A Love Story

pages 139-14

Influence of performance and genetic data on the sale price of seedstock bulls

Master of ScienceDepartment of Animal Sciences and IndustryMichael D. MacNeilJennifer M. BormannGenetic and phenotypic data are often provided to bull buyers at time of sale to aid producers in establishing economic value (pricing) of candidates for selection. This study evaluates the association between the information provided to bull buyers at time of sale and prices paid for bulls sold by two large seedstock operations located in Kansas (KS Ranch) and Colorado (CO Ranch). Data were gathered from 15 sale catalogs that documented bulls sold at auctions taking place from 2009 to 2013. In total, there were 39 potential predictor variables recorded for 2,601 Angus bulls for the KS Ranch; while 14 plausible predictor variables were recorded for 504 purebred and 1,399 Stabilizer bulls at the CO Ranch. Due to extensive multicollinearity between predictors, principal component (PC) analyses were conducted on the standardized predictors to reduce dimensionality within each ranch and genetic group. Eleven PC were considered to provide important meaningful information in summarizing the 39 predictors originally available to buyers at the KS Ranch. For both the purebred and Stabilizer bulls from each set of breed type data in the CO ranch, 6 principal components had eigenvalues greater than 1.0. Similar to the findings for the KS Ranch, these PCs also explained approximately 75% of the cumulative variability of the predictors. Sale prices were then regressed on the corresponding PC using a stepwise selection to identify the PC subset that most significantly explained the behavior of bull sale prices (P < 0.05). The final models explained approximately 63%, 37% and 58% of the variation in sale prices received for Angus, purebred and Stabilizer bulls, respectively. Interpretation of the eigenvectors for the PC having the greatest eigenvalues led to the conclusion that buyers put the most weight on growth traits followed by carcass characteristics and economic selection indices. However, no distinction of a specific variable’s numerical impact on price was determined

Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT

34612 Exploring the natural history of vitiligo in the United States: Findings from the VALIANT study

Vitiligo is a chronic autoimmune disease characterized by the destruction of melanocytes, resulting in depigmented skin lesions. Epidemiology studies in vitiligo are often limited to smaller sample sizes and rely on dermatology clinics as the source population. The population-based Vitiligo and Life Impact Among International Communities (VALIANT) study sought to understand the natural history of vitiligo among patients around the world. Here, data from US participants are presented. Participants were recruited via an online panel. Adults (aged ≥18 years) who self-reported a vitiligo diagnosis by a health care professional were eligible to participate. Of 608 US patients, 58% were male; median (range) age at the time of the survey was 36 (18–83) years. Mean disease duration was 11 years, with a mean 1.6 years between first noticing lesions and achieving a formal diagnosis. More than one-third of patients were previously misdiagnosed (37%), with higher rates among patients with darker skin types (67% for Fitzpatrick types IV–VI). Nearly two-thirds (62%) directly sought treatment for vitiligo; vitiligo was an incidental finding in the remaining 38%. Nearly two-thirds (64%) were diagnosed by a dermatologist, or a nurse practitioner or physician assistant in a dermatology-focused practice. Most patients (71%) noted a family history of vitiligo (comparable paternal vs maternal). Median body surface area affected by vitiligo was 4.23%, as measured by the self-assessed Vitiligo Extent Scale. In summary, these findings provide a new perspective on the diagnosis journey for patients with vitiligo and highlight the need for accurate, more timely diagnosis

Targeted copy number variant identification across the neurodegenerative disease spectrum

Background: Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. Methods: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). Results: In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer\u27s disease participant; (2) a duplication of exons 1–5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of \u3e3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7–11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. Conclusion: The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5–98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1–16 h after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS–MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle