Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.

Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d.

Inflated expectations: Rare-variant association analysis using public controls.

The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.

Invasive Urban Mammalian Predators: Distribution and Multi-Scale Habitat Selection.

A barrier to successful ecological restoration of urban green spaces in many cities is invasive mammalian predators. We determined the fine- and landscape-scale habitat characteristics associated with the presence of five urban predators (black and brown rats, European hedgehogs, house mice, and brushtail possums) in three New Zealand cities, in spring and autumn, in three green space types: forest fragments, amenity parks, and residential gardens. Season contributed to variations in detections for all five taxa.

Detection parameters for managing invasive rats in urban environments.

Effective mitigation of the impacts of invasive ship rats (Rattus rattus) requires a good understanding of their ecology, but this knowledge is very sparse for urban and peri-urban areas. We radiomarked ship rats in Wellington, New Zealand, to estimate detection parameters (σ, ε, θ, and g) that describe the process of an animal encountering a device (bait stations, chew cards and WaxTags) from a distance, and then approaching it and deciding whether to interact with it. We used this information in simulation models to estimate optimal device spacing for eradicating ship rats from Wellington, and for confirming eradication.

Extreme Precipitation and Flooding Contribute to Sudden Vegetation Dieback in a Coastal Salt Marsh.

Climate extremes are becoming more frequent with global climate change and have the potential to cause major ecological regime shifts. Along the northern Gulf of Mexico, a coastal wetland in Texas suffered sudden vegetation dieback following an extreme precipitation and flooding event associated with Hurricane Harvey in 2017. Historical salt marsh dieback events have been linked to climate extremes, such as extreme drought.

Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in the Childhood Cancer Survivor Study.

Background: Pediatric cancers are the leading cause of death by disease in children despite improved survival rates overall. The contribution of germline genetic susceptibility to pediatric cancer survivors has not been extensively characterized. We assessed the frequency of pathogenic or likely pathogenic (P/LP) variants in 5451 long-term pediatric cancer survivors from the Childhood Cancer Survivor Study.

Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair.

In-utero exposure to zidovudine-containing antiretroviral therapy and clonal hematopoiesis in HIV-exposed uninfected newborns.

Objective: Zidovudine (ZDV) has been extensively used in pregnant women to prevent vertical transmission of HIV but few studies have evaluated potential mutagenic effects of ZDV during fetal development.

Design: Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were ZDV-exposed and 91 antiretroviral therapy (ART)-unexposed and matched for potential confounding factors.

Methods: Utilizing high depth sequencing and genotyping arrays, we comprehensively examined blood samples collected during the first week after birth for potential clonal hematopoiesis associated with fetal ZDV exposure, including clonal single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural copy number or copy neutral alterations.

Subsequent Neoplasm Risk Associated With Rare Variants in DNA Damage Response and Clinical Radiation Sensitivity Syndrome Genes in the Childhood Cancer Survivor Study.

Purpose: Radiotherapy for childhood cancer is associated with elevated subsequent neoplasm (SN) risk, but the contribution of rare variants in DNA damage response and radiation sensitivity genes to SN risk is unknown.

Patients And Methods: We conducted whole-exome sequencing in a cohort of childhood cancer survivors originally diagnosed during 1970 to 1986 (mean follow-up, 32.7 years), with reconstruction of doses to body regions from radiotherapy records.

Responses of New Zealand forest birds to management of introduced mammals.

Over the past 1000 years New Zealand has lost 40-50% of its bird species, and over half of these extinctions are attributable to predation by introduced mammals. Populations of many extant forest bird species continue to be depredated by mammals, especially rats, possums, and mustelids. The management history of New Zealand's forests over the past 50 years presents a unique opportunity because a varied program of mammalian predator control has created a replicated management experiment.

Quantifying hydrologic controls on local- and landscape-scale indicators of coastal wetland loss.

Background And Aims: Coastal wetlands have evolved to withstand stressful abiotic conditions through the maintenance of hydrologic feedbacks between vegetation production and flooding. However, disruption of these feedbacks can lead to ecosystem collapse, or a regime shift from vegetated wetland to open water. To prevent the loss of critical coastal wetland habitat, we must improve understanding of the abiotic-biotic linkages among flooding and wetland stability.

Behaviourally specialized foragers are less efficient and live shorter lives than generalists in wasp colonies.

A widely held assumption in ecology is that specialists are more efficient than generalists. However, empirical evidence for this fundamental assumption is surprisingly scarce and often contradictory. Theoretically, the evolution of alternative life history strategies is underpinned by a trade-off between activity levels and survival.

The Impact of a Heart Failure Management Program in a Medicare Advantage Population.

Heart failure (HF) is currently among the most prevalent and costly chronic diseases among older adults, who are at increased risk because of other chronic conditions and the aging process. HF has a significant impact on the health care system, patient outcomes, and the unsustainable rising costs of care. The primary objectives were to: (1) determine cost savings differences in medical expenditures between engaged and non-engaged members referred to a HF management program; (2) examine differences in length of stay and time to first post-engagement acute inpatient admission; and (3) examine the impact of using a remote weight monitoring scale on medical expenditures and inpatient admissions.

Climate and plant controls on soil organic matter in coastal wetlands.

Coastal wetlands are among the most productive and carbon-rich ecosystems on Earth. Long-term carbon storage in coastal wetlands occurs primarily belowground as soil organic matter (SOM). In addition to serving as a carbon sink, SOM influences wetland ecosystem structure, function, and stability.

Alternative Isoform Analysis of Ttc8 Expression in the Rat Pineal Gland Using a Multi-Platform Sequencing Approach Reveals Neural Regulation.

Alternative isoform regulation (AIR) vastly increases transcriptome diversity and plays an important role in numerous biological processes and pathologies. However, the detection and analysis of isoform-level differential regulation is difficult, particularly in the face of complex and incompletely-annotated transcriptomes. Here we have used Illumina short-read/high-throughput RNA-Seq to identify 55 genes that exhibit neurally-regulated AIR in the pineal gland, and then used two other complementary experimental platforms to further study and characterize the Ttc8 gene, which is involved in Bardet-Biedl syndrome and non-syndromic retinitis pigmentosa.

The Association Between Health Program Participation and Employee Retention.

Objective: Using health plan membership as a proxy for employee retention, the objective of this study was to examine whether use of health promotion programs was associated with employee retention.

Methods: Propensity score weighted generalized linear regression models were used to estimate the association between telephonic programs or health risk surveys and retention. Analyses were conducted with six study samples based on type of program participation.

Detection and visualization of differential splicing in RNA-Seq data with JunctionSeq.

Although RNA-Seq data provide unprecedented isoform-level expression information, detection of alternative isoform regulation (AIR) remains difficult, particularly when working with an incomplete transcript annotation. We introduce JunctionSeq, a new method that builds on the statistical techniques used by the well-established DEXSeq package to detect differential usage of both exonic regions and splice junctions. In particular, JunctionSeq is capable of detecting differential usage of novel splice junctions without the need for an additional isoform assembly step, greatly improving performance when the available transcript annotation is flawed or incomplete.

Using Propensity to Succeed Modeling to Increase Utilization and Adherence in a Nurse HealthLine Telephone Triage Program.

Propensity to succeed modeling was used to identify characteristics associated with higher utilization of a telephone triage program and adherence to nurse recommendations among callers. Characteristics significantly associated with calling the telephone triage service and engaging in triage services were being female and having an elevated health risk score. Callers most likely to adhere to nurse recommendations were younger than 85 years of age, had called on a weekday, and had received a recommendation to seek care at an emergency department or a doctor's office visit.

Frequency of Participation in an Employee Fitness Program and Health Care Expenditures.

Regular physical activity is strongly linked to prevention of costly chronic health conditions. However, there has been limited examination of the impact that level of participation in physical activity promotion programs has on health care costs. This study examined a fitness reimbursement program (FRP) offered to small employers.

Association Between Corporate Wellness Program Participation and Changes in Health Risks.

Objective: To assess the relationship between wellness program participation and employee health risks.

Methods: Data from 173,901 health-risk appraisals and wellness program participation records were used to assess changes in seven health risks (blood pressure, body weight, cholesterol level, nutrition, physical inactivity, stress, and tobacco use).

Results: Controlling for baseline covariates, high-risk members who completed only a coaching program were significantly more likely to lower five out of seven health risks than were high-risk members in the comparison group.

Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome.

The term neurotranscriptomics is used here to describe genome-wide analysis of neural control of transcriptomes. In this report, next-generation RNA sequencing was using to analyze the effects of neonatal (5-days-of-age) surgical stimulus deprivation on the adult rat pineal transcriptome. In intact animals, more than 3000 coding genes were found to exhibit differential expression (adjusted-p < 0.

QoRTs: a comprehensive toolset for quality control and data processing of RNA-Seq experiments.

Background: High-throughput next-generation RNA sequencing has matured into a viable and powerful method for detecting variations in transcript expression and regulation. Proactive quality control is of critical importance as unanticipated biases, artifacts, or errors can potentially drive false associations and lead to flawed results.

Results: We have developed the Quality of RNA-Seq Toolset, or QoRTs, a comprehensive, multifunction toolset that assists in quality control and data processing of high-throughput RNA sequencing data.

DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3'-end GC density.

Diminished ovarian function occurs early and is a primary cause for age-related decline in female fertility; however, its underlying mechanism remains unclear. This study investigated the roles that genome and epigenome structure play in age-related changes in gene expression and ovarian function, using human ovarian granulosa cells as an experimental system. DNA methylomes were compared between two groups of women with distinct age-related differences in ovarian functions, using both Methylated DNA Capture followed by Next Generation Sequencing (MethylCap-seq) and Reduced Representation Bisulfite Sequencing (RRBS); their transcriptomes were investigated using mRNA-seq.

Weaker resource diffusion effect at coarser spatial scales observed for egg distribution of cabbage white butterflies.

Mobile organisms frequently forage for patchy resources; e.g. herbivorous insects searching for host plants.