Genome-wide association study for response to vaccination in Angus calves1.

BACKGROUND: Bovine respiratory disease complex (BRDC) is one of the most important sources of loss within the beef cattle industry in the USA. Steps have been taken to reduce the incidence of BRDC through vaccination. Despite the effectiveness of vaccines, large proportions of cattle still experience morbidity and mortality. Identification of genomic regions that are associated with variation in response to vaccination would allow for the selection of individuals genetically predisposed to respond to vaccination based on specific markers, while heritability and accuracy estimates would help facilitate genomic selection. This in turn may lead to selection for beef cattle herds that may have lower incidence rate of BRDC after vaccination. This study utilizes an Angus herd of more than 2000 head of cattle to identify these regions of association. RESULTS: Genome wide association studies were performed for viral neutralization antibody level and response to vaccination traits against four different viruses associated with BRDC: bovine viral diarrhea virus 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus (BHV1). A total of six 1-Mb windows were associated with greater than 1% of the genetic variance for the analyzed vaccination response traits. Heritabilities ranged from 0.08 to 0.21 and prediction accuracy ranged from 0.01 to 0.33 across 7 different vaccination traits. CONCLUSIONS: Although six 1-Mb windows were identified as associated with 1% or greater genetic variance for viral neutralization antibody level and response to vaccination traits, few genes around these windows could readily be considered candidates. This indicates the need for further functional genomic annotation, as these regions appear to be gene deserts. Traits ranged from lowly to moderately heritable, which indicated the potential for selection of individuals that are genetically pre-disposed to respond to vaccination. The relatively low amount of genetic variance accounted for by any 1-Mb window indicated that viral neutralization antibody level and response to vaccination traits are polygenic in nature. Selection for these traits is possible, but likely to be slow due to the low heritabilities and absence of markers with high genetic variation associated with them.

Evaluation of responses to vaccination of Angus cattle for four viruses that contribute to bovine respiratory disease complex.

Although vaccination is an effective measure in reducing the risk of bovine respiratory disease complex (BRDC) in cattle, BRDC losses remain significant. Increasing the efficacy of vaccination depends on elucidating the protective immune response to different antigens included in vaccines, determining the best timing for vaccination, and understanding the impact of the age of the calf on vaccination. This study measured the serum antibodies present in calves following vaccination against 4 viruses commonly associated with BRDC: bovine viral diarrhea virus type 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus 1 (BHV1). Serum antibody titers were measured in more than 1,600 calves at 3-wk intervals starting at the time of the first vaccination. This first vaccination occurred at weaning for approximately half of the individuals and 3 wk before weaning for the other half. Dam age (years), time of weaning (initial vaccination or booster vaccination), and age of calf within year-season (days within year-season) classification all were found to have a significant effect on measured traits such as the initial titer and overall response. An increased initial titer was negatively correlated with each response trait (initial, booster, and overall response). Calves that were weaned at initial vaccination had greater overall antibody response to BVDV1 and BVDV2 compared with calves weaned 3 wk before initial vaccination. In contrast, calves given their initial vaccination 3 wk before weaning had greater overall antibody response to BRSV and BHV1 compared with calves that were vaccinated at weaning. Furthermore, the circulating antibody titer at which each virus needed to be below for an individual calf to positively respond to vaccination was determined (log titer of 0.38 for BVDV1, 1.5 for BVDV2, 3.88 for BRSV, and 1.5 for BHV1). This information can be used to improve vaccination protocols to allow for a greater response rate of individuals to vaccination and, hopefully, improved protection.

Management of the axilla: has Z0011 had an impact?

BACKGROUND: Management of axillary disease in breast cancer has evolved significantly over the last two decades with the introduction of SLNB and a trend towards less radical surgery. Data from the American College of Surgeons Oncology Group Z0011 trial proposes that not all patients with positive axillary lymph nodes require completion axillary dissection. AIMS: The aim of this study was to determine whether there has been a change in practice patterns for axillary management in Ireland since the publication of this 'practice-changing' trial. METHODS: A review of breast cancers managed in the 12 months prior to publication of Z0011 (pre-Z0011) and comparison with those managed in the following 12 months (post-Z0011) was undertaken in three tertiary referral breast cancer centres. Patients with a positive SLNB were identified, and clinicopathologic data and subsequent management was compared between the two cohorts. RESULTS: There were 708 SLNB performed during the study period; 326 pre-Z0011 and 382 post-Z0011. There was no difference in the rate of SLN positivity between the two cohorts: 29.1 % had a positive SLN pre-Z0011 and 29.3 % were positive post-Z0011. There were a significantly lower number of axillary clearances performed in SLN-positive patients in the post-Z0011 period (71.4 %) compared to the pre-Z011 period (93.7 %, p = 0.0022 Chi-square). Of the patients with tumour characteristics meeting the Z0011 inclusion criteria in the initial 12 months of the study, 92.3 % underwent ALND compared with 65.6 % in the final 12 months of the study (p = 0.0006 Chi-square). CONCLUSIONS: There has been a change in clinical practice since the publication of the Z0011 trial, illustrated by a decrease in the rate of axillary clearance in node-positive breast cancers.

Description of bovine major histocompatibility complex class IIa haplotypes using parthenogenetic embryo-derived cells.

In this study, we report an approach to characterize individual BoLA haplotypes using cells from parthenogenetic bovine embryos derived from slaughterhouse ovaries. Eight of the 15 parthenogenetic embryos so obtained had not undergone meiotic recombination on the BoLA region and were suitable to describe BoLA haplotypes. Detailed analysis of the BoLA class IIa region identified seven different class IIa haplotypes, including six not previously described and two new alleles of BoLA-DQA and one BoLA-DQB. Our method provided reliable sources of homozygous DNA to describe BoLA haplotypes.

Breast clinic referrals: can mastalgia be managed in primary care?

BACKGROUND: Centralisation of breast cancer services in Ireland has resulted in a significant increase in the number of patients attending symptomatic breast units (SBU). A considerable proportion of patients referred to SBU present with non-suspicious symptoms and fall into a "low-risk" category for breast cancer. It has been proposed that consideration be given to a primary care-delivered service for these patients. AIM: To evaluate SBU attendances and correlate with diagnosis to identify a cohort of patients who may be suitable for management in the primary care setting. METHODS: Data were collected from a prospectively maintained database on patients attending SBU at two tertiary referral centres (Beaumont Hospital and University College Hospital Galway) from January 2011 to 2012. Reasons for attendance, outcome of triple-assessment and incidence of malignancy were analysed. RESULTS: 14,325 patients underwent triple assessment at the SBU in this time period. 5,841 patients were referred with mastalgia, of whom 3,331 (57 %) reported mastalgia as the only symptom. The incidence of breast cancer in patients presenting with mastalgia alone was 1.2 %. All patients diagnosed with breast cancer in this cohort were over 35 years of age. CONCLUSION: The incidence of breast cancer in patients referred to SBU with mastalgia as an isolated symptom is extremely low. Patients under 35 years of age, with mastalgia as an isolated symptom do not require breast imaging and have a sufficiently low risk of breast cancer that they may be suitable for management in the primary care setting.

Evaluation of response to bovine viral diarrhea virus type 2 vaccination and timing of weaning on yearling ultrasound body composition, performance, and carcass quality traits in Angus calves.

There are concerns about antagonisms between immunity and animal productivity in livestock production. The objective of this study was to evaluate the effect of antibody levels through a response to vaccination protocol, weaning timing, and their interaction on performance and carcass quality traits in Angus beef cattle. Final antibody level and response to vaccination were based on neutralizing serum antibodies against bovine viral diarrhea virus type 2 (BVDV2). Calves were followed through development and the feedlot phase, with collection of yearling ultrasound (n=957), preharvest (n=762), and carcass (n=673) data. In this study, 48% of the animals were observed to have positively responded to the vaccine, as evidenced by higher final antibody levels compared to prevaccination antibody levels. Increased final antibody levels were significantly (P<0.05) associated with increased yearling weight and increased subcutaneous fat over the rump. An interaction between final antibody level and weaning time also was associated (P<0.05) with Warner-Bratzler shear force (WBSF) and meat pH, with a favorable, negative relationship between final antibody and WBSF in calves weaned at initial vaccination. Overall antibody response by wean time interaction had a significant (P<0.05) association with ADG and meat pH, with calves weaned at initial vaccination having a favorable, positive relationship between overall antibody response and ADG. Under both the final antibody and overall antibody response models, animals weaned at initial vaccination had significantly (P<0.05) lower intramuscular fat at yearling time and conversely higher harvest weight than animals weaned at the booster vaccination. When antibody response was grouped (none, low, high), a significant interaction (P<0.05) between antibody response group and weaning time was identified for ADG, harvest weight, and HCW. Animals weaned at the initial vaccination in the high antibody response group had the advantage for ADG, harvest weight, and HCW compared to animals in the high-response group that were weaned at booster vaccination. Linear increases in antibody response generally did not have negative effects on performance or carcass quality traits in finished cattle (P>0.05). Therefore, producers should not be concerned about decreased production or quality attributes as a result of developing a robust antibody response to vaccination for BVDV2 in beef cattle.

An evaluation of circulating bovine viral diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves.

Vaccination against viruses has been shown to help prevent bovine respiratory disease in cattle. However, both passively acquired maternal antibody concentration and calf age have been shown to impact the ability of the immune system of a calf to respond to vaccination. The objectives of this study were to identify and evaluate environmental and management factors that affect 1) passively acquired bovine viral diarrhea virus (BVDV) type 2 antibody level, 2) decay rate of passively acquired BVDV type 2 antibody level, and 3) responses to BVDV type 2 vaccinations. A 2-shot modified live vaccine was administered to 1,004 Angus calves that were weaned at either the initial vaccination (n = 508) or the booster vaccination (n = 496). Calves weaned at the initial vaccination averaged 139 d whereas calves weaned at booster vaccination averaged 128 d of age. Bovine viral diarrhea virus type 2 antibodies were measured in 3 approximately 21-d intervals, serially collected serum samples to quantify antibody levels at initiation and end of vaccination protocol in addition to responses to initial, booster, and overall vaccination protocol. Amount of passively transferred antibody in the calf increased as dam age increased from 2 to 6 yr (P < 0.05) with no differences after dams reached 6 yr (P > 0.05). Calf age nested within birth year-season and dam age affected both initial and final antibody level, initial response, booster response, and overall antibody response to vaccination. The level of circulating, passively acquired maternal antibodies present at the time of vaccination had a significant (P < 0.05) negative effect on antibody responses to vaccination (initial response, booster response, and overall response). Calves that were weaned at the time of initial vaccination had significantly (P < 0.05) greater final antibody level, initial response, and overall response to vaccination than animals weaned at booster vaccination. In order for a calf to mount an overall antibody response to vaccination, maternal antibodies in circulation need to be less than 3.12 titers. However, the age at which a calf reached this antibody threshold was dependent on dam age. This information will help cattle managers and consultants design vaccination protocols to successfully mount an antibody response to vaccination.

Nurses' clinical decision-making regarding the management of pain.

Effective pain management remains an elusive goal within the profession of nursing. While considerable improvement has occurred, patients continue to experience inappropriate levels of pain. To date, research has focused on objective factors that influence pain management. Few studies have examined attitudinal factors that may influence nurses' decision-making. This quasi-experiment was based on preliminary data showing that nurses' preconceived notions regarding certain patient groups influenced their management of pain. An intervention was tested for its' effect on nurses' preconceived notions regarding specific patient groups. A significant difference in a positive direction was found. Nurses were more willing to spend time and energy managing pain across all patient groups following the intervention.

Nurses' clinical decision-making regarding the management of pain.

Effective pain management remains an elusive goal within the profession of nursing. While considerable improvement has occurred, patients continue to experience inappropriate levels of pain. To date, research has focused on objective factors that influence pain management. Few studies have examined attitudinal factors that may influence nurses' decision-making. This quasi-experiment was based on preliminary data showing that nurses' preconceived notions regarding certain patient groups influenced their management of pain. An intervention was tested for its' effect on nurses' preconceived notions regarding specific patient groups. A significant difference in a positive direction was found. Nurses were more willing to spend time and energy managing pain across all patient groups following the intervention.

Fetus in fetu: a rare cause of a neonatal mass.

Fetus in fetu is an unusual digression from the normal twinning process which often presents as a mass in neonates. Approximately 80 reports have been documented in the literature to date. The increasing use of routine obstetric ultrasound has identified more cases during the antenatal period. This allows more time for both the neonatology team and the parents to develop a coordinated treatment plan for the anticipated child. We report a case of a fetus in fetu which was first seen as a complex cystic mass during antenatal ultrasound at 21 weeks and was confirmed by subsequent imaging and surgical treatment shortly after birth.

Uterine cervical extrarenal Wilms tumor managed without hysterectomy.

This report describes an unusual case of uterine cervical Wilms tumor treated successfully without hysterectomy or radiation therapy. The 12-year-old white girl developed a persistent vaginal discharge. Her pelvic examination revealed a large mass involving the entire upper vagina, obscuring the cervix. Biopsy of the mass was consistent with Wilms tumor with favorable histology. The tumor was not initially resected because the resection would involve hysterectomy and partial resection of the bladder wall. The patient was treated with preexcisional chemotherapy consisted of alternating vincristine, doxorubicin, cyclophosphamide and carboplatin/etoposide. Repeat magnetic resonance imaging after 5 weeks of chemotherapy demonstrated marked reduction of the tumor size. The tumor was easily removed by transsection of the stalk followed by cold-knife conization of the cervix. The patient received four more cycles of chemotherapy and remained in complete remission 12 months after completion of chemotherapy. This report suggests that in selected cases, chemotherapy can reduce tumor size sufficiently in patients with bulky cervical Wilms tumor to allow local resection and avoid hysterectomy.

Laparoscopic pyloromyotomy.

Extramucosal pyloromyotomy is a method with predictable morbidity and outcome for the cure of infantile hypertrophic pyloric stenosis. The method created by Ramstedt is successfully performed using a laparoscopic approach. Preliminary reports, including 266 cases treated by laparoscopic pyloromyotomy (LP), suggest that morbidity is comparable to that of open approaches. Advantages of LP include superior cosmetic result and no reported wound infections to date. For the experienced laparoscopic surgeon, LP is an precise and efficient technique, and the preferred method for the management of infantile hypertrophic pyloric stenosis.

Identity of bovine growth hormone and peptidylglycine monooxygenase.

The C-terminal alpha-amidation of peptides is one of the most important events in prohormone and neuropeptide processing. Peptide amidation is a two-step process catalyzed by peptidylglycine (hydroxylating) monooxygenase (B. A. Eipper et al., 1983, Proc. Natl. Acad. Sci. USA 80, 5144-5148) followed by dismutation of the resultant hydroxylated peptide to peptide amide and glyoxylate, stimulated by alpha-hydroxyglycine amidating dealkylase (K. Takahashi et al., 1990, Arch. Biochem. Biophys. 169, 524-530). Previous reports on peptidylglycine monooxygenase from bovine pituitary have generated substantial disagreement as to its molecular size. We have reinvestigated the purification of this enzyme and we find that peptidylglycine monooxygenase activity from fresh bovine pituitary is entirely due to a previously unrecognized catalytic function of growth hormone (somatotropin).

Laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis: report of 11 cases.

Pyloromyotomy remains the standard of care for the treatment of infantile hypertrophic pyloric stenosis. Open pyloromyotomy is effective and is the gold-standard technique. The authors report on the techniques of laparoscopic pyloromyotomy. The clinical courses of the first 11 infants treated with laparoscopic pyloromyotomy we with the courses of 14 infants treated recently with open pyloromyotomy. The average surgical time for the laparoscopic group was 25.4 minutes. The average time (postoperatively) until full feedings was 19.0 hours. In the open pyloromyotomy group the average surgical time was 26.1 minutes, and the time until full feedings was 23.2 hours. These results are not significantly different. When compared with open pyloromyotomy, the laparoscopic approach appears to be equally safe and effective, with superior cosmetic results. The authors believe that laparoscopic pyloromyotomy is an excellent alternative procedure for the management of hypertrophic pyloric stenosis.

Diagnostic pneumoperitoneum accurately predicts the presence of patent processus vaginalis.

Ninety-four infants with unilateral indirect inguinal hernia underwent repair and diagnostic pneumoperitoneum (DPP). Contralateral groin exploration was performed in all patients including those with a negative DPP result. Thirty-seven (39%) of the 94 patients had a positive DPP result, and 36 of 37 (97%) had a patent processus vaginalis (PPV) on the side contralateral to the clinical hernia. Fifty-seven (61%) of the 94 patients had a negative DPP result, and 54 (95%) of these had no PPV. Female patients had a 1:1 correlation between DPP and PPV. DPP can predict the presence of PPV in the contralateral groin of patients with unilateral hernia with precision and minimizes the need for diagnostic groin exploration.

Gastric carcinoma in children.

Primary gastric carcinoma accounts for only 0.05% of pediatric gastrointestinal malignancies. The pattern, presentation, and location of childhood gastric carcinoma are similar to those of adult gastric carcinoma. Diagnosis is based on a high index of suspicion in children who present with symptoms mimicking acid peptic disease. Delay in diagnosis is common and avoided by early upper gastrointestinal radiography and endoscopy with biopsy. Surgical therapy alone may prolong survival but thus far it has proven only palliative. The role of chemotherapy and radiation in gastric carcinoma is still not well defined, although some new studies in adults may support the use of etoposide, doxorubicin, and cisplatin as primary therapy or combined with surgery and radiation. Long-term survival in children is rare. We present the case of a 3-year survivor, free of disease, treated with resection and chemotherapy.

Blunt bile duct injuries in children.

Three of 87 children with blunt liver injuries initially managed without operation required late intervention for bile leakage. Abdominal computed tomography scans in these patients showed liver injuries extending into the porta hepatis. Clinical courses were characterized by persistent abdominal pain, low-grade fever, and prolonged ileus. Radionucleide scan confirmed the suspicion of bile leakage. One patient had complete transection of the common bile duct, which was repaired surgically. Another had partial transection of the left hepatic duct, managed successfully with transampullary biliary decompression. The third patient with an intrahepatic injury was managed with a drain placed at celiotomy. Nonoperative management of blunt pediatric liver injuries carries a risk of persistent bile leakage. Radionucleide scan and endoscopic retrograde cholangiopancreatography are reliable modes of diagnosis and localization. Transampullary biliary decompression is a newer, effective modality for management of the proximal and/or partial bile duct injuries. Treatment must be individualized according to the site and extent of injury.