Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children’s Oncology Group study Linabery, AM, EB Erhardt, MM Richardson, RF Ambinder, DL Friedman, SL Glaser, A Monnereau, LG Spector, JA Ross, and S Grufferman International Journal of Cancer 137(9), pdf, pp. 2163–2174 Online: May 19, 2015 http://onlinelibrary.wiley.com.libproxy.unm.edu/doi/10.1002/ijc.29589/full DOI: 10.1002/ijc.29589 Abstract Family history of lymphoid neoplasm (LN) is a strong and consistently observed Hodgkin lymphoma (HL) risk factor, although it has been only marginally examined in pediatric/adolescent patients. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL cases diagnosed at 0–14 years at Children’s Oncology Group institutions in 1989–2003. Detailed histories were captured by structured telephone interviews with parents of 517 cases and 783 controls. Epstein–Barr virus (EBV) RNA detection was performed for 355 available case tumors. Two analytic strategies were applied to estimate associations between family cancer history and pediatric/adolescent HL. In a standard case–control approach, multivariate conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). In a reconstructed cohort approach, each relative was included as a separate observation, and multivariate proportional hazards regression was used to produce hazard ratios (HRs) and 95% CIs. Using the latter, pediatric/adolescent HL was associated with a positive family history (HR = 1.20, 95% CI: 1.06–1.36), particularly early-onset cancers (HR = 1.30, 95% CI: 1.06–1.59) and those in the paternal lineage (HR = 1.38, 95% CI: 1.16–1.65), with a suggested association for LN in first-degree relatives (HR = 3.61, 95% CI: 0.87–15.01). There were no discernable patterns for EBV+ versus EBV– HL. The clustering of LN within pedigrees may signal shared genetic susceptibility or common environmental exposures. Heritable genetic risk variants have only recently begun to be discovered, however. These results are consistent with other studies and provide a compelling rationale for family-based studies to garner information about genetic susceptibility to HL.
... more

Family history of cancer and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group and the Utah Population Database Lupo, PJ, HE Danysh, SE Plon, K Curtin, D Malkin, S Hettmer, DS Hawkins, SX Skapek, LG Spector, K Papworth, B Melin, EB Erhardt, S Grufferman, and JD Schiffman Cancer Medicine 2015, 4(5), pdf, 781–790 Online: March 23, 2015 http://onlinelibrary.wiley.com/doi/10.1002/cam4.448/full DOI: 10.1002/cam4.448 Abstract Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case–control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Children’s Oncology Group (COG). Population-based controls (n = 322) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (ORs) and 95% confidence intervals (CI). Having a first-degree relative with a cancer history was more common in RMS cases than controls (ORs = 1.39, 95% CI: 0.97–1.98). Notably, this association was stronger among those with embryonal RMS (ORs = 2.44, 95% CI: 1.54–3.86). Moreover, having a first-degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (ORs = 2.37, 95% CI: 1.34–4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first-degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.
... more

Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials Rosenberg, GA, J Prestopnik, J Adair, BN Huisa, J Knoefel, A Caprihan, C Gasparovic, J Thompson, EB Erhardt, and R Schrader Journal of Neurology, Neurosurgery, and Psychiatry, pdf Online: January 24, 2015 http://jnnp.bmj.com/content/early/2015/01/23/jnnp-2014-309421.abstract doi: 10.1136/jnnp-2014-309421 Abstract Objectives Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. Methods We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-β1–42 and phosphorylated-τ181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses. Results An initial BDS of 6 or greater was significantly correlated with a final diagnosis of BD (p<0.05; area under the curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The most predictive of BD was the factor containing the inflammatory biomarkers of increased BBB permeability, elevated albumin index and reduced MMP-2 index (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD, and combining them improved the diagnostic accuracy. Conclusions Biomarkers predicted the diagnosis of the BD type of subcortical ischaemic vascular disease. Using pathophysiological biomarkers to select homogeneous groups of patients needs to be tested in targeted treatment trials.
... more

Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss) Scott LaPatra, Samantha Kao, Erik B. Erhardt, Irene Salinas Vaccine 33(6), pdf, pp. 771–776 Online: January 3, 2015 http://www.sciencedirect.com/science/article/pii/S0264410X14017101 DOI: 10.1016/j.vaccine.2014.12.055 Abstract Farmed fish are susceptible to different infectious disease agents including viruses and bacteria. Thus, multivalent vaccines or vaccination programs against two or more pathogens are valuable tools in aquaculture. Recently, nasal vaccines have been shown to be very effective in rainbow trout. The current study investigates, for the first time, the use of the nasal route in dual vaccination trials against two important aquatic diseases, infectious hematopoietic necrosis virus (IHN) and enteric red mouth (ERM) disease. Rainbow trout received live attenuated IHN virus (IHNV) vaccine and the ERM bacterin using four different vaccine delivery methods and were challenged with virulent IHNV or Yersinia ruckeri 7 (100 deg day) and 28 (400 deg day) days post-vaccination. The highest survival rates against IHNV at day 7 were obtained by nasal vaccination either when IHNV and ERM were delivered separately into each nare or when they were premixed and delivered to both nasal rosettes (group D). Protection at 28 days against IHNV was similar in all four vaccinated groups. Early protection against ERM was highest in fish that received each vaccine in separate nares (group B), whereas protection at 28 days was highest in the i.p. vaccinated group (group E), followed by the nasally vaccinated group (group B). Survival results were supported by histological observations of the left and right olfactory organ which showed strong immune responses one day (14 deg days) after vaccination in group B vaccinated fish. These data indicate that dual vaccination against two different pathogens via the nasal route is a very effective vaccination strategy for use in aquaculture, particularly when each nare is used separately during delivery. Further long-term studies should evaluate the contribution of adaptive immunity to the protection levels observed.
... more

Nasal immunity is an ancient arm of the mucosal immune system of vertebrates Luca Tacchi, Rami Musharrafieh, Erin T. Larragoite, Kyle Crossey, Erik B. Erhardt, Samuel A. M. Martin, Scott E. LaPatra, & Irene Salinas Nature Communications 5 (5205), pdf, doi: 10.1038/ncomms6205 Online 22 October 2014 http://www.nature.com/ncomms/2014/141022/ncomms6205/full/ncomms6205.html Abstract The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for millions of years. In terrestrial vertebrates such as birds and mammals, the nasopharynx-associated lymphoid tissue (NALT) represents a first line of immune defence. Here we propose that NALT is an ancient arm of the mucosal immune system not restricted to terrestrial vertebrates. We find that NALT is present in rainbow trout and that it resembles other teleost mucosa-associated lymphoid tissues. Trout NALT consists of diffuse lymphoid cells and lacks tonsils and adenoids. The predominant B-cell subset found in trout NALT are IgT + B cells, similar to skin and gut. The trout olfactory organ is colonized by abundant symbiotic bacteria, which are coated by trout secretory immunoglobulin. Trout NALT is capable of mounting strong anti-viral immune responses following nasal delivery of a live attenuated viral vaccine. Our results open up a new tool for the control of aquatic infectious diseases via nasal vaccination.
... more

Parental Military Service, Agent Orange Exposure, and the Risk of Rhabdomyosarcoma in Offspring Grufferman, S, PJ Lupo, RI Vogel, AF Olshan, EB Erhardt, and S Ognjanovic Journal of Pediatrics 2014 Dec; pdf, 165(6):1216–21 Online: September 18, 2014 http://www.jpeds.com/article/S0022-3476(14)00734-3/abstract DOI: 10.1016/j.jpeds.2014.08.009 Abstract OBJECTIVE: To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. STUDY DESIGN: Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. RESULTS: There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). CONCLUSIONS: We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.
... more

Reporting rate variation of childhood diseases in the pre-vaccine era Gunning, C, EB Erhardt, and HJ Wearing Proceedings of the Royal Society B 281 (1794) pp. 1-–9 Online: September 17, 2014 http://rspb.royalsocietypublishing.org//content/281/1794/20140886.abstract DOI: 10.1098/rspb.2014.0886 Abstract Incomplete observation is an important yet often neglected feature of observational ecological timeseries. In particular, observational case report timeseries of childhood diseases have played an important role in the formulation of mechanistic dynamical models of populations and metapopulations. Yet to our knowledge, no comprehensive study of childhood disease reporting probabilities (commonly referred to as reporting rates) has been conducted to date. Here, we provide a detailed analysis of measles and whooping cough reporting probabilities in pre-vaccine United States cities and states, as well as measles in cities of England and Wales. Overall, we find the variability between locations and diseases greatly exceeds that between methods or time periods. We demonstrate a strong relationship within location between diseases and within disease between geographical areas. In addition, we find that demographic covariates such as ethnic composition and school attendance explain a non-trivial proportion of reporting probability variation. Overall, our findings show that disease reporting is both variable and non-random and that completeness of reporting is influenced by disease identity, geography and socioeconomic factors. We suggest that variations in incomplete observation can be accounted for and that doing so can reveal ecologically important features that are otherwise obscured.
... more

Yield and Effects of Organic Nitrogen Fertilizer on Field-Grown Chinese Medicinal Plants in the United States Gardner, Z, EB Erhardt, E Shaikouskaya, JP Baek, and LE Craker Journal of Herbs, Spices & Medicinal Plants 21(1) pp. 9–22 Online: August 13, 2014 http://www.tandfonline.com/doi/abs/10.1080/10496475.2014.891092 DOI: 10.1080/10496475.2014.891092 Abstract There is an increased demand for Chinese medicinal plants in the U.S., with little known about the feasibility of production of these species outside of China. The purpose of this study was to develop basic agronomic data for selected Chinese medicinal plant species. Agastache rugosa, Schizonepeta tenuifolia, Leonurus japonicus, and Leonurus sibiricus were grown in a randomized complete block design with 0, 100, or 200 kg.ha−1 of nitrogen (N). At 100 kg.ha−1 of N, a significant increase in yield of all species was observed as compared to the 0 kg.ha−1 control. Average dry yield per plant at 100 kg.ha−1 of N was 44.7 g for A. rugosa herb, 52.6 g for S. tenuifolia inflorescences, 42.7 g for L. japonicus basal rosette, and 46.9 g for L. sibiricus basal rosette. Yields of A. rugosa and both Leonurus species increased significantly again at 200 kg.ha−1 of N as compared to 100 kg.ha−1, while the increase in yield between these two levels was slight for S. tenuifolia. Results from these trials indicate that all four of the selected species are suitable for cultivation in the northeastern U.S.
... more

Maternal and birth characteristics and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group Lupo, PJ, HE Danysh, SX Skapek, DS Hawkins, LG Spector, RZhou, MF Okcu, K Papworth, EB Erhardt, and S Grufferman Cancer Causes and Control 25 (7) pp 905-913 http://link.springer.com/article/10.1007/s10552-014-0390-6 Online: August 1, 2013 DOI: 10.1007/s10552-014-0390-6 Abstract Purpose Previous assessments of childhood rhabdomyosarcoma have indicated maternal and birth characteristics may be associated with tumor development; however, much work remains to identify novel and confirm suspected risk factors. Our objective was to evaluate the associations between maternal and birth characteristics and childhood rhabdomyosarcoma. Methods This case–control study included 322 cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls were identified using random digit dialing and were individually matched to cases on race, sex, and age. Families of the case and control subjects participated in a telephone interview, which captured information on maternal characteristics (birth control use, number of prenatal visits, anemia, and abnormal bleeding during pregnancy) and birth characteristics [birth weight, preterm birth, and type of delivery (vaginal vs. cesarean)]. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95 % confidence interval (CI) for each exposure, adjusted for age, race, sex, household income, and parental education. As the two most common histologic types of rhabdomyosarcoma are embryonal (n = 215) and alveolar (n = 66), we evaluated effect heterogeneity of these exposures. Results The only characteristic that was associated with childhood rhabdomyosarcoma, and statistically significant, was abnormal vaginal bleeding during pregnancy (OR 1.75, 95 % CI 1.12–2.74). Birth control use (OR 1.45, 95 % CI 0.96–2.18), anemia during pregnancy (OR 1.27, 95 % CI 0.81–1.99), and preterm birth (OR 2.51, 95 % CI 0.74–8.49) were positively associated with childhood rhabdomyosarcoma, but were not statistically significant. Low birth weight [adjusted odds ratios (aOR) 4.46, 95 % CI 1.41–14.1] and high birth weight (aOR 2.41, 95 % CI 1.09–5.35) were strongly associated with alveolar rhabdomyosarcoma. However, these factors did not display significant effect heterogeneity between histologic types (p > 0.15 for all characteristics). Conclusions Overall, we found little evidence that these maternal and birth characteristics are strongly associated with childhood rhabdomyosarcoma.
... more