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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.

AimsTo estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress.DesignRetrospective cohort study with longitudinal follow-up of self-reported health outcomes.SettingChildhood Cancer Survivor Study (CCSS), a 26-center study of ≥ 5-year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada.ParticipantsA total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress.MeasurementsSurvivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory-18 and the Posttraumatic Stress Diagnostic Scale.FindingsAfter adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1-1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1-1.5), anxiety (RR = 1.6; 95% CI = 1.3-2.1), and somatization (RR = 1.2; 95% CI = 1.1-1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4-2.3).ConclusionsDrinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.

Background Neurocognitive impairments are sequelae of childhood cancer treatment, however little guidance is given to clinicians on common phenotypes of impairment or modifiable risk factors that could lead to personalized interventions in survivorship. Methods Standardized clinical testing of neurocognitive function was conducted in 2958 (74.1%) eligible survivors, who were at least 5 years postdiagnosis and aged older than 18 years, and 477 community controls. Impairment was examined across 20 measures, and phenotypes were determined by latent class analysis. Multinomial logistic regression was used to estimate risk for phenotype, predicted by cancer diagnosis and treatment exposures, chronic health conditions, and lifestyle, adjusted for sex and age. Associations between phenotypes and social attainment were examined. Results Five neurocognitive phenotypes were identified in survivors (global impairment 3.7%, impaired attention 5.0%, memory impairment 7.2%, processing speed and executive function impairment 9.3%, no impairment 74.8%). Risk of global impairment was associated with severe chronic health condition burden (odds ratio [OR] = 20.17, 95% confidence interval [CI] = 11.41 to 35.63) including cerebrovascular disease (OR = 14.5, 95% CI = 5.47 to 38.44) and cerebrovascular accident (OR = 14.7, 95% CI = 7.50 to 26.40). Modifiable risk factors, such as quitting smoking, reduced risk for global impairment (OR = 0.21, 95% CI = 0.06 to 0.66). Low physical activity increased risk for global impairment (OR = 4.54, 95% CI = 2.86 to 7.21), attention impairment (OR = 2.01, 95% CI = 1.41 to 2.87), processing speed and executive function impairment (OR = 1.90, 95% CI = 1.46 to 2.48), and memory impairment (OR = 2.09, 95% CI = 1.54 to 2.82). Conclusions Results support the clinical utility of neurocognitive phenotyping to develop risk profiles and personalized clinical interventions, such as preventing cerebrovascular disease in anthracycline-treated survivors by preventing hypercholesterolemia, smoking, and sedentary lifestyle, to reduce the risk for global impairment. [ABSTRACT FROM AUTHOR]

Background: Subsequent short‐latency leukemias are well‐described among survivors of childhood cancer. However, late (5–14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort. Methods: Subsequent leukemias, among 25,656 five‐year survivors, were self‐reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures. Results: Seventy‐seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 years, range 5.0–14.5 years) and 28 with VLL (median time from diagnosis 25.4 years, range 15.9–42.8 years), with a cumulative incidence of 0.23% (95% CI 0.18%–0.30%) 20 years from diagnosis for all subsequent leukemias. The most common leukemia subtypes were acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. Compared to the general population, survivors were at increased risk, for developing LL (SIR 9.3, 95% CI 7.0–12.1) and VLL (SIR 5.9, 95% CI 3.9–8.4). In multivariable relative risk analyses, cumulative epipodophyllotoxin dose >4000 mg/m2 was associated with increased risk for LL and VLL (RR 4.5, 95% CI 2.0–9.9). Conclusions: In this large series of late subsequent leukemias, survivors of childhood cancer are at increased risk, with no evidence of plateau over time. We observed most risk among survivors who received high cumulative doses of epipodophyllotoxins. Ongoing consideration for this late effect should continue beyond 10 years. [ABSTRACT FROM AUTHOR]

Perinatal HIV infection is associated with delayed neurocognitive development, but less is known about children perinatally HIV-exposed but uninfected (CHEU). We compared cognitive and language outcomes in 4-6-year old CHEU versus children HIV-unexposed and uninfected (CHUU) and children living with HIV (CLHIV). We enrolled 1,581 children (77% of the child population) in five communities in KwaZulu-Natal, South Africa. Children completed: Grover-Counter Scale of cognitive development, sub-scales of the Kaufman Assessment Battery for Children, Reynell Developmental Language Scales. HIV status of children and primary caregivers was determined by repeated rapid tests or report of prior testing. We conducted a cross-sectional multivariable linear regression on 922 dyads with complete data (257 CHEU, 627 CHUU, 38 CLHIV). On all outcome measures, CHEU and CHUU groups had comparable scores; CLHIV scored significantly lower. Emerging global progress toward the elimination of vertical HIV transmission may not only reduce mortality, but also positively impact child development.

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.

BackgroundChildren 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.MethodsChronic 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.ResultsRisk 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.ConclusionLeukemia 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.