combination were as follows: 2.1 × 10(6) sex-sorted, 38%, n=2,319; 10 × 10(6) sex-sorted, 44%, n=2,279; 2.1 × 10(6) conventional, 55%, n=2,282; and 10 × 10(6) conventional, 60%, n=2,292. The observation that conception rates of sex-sorted semen were improved by the 10 × 10(6) sperm dosage is encouraging toward the prospectus of development of a commercially available sex-sorted product with improved conception potential over existing technology. However, the failure of the 10 × 10(6) sex-sorted sperm dosage to achieve conception rates comparable to either dosage of conventional semen is somewhat discouraging toward the plausibility of comparable conception rates to conventional semen in the absence of major technological advances in efficiency of sperm sorting or cryopreservation., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective was to compare conceptions rates of Holstein cows and heifers after artificial insemination (AI) with 2.1 or 3.5x10(6) sex-sorted sperm or 15x10(6) conventional sperm. Ejaculates collected from 7 Holstein sires were cryopreserved conventionally at 15x10(6) sperm per dose or sorted to 90% purity for X-chromosome-bearing spermatozoa using flow cytometry and cryopreserved at either 2.1 or 3.5x10(6) sperm per dose. All treatments were processed in an egg-yolk (20%), Tris, glycerol (7%) extender and packaged in color-coded 0.25-mL French straws. Straws (n=700 straws/dosage per sire) were packaged and distributed in aliquots of 12 (4 straws/sperm dosage) to 69 Holstein herds with an across-herd goal of achieving approximately 50% use in heifers and cows. Straw color was recorded in the on-farm recordkeeping system at the time of AI and retrieved by electronic download. Data for cows and heifers were analyzed separately. Among heifers, 6,268 services were retrieved from 45 herds (298+/-4.2 services/sperm dose per sire; range: 244 to 344). Conception rate of heifers was influenced by the sire by treatment interaction. Conception rate of the 2.1 and 3.5x10(6) sex-sorted sperm dosages were comparable in 6 of 7 sires. Conception rate of both sex-sorted dosages were less than those of conventional semen for 6 of 7 sires. Across sires, heifer conception rates for 2.1 and 3.5x10(6) sex-sorted sperm dosages and 15x10(6) conventional dosages were 44, 46, and 61%, respectively. Among cows, 5,466 services were retrieved from 52 herds (260+/-3.3 services/sperm dose per sire; range: 236 to 289). Conception rates of cows were influenced by herd, sire, and sperm dosage. Conception rates of the 2.1 and 3.5x10(6) sex-sorted sperm dosage were comparable for all 7 sires. Conception rates of 2.1x10(6) sex-sorted sperm dosage were less than those of conventional semen for 4 of 7 sires and conception rates of the 3.5x10(6) sex-sorted sperm dosage were less than those of conventional semen for 2 of 7 sires. Across sires, conception rates for 2.1 and 3.5x10(6) sex-sorted sperm dosages and 15x10(6) conventional dosages in cows were 23, 25, and 32%, respectively. In conclusion, these data could not confirm that a meaningful improvement in conception rates should be expected in cows or heifers from increasing sex-sorted sperm dosage from 2.1 to 3.5x10(6) sperm per dose., (Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Red blood cell (RBC) product wastage in hospitals is reported to range from 0.1% to 6.7%. Wastage at our institution averaged 4.4% of 63,000 issued RBC products. Data indicated that approximately 87% of wasted RBC units were either individual units that were out of blood bank for more than 30 minutes (dispensed but not administered) or units packed in transport containers that had temperature indicators affixed to each unit. We hypothesized that Lean Sigma methodology could be used to reduce RBC wastage by 50%., Study Design and Methods: An interdisciplinary hospital team (transfusion medicine, nursing, and anesthesiology) used Lean Sigma methodology as a tool to reduce RBC product wastage, with a focus on container wastage, which was determined to yield the largest impact. Using the five-part Lean Sigma process-define, measure, analyze, improve, and control-the team collected baseline wastage data, identified major factors affecting RBC product wastage, and implemented interventions to reduce amount of wastage., Results: Factors identified as contributors to RBC wastage most amenable to improvement were lack of awareness and training of staff ordering and handling RBC products, management of temperature-validated containers, inconsistent interpretation of RBC temperature indicators, and need for accountability when ordering blood products. Overall RBC product wastage decreased from 4.4% to a sustained rate of less than 2%. This reduction decreased the number of RBC units wasted by approximately 4300 per year, savings approximately $800,000 over the 4-year period of the study., Conclusions: Lean Sigma methodology was an effective tool for reducing RBC wastage in a large academic hospital., (© 2010 American Association of Blood Banks.)

These data summarize on-farm records of dairy herds (n=211) using sexed semen. Sexed semen was predominantly used at first and second service in virgin heifers, which is reflected in younger ages at AI and at calving. Conception rates at first service averaged 47% for Holstein heifers and 53% for Jersey heifers, which were approximately 80% of that achieved with conventional semen. Analysis of inter-estrus intervals provides no evidence that cycle lengths are extended by use of sexed semen. Among singleton births, 89% were reported as female offspring and this rises to 90% for gestation lengths within a normal 265-295 d range. Age at calving appeared to interact with calf sex and semen type to influence the incidence of stillbirths. Semen type had no effect on the incidence of stillbirths among heifers delivering female calves. However, the incidence of stillbirths among heifers delivering male calves was greater for those conceived from sexed semen and was only partially explained by age at calving. Because the incidence of male calves from sexed semen is only 10%, the total incidence of stillbirths was not affected by semen type. In conclusion, failure to differentiate sexed from conventional semen in data recording and preferential bias in use of sexed semen in younger, more fertile females makes legitimate comparisons of sexed and conventional semen in the commercial setting difficult. When used in Holstein heifers, the average first service conception rate achieved with sex-sorted semen was 47%, which appeared to approximately 80% of that achieved with conventional semen in the same herds. The percentage of female calves (89%) was consistent with expectations. After adjusting for age at calving, sexed semen had no affect on the total incidence of stillbirths, however the source for an apparent increased incidence of stillbirth among male calves born from X-sorted sperm populations requires further investigation.

Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 x 10(6) sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 +/- 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire x sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 x 10(6) (59.5%) than for the 2.1 x 10(6) (46.4%) sperm dose and intermediate for the 3.5 x 10(6) sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 +/- 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are warranted to determine whether and how such a practice can be implemented cost effectively for the benefit of the dairy industry.

A survey was mailed to approximately 4,000 herds participating in a young sire progeny test program to estimate the percentage of herds that selectively alter the voluntary waiting period (VWP) for individual cows or groups of cows. Responses were received from 673 herds (17%; 583 Holsteins, 55 Jerseys, 35 other dairy breeds). The mean VWP cited by respondents was 56 +/- 0.6 d (range = 30 to 90 d) and did not differ by breed. Among responding herds, 64% (432/673) indicated the VWP was selectively altered for one or more reasons. The most frequently cited reasons for altering the VWP were postpartum health (50%), season (18%), milk yield (18%), parity (14%), and other reasons (14%). In Holstein herds that altered the VWP based on milk yield, the highest production group averaged 14 more days to first service than the lowest production group (> or =40 vs. <20 kg of energy-corrected milk, respectively). In contrast, days to first service were nearly identical for all production groups in Holstein herds that did not vary the VWP based on milk yield. In conclusion, management decisions to selectively alter the VWP led to differences in days to first service and may have a confounding effect on genetic estimates of daughter fertility. Opportunities to improve the accuracy of daughter pregnancy rate estimates may reside in models that adjust for VWP management decisions on a within-herd basis.

Our ability to use human embryonic stem (hES) cells in cell replacement therapy for Parkinson's disease depends on the discovery of ways to simply and reliably differentiate a dopaminergic (DA) phenotype in these cells. Although several protocols exist for the differentiation of DA traits in hES, they involve the prolonged use of complex media with undefined components, cell conditioned media and/or co-culture with various cells, usually of animal origin. In this study, several well-characterized (H9, BG01) and several new uncharacterized (HUES7, HUES8) hES cell lines were studied for their capacity to differentiate into DA neurons in culture using a novel rapid protocol which uses only chemically-defined human-derived media additives and substrata. Within 3 weeks, cells from all 4 cell lines progressed from the undifferentiated state to beta-tubulin III positive cells expressing DA markers in vitro. Moreover, transplantation of these cells into the striata of 6-hydroxydopamine-treated rats at the neuronal progenitor stage resulted in the appearance of differentiated DA traits in vivo 2-3 weeks later.

Cell replacement therapy in Parkinson's disease depends on a reliable source of purified dopamine (DA) neurons (PDN) and the identification of factors relevant to their survival. Our goal was to genetically tag and purify by flow cytometry embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of human tyrosine hydroxylase promoter driving expression of the enhanced green fluorescent protein(GFP) for studies in vivo and in vitro. A 99% purification of GFP+ cells was achieved. When transplanted into 6-hydroxydopamine-treated rat striatum, PDN survived, became well-integrated and produced recovery from amphetamine-induced motor behaviors. However, when grown in culture, PDN died within days of plating. No known growth factors prevented PDN death as did incubation with novel factors in glia/glial-conditioned media. We conclude that GFP-tagged DA neurons can be purified to homogeneity and can survive and function when grown with glial factors in vitro or after transplantation in vivo.

Influence of interactions of straw-thawing method with sire and extender type (milk or egg yolk-based) on postthaw sperm motility and conception rates of dairy cows was assessed. In experiment 1, sperm from 10 Holstein sires were frozen in egg yolk citrate and heated whole-milk extenders using a split-ejaculate technique. Straws were thawed in a 37 degrees C water bath with or without 3 min of exposure to a 37 degrees C warming plate while wrapped in a paper towel (air-thaw). Percentage of motile sperm was assessed after 1 min and 3 h of incubation at 37 degrees C. In experiment 2, sperm from 3 Holstein sires were frozen in egg-yolk citrate and a nonheated whole milk extender using a split-ejaculate technique. Straws were thawed and motility was assessed as in experiment 1. Conception rates (n = 475) were compared in a single herd of Holstein cows after thawing straws in 35 degrees C water for 45 s or after air-thawing by wiping straws with a paper towel upon removal from the storage vessel and placing directly into the insemination gun. In each experiment, interactions between thaw method and sire, extender type, or both, indicated that conditions may be created that facilitate sperm tolerance of air-thaw procedures. When a significant thaw method effect was detected in either experiment, air-thaw was consistently associated with the lesser measure of sperm motility, conception, or both. In conclusion, although some sire x extender combinations seem to be tolerant of air-thaw procedures, other combinations are more sensitive, resulting in reduced postthaw sperm survival, conception rates of cows, or both, in response to air-thaw.

In September 2004, linked data from the 2001 Census was made available in the Office for National Statistics (ONS) Longitudinal Study (a 1 per cent sample of the population of England and Wales). The study now includes information from four censuses on sample members and the people they lived with. The availability of this new information, the length of follow-up and other features of the study (such as records of births and deaths to sample members) provide new opportunities for analysing change--both over the life course, between time periods, and between generations. This article illustrates the potential for analysis of continuity and change with new results on intergenerational social mobility, and on parental social class and age at first birth.

The efficacy of various combinations of melengestrol acetate (MGA), GnRH, and PGF2alpha for the synchronization of estrus in Angus-based beef cattle was compared. Hormones were administered as follows: MGA, 0.5 mg x animal(-1) x d(-1) mixed in a grain carrier; GnRH, 100 microg i.m.; PGF2alpha, 25 mg i.m. In Exp. 1, 2, and 3, cows were randomly assigned to treatments by parity and interval postpartum. The detection of estrus and AI were conducted from d -2 until 72 to 96 h after PGF2alpha, at which time cows not detected to be in estrus received GnRH and fixed-time AI (TAI). Data were analyzed separately for primiparous and multiparous cows. In Exp. 1, cows (n = 799) at three locations received GnRH on d -7 and PGF2alpha on d 0 and either no further treatment (GnRH-PGF) or short-term MGA from d -6 through d -1 (STMGA). Among multiparous cows, conception rate at TAI was greater (P < 0.05) for STMGA (41%, 47/115) than for GnRH-PGF treated cows (26%, 24/92). Across herds and parity, synchronized AI pregnancy rate (SPR) was not affected (P > 0.10) by treatment (GnRH-PGF vs. STMGA; 54%, 210/389 vs. 57%, 228/402). In Exp. 2, cows (n = 484) at three locations received either STMGA or long-term MGA from d -32 through d -19, GnRH on d -7, and PGF2alpha on d 0 (LTMGA). Among primiparous cows, SPR was greater (P < 0.01) in LTMGA (65%, 55/85) than STMGA-treated cows (46%, 40/87). Treatment had no effect (P > 0.10) on SPR among multiparous cows (STMGA vs. LTMGA; 59%, 92/155 vs. 64%, 101/157). In Exp. 3, cows (n = 838) at four locations received the LTMGA treatment and either no further treatment or an additional period of MGA exposure from d -6 through d -1 (L&STMGA). Among primiparous cows, SPR tended to be influenced (P < 0.10) by the herd x treatment interaction and was greater (P < 0.01) among L&STMGA (86%, 19/22) than LTMGA-treated cows (56%, 14/25) at a single location. Among multiparous cows, SPR was lower (P < 0.05) in L&STMGA (46%, 165/358) than LTMGA-treated cows (55%, 184/336). In Exp. 4, Angus heifers (n = 155) received either STMGA or 14 d of MGA (d -32 through d -19) and PGF2alpha on d 0 (MGA-PGF). The detection of estrus and AI were conducted from d -2 to d 6. Interval to estrus was greater (P < 0.05) and estrous response was lower (P < 0.05) in STMGA than MGA-PGF-treated heifers. In conclusion, primiparous cows responded more favorably to longer-duration MGA treatments than did multiparous cows. All protocols achieved sufficient SPR to justify their use for improved reproductive management of postpartum beef cows.

The development of cell replacement therapies for the treatment of neurodegenerative disorders such as Parkinson's disease (PD) may depend upon the successful differentiation of human neural stem/progenitor cells into dopamine (DA) neurons. We show here that primary human neural progenitors (HNPs) can be expanded and maintained in culture both as neurospheres (NSPs) and attached monolayers where they develop into neurons and glia. When transplanted into the 6-hydroxydopamine-lesioned rat striatum, undifferentiated NSPs survive longer (60% graft survival at 8-16 weeks vs. 30% graft survival at 8-13 weeks) and migrate farther than their attached counterparts. While both NSP and attached cells continue to express neuronal traits after transplantation, the spontaneous expression of differentiated transmitter-related traits is not observed in either cell type. However, following predifferentiation in culture using a previously described cocktail of reagents, approximately 25% of HNPs can permanently express the DA enzyme tyrosine hydroxylase (TH), even following replating and removal of the DA differentiation cocktail. When these predifferentiated HNPs are transplanted into the brain, however, TH staining is not observed, either because expression is lost or TH-expressing cells preferentially die. Consistent with the latter view is a decrease in total cell survival and migration, and an enhanced glial response in these grafts. In contrast, we found that the overall survival of HNPs is improved when cells engraft near blood vessels or CSF compartments or when they are placed into an intact unlesioned brain, suggesting that there are factors, as yet unidentified, that can better support the development of engrafted HNPs.

Purpose: Sentence completion exercises require students to give open-ended responses to prompts. The first purpose of this article is to describe the method of sentence completion to assess middle-school children's attitudes and beliefs about aging. The second purpose is to describe the patterns of characteristics that children associate with aging., Design and Methods: Two middle schools in San Antonio, TX agreed to have their students participate in the sentence completion exercises at the beginning of the 1998-1999 school year. Teachers asked students to write responses to the following prompts: "Old is.," "You know you are old when.," "You know your parents are old when.," "When I am old, I.," and "Old people." We coded the responses for their characteristics and whether they were positive, negative, or neutral., Results: Of the 2,476 students, 1,874 (75.6%) wrote responses to at least one prompt. Overall, we collected 3,700 responses and coded 9,438 characteristics (2.6 characteristics per response). The most common characteristics of aging were having wrinkles (21.1%), having gray hair or being bald (20.0%), and being less active (17.5%). Students had a much more positive view of their future (55.4%) compared with their view of aging elicited by the other prompts (range of 4.9-25.7% positive responses). Students infrequently associated old age with specific conditions; only 4.6% mentioned diseases, 6.0% mentioned being ill or taking medications, and 5.7% mentioned sensory problems., Implications: Middle-school students view their futures much more positively than the changes they observe in their parents and other elders. Students infrequently identified specific diseases or impairments as responsible for the changes they observe with aging. These observed responses provide a starting point for educators to develop and deliver gerontologically based materials that teach about healthful habits to maintain independence across a life span.

In Experiment 1, the effects of two pre-synchronization treatments on synchronized AI pregnancy rates of lactating dairy cattle were compared. Lactating Holstein cows (n=159) received 100 microg of GnRH (im) on day -7 and 25mg of PGF(2alpha) (im) on day 0 and were observed once daily for signs of estrus from day -3 to day 3. Cows detected in standing estrus and those that had lost significant amounts of tail-chalk in the previous 24h were immediately inseminated in a once-daily observation/AI program. Cows not detected in estrus by 72 h after PGF(2alpha) received fixed-time AI (TAI) and a concurrent 100 microg injection of GnRH (im). Cows were randomly assigned by parity and calving date to receive one of the following pre-synchronization treatments: (1) 25mg of PGF(2alpha) (im) on day -35 and day -21 (PGF-PGF) or (2) 100 microg of GnRH (im) on day -14 (GnRH). Fewer (P<0.05) GnRH- (49%, 41/84) than PGF-PGF-pretreated cows (65%, 49/75) were detected in estrus, however, overall pregnancy rates were not affected by pre-synchronization treatment (30 versus 32%, respectively). In Experiment 2, lactating Holstein cows received 100 microg of GnRH (im) on day -7, 25mg of PGF(2alpha) (im) on day 0 and TAI at 60-64 h after PGF(2alpha). Cows were randomized by parity and postpartum interval into pre- and post-synchronization treatments in a 2 x 2 factorial design. Pre-synchronization treatments included: (1) 25mg of PGF(2alpha) (im) on day -35 and on day -21 (PGF-PGF; n=168) or (2) 25mg of PGF(2alpha) (im) on day -21 and 100 microg of GnRH (im) on day -14 (PGF-GnRH; n=180). Within each pre-synchronization treatment, cows were further allocated by parity and postpartum interval to receive as a post-synchronization treatment 100 microg of GnRH (im) at either 48 h (Ovsynch; n=175) or 60-64 h (Cosynch; n=173) after PGF(2alpha). Pregnancy rates at TAI were not affected by pre- (PGF-PGF=26%, 44/168 versus PGF-GnRH=24%, 44/180) or post-synchronization treatments (Ovsynch=29%, 50/175 versus Cosynch=22%, 38/173). However, the numeric shift towards reduced pregnancy rates in Cosynch-treated cows suggests the 12h interval between GnRH and AI may be important to optimize conception rates in GnRH-PGF(2alpha)-based TAI protocols in dairy cattle. In conclusion, each of the pre-synchronization protocols evaluated in present study performed with comparable efficacy. Although the Cosynch protocol facilitates more efficient labor utilization, numeric trends toward reduced conception warrants further investigation.

Self-administration of either nicotine (NIC) or ethanol (ETH) has been extensively studied. This study addressed for the first time the self-administration of both substances when offered together. Male and female rats of different ages were offered NIC and ETH using the two- or three-bottle free-choice method. When NIC and ETH were offered together at different concentrations to young male rats (about 45 days old), intake of NIC increased with increasing NIC concentrations, and intake of ETH increased with decreasing ETH concentrations, but these effects were independent of the presence of the second drug. These rats also consumed the same amounts of NIC or ETH regardless of whether offered individually or together. A prior choice of only NIC or ETH did not affect a subsequent intake of both drugs offered together. A choice of both drugs for 24 h for several days followed by a choice for only 2 h for several days showed the same intake of NIC but a decreased intake of ETH for the shorter period. Young female rats (about 45 days old) and older male rats (about 75 days old) consumed the same amounts of NIC but less ETH than did the young male rats. These results show that young male rats voluntarily consume NIC and ETH independently of each other and that preexposure to one drug does not affect the subsequent intake of both drugs in combination. The data also suggest that these drugs act on different reward centers which have to be 'satisfied' independently of each other., (Copyright 2003 S. Karger AG, Basel)

This study compared the efficacy of two sources of PGF2alpha on the reproductive performance of virgin beef heifers, after synchronization of estrus using melengestrol acetate (MGA) and PGF2alpha. Angus-based heifers (n = 1002) in five herds were fed 0.5 mg per head per day of MGA for 14 days. Nineteen days after the last day of MGA feeding, heifers were randomly assigned to receive (i.m.) either 0.5 mg cloprostenol (n = 504; Estrumate, E) or 25 mg dinoprost tromethamine (n = 498; Lutalyse, L) as a source of exogenous PGF2alpha. Heifers were observed twice daily for 5 days for signs of estrus and artificially inseminated 8-12 h later, except in herd A, wherein animals not detected in estrus by 80 h after PGF2alpha were mass-mated and no longer monitored for signs of estrus. Estrumate and Lutalyse were equally (P > 0.1) effective among all response variables evaluated, including estrus response (E, 89% and L, 86%), conception rate (E, 67% and L, 67%), and synchronized pregnancy rate (E, 61% and L, 57%). Synchrony of estrus was not affected (P > 0.1) by PGF2alpha source, and peak estrus response occurred 60 h post-PGF for both treatments. Conception rate to timed insemination was not different (P > 0.1) among Estrumate- and Lutalyse-treated heifers within herd A (14%, 4/28 and 7%, 2/29, respectively). Herd had a significant (P < 0.05) effect on all indicators of reproductive performance. Conception rates within herds A and D were influenced by technician (P < 0.05), however, this effect was balanced across treatments and no treatment by technician interaction was detected. In conclusion, when administered 19 days after a 14-day MGA feeding period, cloprostenol and dinoprost tromethamine are equally efficacious for synchronous induction of a fertile estrus in virgin beef heifers.

The efficacy of GnRH and PGF2alpha (7-day injection interval) for estrus synchronization is diminished by estrous expression before PGF2alpha (premature estrus; PE). Effects of modifications to GnRH-PGF2alpha protocols on the incidence of PE and other indicators of reproductive performance were evaluated. In Experiment 1, Angus-based crossbred cows (n=51) received 25 mg of PGF2alpha i.m. on Day 0. Animals were randomly assigned by parity and interval postpartum to receive GnRH 100 microg i.m. on either Day -7 or Day -6. Estrous detection and AI were conducted from Day -3 to Day 5. Treatment had no effect on the incidence of PE, estrous response, conception rate per AI or synchronized pregnancy rate (6- vs. 7-day interval; 8 vs. 15%; 92 vs. 93%; 77 vs. 76%; 71 vs. 70%, respectively). In Experiment 2, Angus cows (n=150) received GnRH 100 microg i.m. on Day -7 and 25 mg PGF2alpha i.m. on Day 0. Animals were randomly assigned by parity, interval postpartum, and body condition score to receive either no further treatment (Control) or 0.5 mg melengestrol acetate/hd/d from Day -7 to Day -1 (MGA). Estrous detection and AI were conducted from Day -2 to Day 7. Fewer (P < 0.05) MGA-treated cows were detected in PE (0%) compared to controls (7%). Treatment had no effect on estrous response or synchronized pregnancy rates (Control vs. MGA; 78 vs. 84%; 52 vs. 60%, respectively). Conception rate per AI of cows > or = 60 days postpartum were not affected by treatment (Control vs. MGA; 79 vs. 73%) however, control cows < 60 days postpartum tended (P < 0.10) to have lower conception rates per AI (39%) than did their MGA-treated counterparts (69%). In summary, 6- and 7-day GnRH-PGF2alpha injection intervals resulted in similar synchronized reproductive performance. Inclusion of MGA feeding between GnRH and PGF2alpha injections eliminated the occurrence of premature estrus and improved conception rate per AI of late-calving cows.

Fixed-time AI (TAI) after GnRH-PGF(2alpha)-GnRH treatment is a method to achieve pregnancies in dairy herds without estrous detection. However, cows that fail to respond to the initial GnRH may have compromised TAI conception rates due to asynchronous ovarian response. This study documented the percentage of GnRH-treated Holstein cows (n=345) in two herds that displayed estrus at an inopportune time for optimum TAI conception rate (< or =48h post-PGF(2alpha); premature estrus (PE)) and compared conception rates of two TAI protocols in cows that did not display PE. At biweekly herd health exams, cows diagnosed as not pregnant to a previous AI and cows >80 days postpartum with no AI were treated with 100 microg GnRH (day -7) and 25mg PGF(2alpha) (day 0). Cows detected in PE by twice-daily visual observation from day -7 to day 2 were bred by AI 8-12h later. Cows not detected in PE were randomly assigned by parity, body condition score, and postpartum interval to receive either: (1) 100microg GnRH at 48h after PGF(2alpha) and TAI 16 to 18h later (Ovsynch); or (2) TAI at 72h post-PGF(2alpha) and a concurrent 100 microg GnRH injection to those cows not detected in estrus between 48 and 72h post-PGF(2alpha) (modified Ovsynch (MOV)). All hormone injections were im. Twenty percent (68/345) of the cows were detected in estrus before 48 after PGF(2alpha), of which 5% (17/345) were detected in estrus before PGF(2alpha) (< or =day 0). Herd influenced the percentage of cows in the PE group (herd A versus herd B; 25% versus 14%; P<0.05). Conception rates were not affected by treatment (PE versus Ovsynch versus MOV; 32% (21/65) versus 30% (37/125) versus 32% (47/145); P>0.10). However, within MOV-treated cows, conception rates were greater (P<0.05) in cows detected in estrus (46% (23/50)) compared with cows not detected in estrus (25% (24/95)). In conclusion, 20% of GnRH-treated cows displayed PE and necessitates estrous detection during this period if maximal pregnancy rates are to be achieved. Although additional estrous detection is required compared to Ovsynch, reduced cow handling and hormone usage, efficient use of expensive semen through greater conception rates in cows detected in estrus, and comparable TAI conception rates, suggests the MOV protocol may be a cost effective alternative to Ovsynch in many dairy herd reproductive management programs.