Background

Genome-wide association study (GWAS) is a useful tool for detecting and characterizing traits of interest including those associated with disease resistance in soybean. The availability of 50,000 single nucleotide polymorphism (SNP) markers (SoySNP50K iSelect BeadChip; www.soybase.org ) on 19,652 soybean and wild soybean plant introductions (PIs) in the USDA Soybean Germplasm Collection allows for fast and robust identification of loci associated with a desired phenotype. By using a genome-wide marker set to predict phenotypic values, genomic prediction for phenotype-unknown but genotype-determined PIs has become possible. The goal of this study was to describe the genetic architecture associated with sensitivity to Tobacco ringspot virus (TRSV) infection in the USDA Soybean Germplasm Collection.

Results

TRSV-induced disease sensitivities of the 697 soybean PIs were rated on a one to five scale with plants rated as one exhibiting mild symptoms and plants rated as five displaying terminal bud necrosis (i.e., bud blight). The GWAS identified a single locus on soybean chromosome 2 strongly associated with TRSV sensitivity. Cross-validation showed a correlation of 0.55 (P < 0.01) to TRSV sensitivity without including the most significant SNP marker from the GWAS as a covariate, which was a better estimation compared to the mean separation by using significant SNPs. The genomic estimated breeding values for the remaining 18,955 unscreened soybean PIs in the USDA Soybean Germplasm Collection were obtained using the GAPIT R package. To evaluate the prediction accuracy, an additional 55 soybean accessions were evaluated for sensitivity to TRSV, which resulted in a correlation of 0.67 (P < 0.01) between actual and predicted severities.

Conclusion

A single locus responsible for TRSV sensitivity in soybean was identified on chromosome 2. Two leucine-rich repeat receptor-like kinase genes were located near the locus and may control sensitivity of soybean to TRSV infection. Furthermore, a comprehensive genomic prediction for TRSV sensitivity for all accessions in the USDA Soybean Germplasm Collection was completed.

A genome-wide association study (GWAS) was applied to detect single nucleotide polymorphisms (SNPs) significantly associated with resistance to Heterodera glycines (HG) also known as the soybean cyst nematode (SCN) in the core collection of common bean, Phaseolus vulgaris. There were 84,416 SNPs identified in 363 common bean accessions. GWAS identified SNPs on chromosome (Chr) 1 that were significantly associated with resistance to HG type 2.5.7. These SNPs were in linkage disequilibrium with a gene cluster orthologous to the three genes at the Rhg1 locus in soybean. A novel signal on Chr 7 was detected and associated with resistance to HG type 1.2.3.5.6.7. Genomic predictions (GPs) for resistance to these two SCN HG types in common bean achieved prediction accuracy of 0.52 and 0.41, respectively. Our study generated a high-quality SNP panel for 363 common bean accessions and demonstrated that both GWAS and GP were effective strategies to understand the genetic architecture of SCN resistance in common bean.

Background

Past research has shown discrepancies between the time of symptom onset for patients with acute coronary syndrome (ACS) as documented in the medical record (MR) and patients' recall of the time assessed through subject interviews done later by researchers.

Purpose

The aim of this study is to determine if there were differences between the time of symptom onset documented in the MR and subject interview taking into consideration sex, age group, and recall period for patients admitted to the emergency department for symptoms suggestive of ACS.

Methods

A secondary analysis was conducted on data from the PROMOTION (Patient Response to Myocardial Infarction Following a Teaching Intervention Offered by Nurses) trial, a multicenter randomized clinical trial to reduce patient prehospital delay to treatment in ACS.

Results

Of the 3522 subjects with CAD enrolled into the trial, 3087 subjects completed 2-year follow-up. Of these, 331 subjects sought treatment in the emergency department for ACS symptoms and 276 patients (83%) had complete information on the time of symptom onset from both sources. Of the 276 patients, 25 (9%) had differing times more than 48 hours and were thus excluded. The median difference between the 2 sources was 45.0 minutes. When both times were examined, there were no significant differences in time by sex (P = .720) or by age group (P = .188). The median number of days between the interview and the date of symptom onset was 29.5 days. There was a significant correlation between differences in the time of symptom onset and the length of recall period (rs = 0.148, P = .023). In multivariable modeling, a longer recall period was associated with greater median differences in the symptom onset time (b = 13.2, P = .023).

Conclusion

These results suggest that the time of symptom onset obtained at the time of the index event and documented in the MR is not interchangeable with data obtained later by research staff, especially if the interview is not conducted near the time of the index event.

Soybean (Glycine max L. Mer.), like many cultivated crops, has a relatively narrow genetic base and lacks diversity for some economically important traits. Glycine latifolia (Benth.) Newell & Hymowitz, one of the 26 perennial wild Glycine species related to soybean in the subgenus Glycine Willd., shows high levels of resistance to multiple soybean pathogens and pests including Alfalfa mosaic virus, Heterodera glycines Ichinohe and Sclerotinia sclerotiorum (Lib.) de Bary. However, limited information is available on the genomes of these perennial Glycine species. To generate molecular resources for gene mapping and identification, high-density linkage maps were constructed for G. latifolia using single nucleotide polymorphism (SNP) markers generated by genotyping by sequencing and evaluated in an F2 population and confirmed in an F5 population. In each population, greater than 2,300 SNP markers were selected for analysis and segregated to form 20 large linkage groups. Marker orders were similar in the F2 and F5 populations. The relationships between G. latifolia linkage groups and G. max and common bean (Phaseolus vulgaris L.) chromosomes were examined by aligning SNP-containing sequences from G. latifolia to the genome sequences of G. max and P. vulgaris. Twelve of the 20 G. latifolia linkage groups were nearly collinear with G. max chromosomes. The remaining eight G. latifolia linkage groups appeared to be products of multiple interchromosomal translocations relative to G. max. Large syntenic blocks also were observed between G. latifolia and P. vulgaris. These experiments are the first to compare genome organizations among annual and perennial Glycine species and common bean. The development of molecular resources for species closely related to G. max provides information into the evolution of genomes within the genus Glycine and tools to identify genes within perennial wild relatives of cultivated soybean that could be beneficial to soybean production.

Background

Children with Down syndrome (DS) are at increased risk of developing acute leukemia and are more prone to acute toxicities. We studied the incidence and severity of chronic health conditions among survivors of childhood leukemia with DS compared with those without DS.

Methods

Chronic health conditions reported by questionnaire were compared between 154 pediatric leukemia survivors with DS and 581 without DS, matched by leukemia, age at diagnosis, race/ethnicity, sex, radiation location and chemotherapy exposure using Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects were selected from 7139 5-year survivors of leukemia in the Childhood Cancer Survivor Study.

Results

Risk of at least 1 late onset chronic health condition (grade 1-5) was similar in the DS population compared with the non-DS group (HR, 1.1; 95% CI, 0.7-1.5). Serious chronic health conditions (grade 3-5) were more common in DS survivors (HR, 1.7; 95% CI, 1.1-2.6), as were ≥ 3 chronic health conditions (grades 1-5) (HR, 1.7; 95% CI, 1.2-2.4). The 25-year cumulative incidence of any condition (grades 1-5) was 83% for DS survivors and 69% for non-DS survivors.

Conclusion

Leukemia survivors with DS have therapy-related chronic health conditions comparable to those of similarly treated survivors without DS, with a few notable exceptions: 1) an increased risk of cataracts, hearing loss, and thyroid dysfunction compared with survivors without DS (though these are known risks in the DS population), 2) decreased risk of second cancers, and 3) increased risk of severe or multiple conditions. Practitioners should be aware of these risks during and after therapy. Cancer 2018;124:617-25. © 2017 American Cancer Society.

Aims

To identify women with diabetes at risk of increased postvoid residual volume (PVR) and investigate the relationship of increased PVR to urinary symptoms in women with diabetes.

Methods

PVR was measured by bladder ultrasonography in a cross-sectional cohort of 427 middle-aged and older women with diabetes. Participants completed questionnaires assessing urgency incontinence, stress incontinence, daytime frequency, nocturia, obstructive voiding, and diabetes-related end-organ complications: heart disease, stroke, neuropathy. Serum HbA1c and creatinine were recorded.

Results

75% of participants had a PVR of 0-49, 13% had a PVR of 50-99, and 12% had a PVR ≥ 100 mL. Approximately 59% of women with a PVR < 50 mL reported at least one lower urinary tract symptom. Women with diabetes and a PVR ≥ 100 mL were more likely to report urgency incontinence (OR 2.18, CI 1.08-4.41) and obstructive voiding symptoms (OR 2.47, CI 1.18-5.17) than women with PVR < 50 mL. In multivariable models, poorer glycemic control was associated with an increased likelihood of PVR ≥ 100 mL (OR 1.30, CI 1.06-1.59 per 1.0-U increase in HbA1c).

Conclusions

PVR volumes ≥ 100 mL may indicate increased risk of urgency incontinence and obstructive voiding. Glycemic control may play a role in preventing increased PVR in women with diabetes.

Objective

Contemporary models of trauma suggest that posttraumatic stress and growth should be related and that symptoms of stress resulting from a perceived trauma (e.g., childhood cancer) are prerequisite for posttraumatic growth (PTG) to occur. However, empirical data regarding the relationship of posttraumatic stress and growth have been equivocal. The purpose of this study is to examine the relationship between posttraumatic stress symptoms (PTSS) and PTG among adult survivors of childhood cancer.

Methods

Survey methods were used to collect data from 6,162 survivors participating in the Childhood Cancer Survivor Study (CCSS). Nonparametric correlation was examined pairwise between PTG and PTSS using Spearman's correlation coefficient with 95% confidence intervals, with nonlinear canonical correlation analysis being conducted to examine relationships between subscales. A multivariable partial proportional odds model was also fit for PTG total quartiles focusing on associations with PTSS total quartiles while adjusting for sociodemographic and medical variables.

Results

Examination of unadjusted PTSS and PTG total scores revealed a Spearman correlation of 0.11 (p < .001), with coefficients ranging from 0.03 to 0.17 between total and subscale scores. The nonlinear canonical correlation analyses resulted in two dimensions with eigenvalues of 0.15 and 0.14, resulting in a fit value of 0.30 and evidence that little variability in the data (15%) was explained by the weighted combinations of the variables.

Conclusions

Although statistically significant, these results do not indicate a robust relationship between PTSS and PTG among adult survivors of childhood cancer. Theories suggesting that PTSS is a prerequisite for PTG should be reconsidered.

Medication adherence improves outcomes for patients with heart failure, but adherence rates remain low. We examined the association between earlier postdischarge follow-up and medication adherence. We performed a retrospective cohort study of patients ≥65 years who were hospitalized for heart failure, covered by Medicare Part D, and discharged alive from April 2006 to October 2012 using the Get With The Guidelines-Heart Failure Registry linked to Medicare claims. Patients were categorized into 4 groups by timing of first postdischarge follow-up visit: ≤1, 1 to 2, 2 to 6, and >6 weeks. Medication adherence was defined by proportion of days covered of >80% at 90 days and 1-year posthospital discharge to 5 guideline-directed medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, evidence-based β-blocker, aldosterone antagonist, hydralazine/isosorbide dinitrate, and anticoagulation for atrial fibrillation). Among 9878 patients with heart failure, 73% had left ventricular ejection fraction ≤40%, median age was 78 years (25th-75th percentile, 71-84), and 48% were male. Overall, 30% had a follow-up appointment within 1-week postdischarge and 25% >6 weeks. At 1 year, medication adherence was 53% for evidence-based β-blockers, 48% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 8% for hydralazine/isosorbide dinitrate. We found no significant association between timing of first follow-up visit and medication adherence at 1 year (1.04, 0.92-1.17) when comparing follow-up visits >6 weeks to the earliest ones. Posthospital heart failure discharge, overall adherence to medical therapies in Medicare beneficiaries was low. Early follow-up was not associated with increased medication adherence to guideline-directed medical therapy in the short or long term.

Children with solid tumors, most of which are malignant, have an excellent prognosis when treated on contemporary regimens. These regimens, which incorporate chemotherapeutic agents and treatment modalities used for many decades, have evolved to improve relapse-free survival and reduce long-term toxicity. This review discusses the evolution of the treatment regimens employed for management of the most common solid tumors, emphasizing the similarities between contemporary and historical regimens. These similarities allow the use of historical patient cohorts to identify the late effects of successful therapy and to evaluate remedial interventions for these adverse effects.