Leveraging eco-evolutionary models for gene drive risk assessment

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives. Supplemental files attached belo

Beneficial Reuse and Sustainability: The Fate of Organic Compounds in the Land-Applied Waste

Land application systems, also referred to as beneficial reuse systems, are engineered systems that have defined and permitted application areas based on site and waste characteristics to determine the land area size requirement. These terrestrial systems have orders of magnitude greater microbial capability and residence time to achieve decomposition and assimilation compared with aquatic systems. In this paper we focus on current information and information needs related to terrestrial fate pathways in land treatment systems. Attention is given to conventional organic chemicals as well as new estrogenic and pharmaceutical chemicals of commerce. Specific terrestrial fate pathways addressed include: decomposition, bound residue formation, leaching, runoff, and crop uptake. Molecular decomposition and formation of bound residues provide the basis for the design and regulation of land treatment systems. These mechanisms allow for assimilation of wastes and nondegradation of the environment and accomplish the goal of sustainable land use. Bound residues that are biologically produced are relatively immobile, degrade at rates similar to natural soil materials, and should present a significantly reduced risk to the environment as opposed to parent contaminants. With regard to leaching and runoff pathways, no comprehensive summary or mathematical model of organic chemical migration from land treatment systems has been developed. For the crop uptake pathway, a critical need exists to develop information for nonagricultural chemicals and to address full-scale performance and monitoring at more land application sites. The limited technology choices for treatment of biosolids, liquids, and other wastes implies that acceptance of some risks and occurrence of some benefits will continue to characterize land application practices that contribute directly to the goal of beneficial reuse and sustainability

NbSe3: Effect of Uniaxial Stress on the Threshold Field and Fermiology

We have measured the effect of uniaxial stress on the threshold field ET for the motion of the upper CDW in NbSe3. ET exhibits a critical behavior, ET ~ (1 - e/ec)^g, wher e is the strain, and ec is about 2.6% and g ~ 1.2. This ecpression remains valid over more than two decades of ET, up to the highest fields of about 1.5keV/m. Neither g nor ec is very sensitive to the impurity concentraction. The CDW transition temperature Tp decreases linearly with e at a rate dTp/de = -10K/%, and it does not show any anomaly near ec. Shubnikov de-Haas measurements show that the extremal area of the Fermi surface decreases with increasing strain. The results suggest that there is an intimate relationship between pinning of the upper CDW and the Fermiology of NbSe3.Comment: 4 pages, 5 figure

Associations Between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress

Law professors want hearing, vote on Garland

Dear Senator Fischer and Senator Sasse, We write this as citizens, but we all teach at the University of Nebraska College of Law. We hold different political viewpoints and disagree frequentIy with each other on political and legal issues. As law professors, however, we share a deep commitment to the rule of law and an impartial judiciary. We therefore urge you to hold confirmation hearings and a vote on President Obama\u27s Supreme Court nominee, Chief Judge Merrick B. Garland

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BACKGROUND: Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. METHODS: This observational, prospective surveillance study recruited hospitalized adults aged \u3e /=18years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. RESULTS: Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1years and 52.7% were aged \u3e /=65years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged \u3e /=65years. Among patients aged 18-64years PCV13 serotypes were detected in 3.8-5.3% of patients depending on their risk status. CONCLUSIONS: After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population

Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

<p>Abstract</p> <p>Background</p> <p>Cancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients.</p> <p>Methods/Design</p> <p>This study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale), a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline). As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden.</p> <p>Discussion</p> <p>This extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment), ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.</p

PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer

IntroductionAlthough most invasive cervical cancer (ICC) harbor 30years further strengthened these associations.ConclusionsWhile the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk