Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

Outcomes and toxicities in oligometastatic patients treated with stereotactic body radiotherapy for adrenal gland metastases: A multi-institutional retrospective study.

BACKGROUND: Studies reporting SBRT outcomes in oligometastatic patients with adrenal gland metastases (AGM) are limited. Herein, we present a multi-institutional analysis of oligometastatic patients treated with SBRT for AGM. MATERIAL/METHODS: The Consortium for Oligometastases Research (CORE) is among the largest retrospective series of patients with oligometastases. Among CORE patients, those treated with SBRT for AGM were included. Clinical and dosimetric data were collected. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one oligometastases is present.Competing risk analysis was used to estimate actuarial cumulative local recurrence (LR) and widespread progression (WP). Kaplan-Meier method was used to report overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Treatment related toxicities were also reported. RESULTS: The analysis included 47 patients with 57 adrenal lesions. Median follow-up was 18.2 months. Median LRFS, PFS, and OS were 15.3, 5.3, and 19.1 months, respectively. A minimum PTV dose BED10 > 46 Gy was associated with an improved OS and LRFS. A prescribed BED10 > 70 Gy was an independent predictor of a lower LR probability. AMB>10 cc was an independent predictor of a lower risk for WP. Only one patient developed an acute Grade 3 toxicity consisting of abdominal pain. CONCLUSION: SBRT to AGM achieved a satisfactory local control and OS in oligometastatic patients. High minimum PTV dose and BED10 prescription doses were predictive of improved LR and OS, respectively. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

Outcomes Following Hypofractionated Stereotactic Radiotherapy to the Cavity After Surgery for Melanoma Brain Metastases.

AIMS: Hypofractionated stereotactic radiotherapy (HSRT) to the cavity after surgical resection of brain metastases improves local control. Most reported cohorts include few patients with melanoma, a population known to have high rates of recurrence and neurological death. We aimed to assess outcomes in patients with melanoma brain metastases who received HSRT after surgery at two Australian institutions. MATERIALS AND METHODS: A retrospective analysis was carried out including patients treated between January 2012 and May 2020. HSRT was recommended for patients with melanoma brain metastases at high risk of local recurrence after surgery. Treatment was delivered using appropriately commissioned linear accelerators. Routine follow-up included surveillance magnetic resonance imaging brain every 3 months for at least 2 years. Primary outcomes were overall survival, local control, incidence of radiological radionecrosis and symptomatic radionecrosis. RESULTS: There were 63 cavities identified in 57 patients. The most common HSRT dose prescriptions were 24 Gy in three fractions and 27.5 Gy in five fractions. The median follow-up was 32 months in survivors. Local control was 90% at 1 year, 83% at 2 years and 76% at 3 years. Subtotal brain metastases resection (hazard ratio 12.5; 95% confidence interval 1.4-111; P = 0.0238) was associated with more local recurrence. Overall survival was 64% at 1 year, 45% at 2 years and 40% at 3 years. There were 10 radiological radionecrosis events (16% of cavities) during the study period, with 5% at 1 year and 8% at 2 years after HSRT. The median time to onset of radiological radionecrosis was 21 months (range 6-56). Of these events, three became symptomatic (5%) during the study period at a median time to onset of 26 months (range 21-32). CONCLUSION: Cavity HSRT is associated with high rates of local control in patients with melanoma brain metastases. Subtotal resection strongly predicts for local recurrence after HSRT. Symptomatic radionecrosis occurred in 5% of cavities but increased to 8% of longer-term survivors.

One-year implant survival following lateral window sinus augmentation using plasma rich in growth factors (PRGF): a retrospective study.

BACKGROUND: The aim of this study was to assess one-year implant survival after lateral window sinus augmentation using PRGF combined with various bone grafting materials. MATERIAL AND METHODS: This was a retrospective chart review and radiographic analysis of patients that had undergone lateral window sinus augmentation with PRGF and had dental implants placed at least 6 months post augmentation. All implants included were followed up for at least one year after placement. Demographic, sinus and implant related characteristics (residual ridge height, sinus membrane perforation, type of graft material, implant length and width and ISQ at placement) were analyzed. RESULTS: A total of 31 patients with 39 sinus augmentations and 48 implants were included. The mean follow up was 22.8 ± 9.9 months. Implant survival was 95.8%, with 2 implants overall failing. Among all the variables assessed, the only one found to be associated with an increased risk for implant failure was the use of xenograft as bone grafting material in the sinus. CONCLUSIONS: Within the limitations of this study, dental implants placed in maxillary sinuses grafted with PRGF in combination with bone grafting materials, exhibit high implant survival rates after at least one year follow up.

Development and prospective in-patient proof-of-concept validation of a surface photogrammetry + CT-based volumetric motion model for lung radiotherapy.

PURPOSE: We develop and validate a motion model that uses real-time surface photogrammetry acquired concurrently with four-dimensional computed tomography (4DCT) to estimate respiration-induced changes within the entire irradiated volume, over arbitrarily many respiratory cycles. METHODS: A research, couch-mounted, VisionRT (VRT) system was used to acquire optical surface data (15 Hz, ROI = 15 × 20 cm2 ) from the thoraco-abdominal surface of a consented lung SBRT patient, concurrently with their standard-of-care 4DCT. The end-exhalation phase from the 4DCT was regarded as reference and for each remaining phase, deformation vector fields (DVFs) with respect to the reference phase were computed. To reduce dimensionality, the first two principal components (PCs) of the matrix of nine DVFs were calculated. In parallel, ten phase-averaged VRT surfaces were created. Surface DVFs and corresponding PCs were computed. A principal least squares regression was used to relate the PCs of surface DVF to those of volume DVFs, establishing a relationship between time-varying surface and the underlying time-varying volume. Proof-of-concept validation was performed during each treatment fraction by concurrently acquiring 30 s time series of real-time surface data and "ground truth" kV fluoroscopic data (FL). A ray-tracing algorithm was used to create a digitally reconstructed fluorograph (DRF), and motion trajectories of high-contrast, soft-tissue, anatomical features in the DRF were compared with those from kV FL. RESULTS: For five of the six fluoroscopic acquisition sessions, the model out-performed 4DCT in predicting contour Dice coefficient with respect to fluoroscopy-derived contours. Similarly, the model exhibited a marked improvement over 4DCT for patch positions on the diaphragm. Model patch position errors varied from 5 to -15 mm while 4DCT errors ranged between 5 and -22.4 mm. For one fluoroscopic acquisition, a marked change in the a priori internal-external correlation resulted in model errors comparable to those of 4DCT. CONCLUSIONS: We described the development and a proof-of-concept validation for a volumetric motion model that uses surface photogrammetry to correlate the time-varying thoraco-abdominal surface to the time-varying internal thoraco-abdominal volume. These early results indicate that the proposed approach can result in a marked improvement over 4DCT. While limited by the duration of the fluoroscopic acquisitions as well as the resolution of the acquired images, the DRF-based proof-of-concept technique developed here is model-agnostic, and therefore, has the potential to be used as an in-patient validation tool for other volumetric motion models.

Radiological Kinetics of Brain Metastases and Clinical Implications for Patients Treated With Stereotactic Radiosurgery.

AIMS: Select patients with brain metastases receive stereotactic radiosurgery (SRS) with the objective of improving survival and intracranial disease control. Brain metastases number and volume are prognostic factors used to inform patient selection. The aim of this study was to assess the rate of change of brain metastases size and number (growth kinetics) between the diagnostic and day of SRS magnetic resonance imaging (MRI) scans. MATERIALS AND METHODS: All patients treated with Gamma Knife SRS between October 2015 and April 2017 were included in this single-centre retrospective analysis. Brain metastases number and diameter were recorded at diagnosis and treatment. For patients with multiple brain metastases, the largest lesion was the index lesion. Distant intracranial control and overall survival were reported from the date of SRS. RESULTS: In total, 146 patients received 156 episodes of SRS. The median interval between diagnostic and SRS MRI was 20 days (range 1-68). Interval growth in the index lesion of at least 3 mm or the development of a new brain metastasis was noted in 60.2% of patients. This was associated with age less than 60 years (P = 0.001), Eastern Cooperative Oncology Group (ECOG) performance status 2 or above (P = 0.04), non-small cell lung carcinoma (NSCLC) (P = 0.03) or melanoma histologies (P = 0.05) and uncontrolled extracranial disease (P = 0.05). These patients were also more likely to develop distant intracranial recurrence (P = 0.046). Clinically significant growth was not associated with scan interval or differences in overall survival. The Kaplan-Meier estimate of probability of survival at 12 months was 59.3% (95% confidence interval 46.7-75.2%) for all patients. CONCLUSION: Intracranial progression between diagnosis and day of SRS is common. Risk factors are uncontrolled extracranial disease, poorer performance status, NSCLC or melanoma histologies and age less than 60 years. These patients would benefit from an MRI closer to treatment to inform patient selection and target delineation for SRS planning.

Stereotactic Ablative Body Radiotherapy for the Treatment of Spinal Oligometastases.

AIMS: To report multicentre outcomes of patients with spinal oligometastases treated with stereotactic ablative body radiotherapy (SABR). The primary objective was to estimate the widespread failure-free survival (WFFS) at 2 years - defined as freedom from metastases not amenable to local salvage therapy and death. MATERIALS AND METHODS: Patients with one to three metastases treated with spinal SABR between January 2010 and July 2014 at four academic institutions were included in this retrospective review. The median dose/fractionation was 24 Gy (range 16-52.5 Gy) in two fractions (range one to three) and the median biologically effective dose (α/ß=10) was 52.5 Gy (range 40-144.4 Gy). The WFFS, overall survival, freedom from local progression and toxicity rates were described using Kaplan-Meier statistics. RESULTS: In total, 60 patients with 72 spinal metastases were analysed. The median follow-up was 21 months. Patients had a median age of 66 years, Eastern Cooperative Oncology Group performance 0-1 in 97% and metachronous oligometastases in 85%. The 1 and 2 year WFFS rates were 67% (95% confidence interval 55-80) and 59% (95% confidence interval 47-75), respectively. The 1 and 2 year overall survival rates were 90% (95% confidence interval 83-98) and 76% (95% confidence interval 64-91), respectively. The 1 and 2 year freedom from local progression were 92% (95% confidence interval 85-99) and 86% (95% confidence interval 75-99), respectively. There were four cases (6.7%) of vertebral compression fracture and no cases of radiation myelopathy. CONCLUSION: Despite the use of relatively low biological doses respecting spinal cord constraints, SABR results in excellent 2 year local control rates with low morbidity. Through careful selection of patients with oligometastases, most patients are alive and free from widespread metastases at 2 years. This cohort warrants further investigation in clinical trials of SABR.

Radiotherapy in Glioblastoma: the Past, the Present and the Future.

The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment.

Diabetes mellitus and extrapulmonary tuberculosis: site distribution and risk of mortality.

Scarce data exist on the relationship between diabetes and extrapulmonary tuberculosis (EPTB). We evaluated whether diabetes impacts site of TB and risk of death in patients with EPTB. We evaluated a cohort of TB cases from the state of Georgia between 2009 and 2012. Patients aged ⩾16 years were classified by diabetes status according to medical records. Site of EPTB was determined by culture and/or state TB classification. Death was defined by all-cause mortality. Of 1325 eligible reported TB cases, 369 (27·8%) had any EPTB including 258 (19·5%) with only EPTB and 111 (8·4%) with pulmonary TB and EPTB. Of all TB cases, 158 had diabetes (11·9%). In multivariable analysis, the odds of any EPTB was similar in patients with and without diabetes [adjusted odds ratio 1·04, 95% confidence interval (CI) 0·70-1·56]. The risk of death was 23·8% in patients with EPTB and diabetes vs. 9·8% in those with no diabetes (P < 0·01); after adjusting for covariates the difference was not significant (aRR 1·19, 95% CI 0·54-2·63). Diabetes was common in patients with EPTB and risk of death was high. Improved understanding of the relationship between diabetes and EPTB is critical to determine the extent that diabetes affects TB diagnosis and clinical management.

A systematic review of non-surgical treatments for lentigo maligna.

Lentigo maligna (LM) is the most common melanocytic malignancy of the head and neck. If left untreated, LM can progress to lentigo maligna melanoma (LMM). Complete surgical excision is the gold standard for treatment, however, due to the location, size, and advanced age of patients, surgery is not always acceptable. As a result, there is ongoing interest in alternative, less invasive treatment modalities. The objective was to provide a structured review of key literature reporting the use of radiotherapy, imiquimod and laser therapy for the management of LM in patients where surgical resection is prohibited. An independent review was conducted following a comprehensive search of the National Library of Medicine using MEDLINE and PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases. Data were presented in tabular format, and crude data pooled to calculate mean recurrence rates for each therapy. 29 studies met the inclusion criteria: radiotherapy 10; topical imiquimod 10; laser therapies 9. Radiotherapy demostrated recurrence rates of up to 31% (mean 11.5%), with follow-up durations of 1-96 months. Topical imiquimod recurrence rates were up to 50% (mean 24.5%), with follow-up durations of 2-49 months. Laser therapy yielded recurrence rates of up to 100% (mean 34.4%), and follow-up durations of 8-78 months. in each of the treatment series the I(2) value measuring statistical heterogeneity exceeded the accepted threshold of 50% and as such a meta-analysis of included data were inappropriate. For non-surgical patients with LM, radiotherapy and topical imiquimod were efficacious treatments. Radiotherapy produced superior complete response rates and fewer recurrences than imiquimod although both are promising non-invasive modalities. There was no consistent body of evidence regarding laser therapy although response rates of up to 100% were reported in low quality studies. A prospective comparative trial is indicated and would provide accurate data on the long-term efficacy and overall utility of these treatments.

Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma.

BACKGROUND: Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy. PATIENTS AND METHODS: Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS). RESULTS: Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR [partial (PR) or complete response (CR)] was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis. CONCLUSIONS: Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

AIMS: To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. MATERIALS AND METHODS: OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. RESULTS: In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. CONCLUSION: Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status.

Hippocampal-sparing radiotherapy: the new standard of care for World Health Organization grade II and III gliomas?

The neurocognitive effects of cranial radiotherapy in patients with gliomas are well-recognised and may be related to the dose delivered to the hippocampi. Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be used to selectively spare the hippocampi without compromising the dose delivered to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is achievable in patients with World Health Organization (WHO) grade II and III gliomas. A retrospective review of consecutive patients with WHO grade II and III gliomas treated with IMRT at our institution between January 2009 and August 2012 was performed. Hippocampal-sparing was defined as a mean dose to at least one hippocampus of less than 30 Gy. The dose delivered to the tumour was never compromised to achieve the hippocampal dose constraint. Logistic regression analyses were performed to identify predictive factors for achieving hippocampal-sparing treatment. Eighteen patients were identified and hippocampal-sparing was achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and 11 patients had WHO grade III gliomas. The mean dose to the contralateral hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm3 were more likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7, p=0.03) and there was a trend with oligodendrogliomas and anaplastic oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed prospectively. The relationship between hippocampal dose and neurocognitive function in adults is currently under investigation.

Kidney paired donation: a payer perspective.

Kidney transplantation is the most cost-effective and clinically effective form of renal replacement therapy. Due to long wait times for deceased donors, kidney transplantation is not available to many patients with incompatible living donors. Increased access to kidney transplantation is a shared goal that can be achieved through kidney paired donation (KPD). A single, national system of KPD administered to a set of clinical and ethical standards determined by a consensus of stakeholders including recipients, donors, providers, payers and the United States federal government will provide the best opportunity to offer kidney transplantation to the most people and particularly to those currently unlikely to receive a transplant. We propose that this system will use uniform tissue typing algorithms and a computerized donor and recipient matching program using a national pool of willing donors. The proposed system can be managed best through a single administrative structure that takes advantage of uniform donor evaluation and management with a standardized organ acquisition charge that recognizes that the current lack of standardization contributes to delays in transplantation and payment to programs. This program will use the existing Organ Procurement Organization infrastructure to manage the logistics of organ acquisition, transportation and billing.

Adaptive immunity in the colostrum-deprived calf: response to early vaccination with Mycobacterium bovis strain bacille Calmette Guerin and ovalbumin.

Responses of the newborn calf to vaccination are frequently characterized by marginal antibody (Ab) responses. The present study evaluated effects of colostrum ingestion on the adaptive immune response of the preruminant calf to early vaccination. Colostrum-fed (CF) and colostrum-deprived (CD) calves were vaccinated at 2 d of age with Mycobacterium bovis, Pasteur strain of bacille Calmette Guerin (BCG), and ovalbumin (OVA) to track development of the adaptive immune response during the first 8 wk of life. Dams were also vaccinated with BCG prepartum. At wk 0, serum IgG(1), IgG(2), IgA, and IgM were elevated in CF calves, with IgG(1) predominating. In these calves, IgG(2), IgA, and IgM concentrations decreased with age. The CD calves, in contrast, had very low or undetectable serum immunoglobulin concentrations at wk 0 followed by an age-related increase in IgG(1), IgG(2), and IgM concentrations, suggesting endogenous production of these immunoglobulin classes. Immunoblot and ELISA analyses of Ab response to BCG vaccination indicated that colostrum ingestion was associated with measurable serum anti-mycobacterial Ab in CF calves during the first month postpartum, with substantially lower levels at 7 wk of age. Although mycobacteria-specific Ab was undetectable in CD calves at wk 0, it was present at 4 and 7 wk of age, suggesting that these calves, unlike CF calves, were capable of generating an Ab response to BCG vaccination. Antibody responses of CF and CD calves to vaccination with OVA, an antigen not present in the natural environment of dairy cattle, were of comparable magnitude and characterized by a progressive increase in Ab levels from birth (wk 0) to 7 wk of age. The disparate Ab responses of CF calves to BCG and OVA suggest that maternal antigenic experience or exposure influences Ab responses of the colostrum-fed preruminant calf to early vaccination. Ex vivo, antigen [OVA and M. bovis-derived purified protein derivative (PPDb)]-induced IFN-γ and nitric oxide responses of blood mononuclear cells (PBMC) from CF and CD calves were comparable at wk 0 and wk 7. As expected, responses were very low or nonexistent at wk 0. Responses for all calves were greater at wk 7 than at wk 0, suggesting a colostrum-independent maturation of the cell-mediated immune response capacity of the preruminant calf. The consistently greater proliferative responses of antigen-stimulated T-cell subsets at wk 7 versus wk 0 indicate the development of antigen-specific lymphocyte responses to early vaccination. Total numbers of blood leukocytes as well as numbers of lymphocytes and monocytes were unaffected by colostrum feeding; however, granulocyte numbers were higher in CD than in CF calves at wk 0. Granulocyte numbers decreased and monocyte numbers increased with age in all calves. Within the lymphocyte population, only natural killer (NK(+)) cell percentages were affected by colostrum ingestion, with higher percentages of NK(+) cells in CD calves at wk 0 and wk 7. Antigen-induced proliferation of lymphocyte subsets including IgM(+) cells was unaffected by colostrum ingestion. In conclusion, ingestion of colostrum within hours after birth inhibited the capacity of the calf to produce antigen-specific immunoglobulin (i.e., antibody) in response to vaccination, with little or no effect on cell-mediated immune responses. Although colostrum appeared to block endogenous antibody production, certain B-cell functions were retained. These findings will aid in development of new vaccination strategies for improving health of the preruminant calf.

"Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats.

The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive advantage.