Numerical investigation of air intrusion and aerobic reactions in municipal solid waste landfills.

Air intrusion into municipal solid waste landfills can cause a localized switch from anaerobic to aerobic biodegradation adjacent to the intrusion. The purpose of this study was to explore the effects on temperature and gas composition of air intrusion into an idealized anaerobic landfill. Two scenarios of air intrusion and injection were simulated using a mechanistic landfill model built into TOUGH2.

Bacteria and Antibiotics in Wound Healing.

This review of the literature concerning bacteria, antibiotics and tissue repair shows there are extensive data supporting microbial interference with wound healing once bacterial burden exceeds 104 CFU per unit of measure, The mechanism of bacterial interference lies largely in prolonging the inflammatory phase of tissue repair. Reducing the microbial bioburden allows tissue repair to continue. Systemic and topical antimicrobials appear critical to reducing the bioburden and facilitating repair.

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data.

Modeling methane oxidation in landfill cover soils as indicator of functional stability with respect to gas management.

A performance-based method for evaluating methane (CH) oxidation as the best available control technology (BACT) for passive management of landfill gas (LFG) was applied at a municipal solid waste (MSW) landfill in central Washington, USA, to predict when conditions for functional stability with respect to LFG management would be expected. The permitted final cover design at the subject landfill is an all-soil evapotranspirative (ET) cover system. Using a model, a correlation between CH loading flux and oxidation was developed for the specific ET cover design.

Using Machine Learning Algorithms to Predict Risk for Development of Calciphylaxis in Patients with Chronic Kidney Disease.

Calciphylaxis is a disorder that results in necrotic cutaneous lesions with a high rate of mortality. Due to its rarity and complexity, the risk factors for and the disease mechanism of calciphylaxis are not fully understood. This work focuses on the use of machine learning to both predict disease risk and model the contributing factors learned from an electronic health record data set.

Case study comparison of functional vs. organic stability approaches for assessing threat potential at closed landfills in the USA.

Municipal solid waste (MSW) landfills in the USA are regulated under Subtitle D of the Resource Conservation and Recovery Act (RCRA), which includes the requirement to protect human health and the environment (HHE) during the post-closure care (PCC) period. Several approaches have been published for assessment of potential threats to HHE. These approaches can be broadly divided into organic stabilization, which establishes an inert waste mass as the ultimate objective, and functional stability, which considers long-term emissions in the context of minimizing threats to HHE in the absence of active controls.

Relational machine learning for electronic health record-driven phenotyping.

Objective: Electronic health records (EHR) offer medical and pharmacogenomics research unprecedented opportunities to identify and classify patients at risk. EHRs are collections of highly inter-dependent records that include biological, anatomical, physiological, and behavioral observations. They comprise a patient's clinical phenome, where each patient has thousands of date-stamped records distributed across many relational tables.

Longitudinal data analysis in support of functional stability concepts for leachate management at closed municipal landfills.

Landfill functional stability provides a target that supports no environmental threat at the relevant point of exposure in the absence of active control systems. With respect to leachate management, this study investigates "gateway" indicators for functional stability in terms of the predictability of leachate characteristics, and thus potential threat to water quality posed by leachate emissions. Historical studies conducted on changes in municipal solid waste (MSW) leachate concentrations over time (longitudinal analysis) have concentrated on indicator compounds, primarily chemical oxygen demand (COD) and biochemical oxygen demand (BOD).

SNPs previously associated with Dupuytren's disease replicated in a North American cohort.

Objective: Dupuytren's disease is a progressive fibrosis of the hand that often results in debilitating flexion contractures. Its etiology is not completely understood but likely involves both genetic and environmental factors. A recent study performed in Europe identified DNA variants that associate with Dupuytren's disease.

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

Background: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.

Methods: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy.

Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial.

Background: Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin.

Evaluation of a mitochondrial DNA mutation in maternally inherited and sporadic cases of Dupuytren disease.

Objective: The purpose was to test the hypothesis that Dupuytren disease (DD) is associated with a previously reported mutation in mitochondrial DNA at position 2839.

Methods: Two hundred sixty-nine cases of DD and an equal number of matched controls were identified in Marshfield Clinic's Personalized Medicine Research Project (PMRP). Clinical data used to describe the cohort were abstracted from the electronic medical records of the population.

Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy.

By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation.

Absence of novel CYP4F2 and VKORC1 coding region DNA variants in patients requiring high warfarin doses.

Objective: Warfarin is an FDA-approved oral anticoagulant for long-term prevention of thromboembolism. Substantial inter-individual variation in dosing requirements and the narrow therapeutic index of this widely-prescribed drug make safe initiation and dose stabilization challenging. Single nucleotide polymorphisms (SNPs) occurring in CYP2C9, VKORC1, and CYP4F2 genes are known to impact dose, and VKORC1 and CYP4F2 polymorphisms are associated with higher therapeutic dose requirements in our cohort.

A randomized controlled trial of genotype-based Coumadin initiation.

Purpose: A randomized controlled trial was conducted in patients initiating warfarin to determine whether algorithms that incorporate genotypes affecting warfarin metabolism and function, and Vitamin K metabolism improve prediction of therapeutic warfarin dose and anticoagulation management.

Methods: A total of 230 patients were randomized to either a clinical arm where dosing algorithms considered only clinical information or an interventional arm where dosing algorithms used clinical and genotypic variables (CYP2C9, CYP4F2, and VKORC1). Subjects in the interventional arm were genotyped within 5 hours, and the initial dose was informed by genotype.

Wound surgery.

The purpose of this article is to review the concepts behind, and practice of, wound surgery. The techniques of wound surgery, born of necessity in the art of military surgeons, have found their renaissance in the modern age of wound care driven by the economic and functional considerations inherent to the outcome-based management of chronic disease. Over 300 years of literature on wound healing has shown an innate ability of the wound (in the absence of infection and repeated trauma) to control its progress, largely through the local inflammatory cells.

New adjuvants to enhance anticoagulant activity of warfarin.

New adjuvants of warfarin anticoagulant activity have been developed. These compounds, which are 1,4-methano-1,2,3,4-tetrahydroanthracene-9,10-diol derivatives, act synergistically with warfarin to potentiate its anticoagulant effect. None of the compounds tested is an effective oral anticoagulant in the absence of warfarin.

Perioperative genomic profiles using structure-specific oligonucleotide probes.

Objectives: Many complications in the perioperative interval are associated with genetic susceptibilities that may be unknown in advance of surgery and anesthesia, including drug toxicity and inefficacy, thrombosis, prolonged neuromuscular blockade, organ failure and sepsis. The aims of this study were to design and validate the first genetic testing platform and panel designed for use in perioperative care, to establish allele frequencies in a target population, and to determine the number of mutant alleles per patient undergoing surgery. DESIGN/SETTING/PARTICIPANTS AND METHODS: One hundred fifty patients at Marshfield Clinic, Marshfield, Wisconsin, 100 patients at the Medical College of Wisconsin Zablocki Veteran's Administration Medical Center, Milwaukee, Wisconsin, and 200 patients at the University of Wisconsin Hospitals and Clinics, Madison, Wisconsin undergoing surgery and anesthesia were tested for 48 polymorphisms in 22 genes including ABC, BChE, ACE, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, beta2AR, TPMT, F2, F5, F7, MTHFR, TNFalpha, TNFbeta, CCR5, ApoE, HBB, MYH7, ABO and Gender (PRKY, PFKFB1).

Understanding the pharmacogenetic approach to warfarin dosing.

Warfarin remains the drug of choice for long-term anticoagulation management in a variety of conditions. Despite an established role in prevention of thromboembolic events such as stroke, warfarin continues to be underutilized because of its association with serious drug-related adverse events. Lacking alternative therapeutic approaches, intensive research in the past decade has focused on making anticoagulation with warfarin safer.

The Marshfield Clinic Personalized Medicine Research Project: 2008 scientific update and lessons learned in the first 6 years.

The Marshfield Clinic Personalized Medicine Research Project is the largest population-based biobank in the USA, with the ability to recontact subjects to obtain additional information to facilitate gene-environment studies. Nearly 20,000 adults have enrolled in the Personalized Medicine Research Project since 2001, after providing active written consent to access their Marshfield Clinic medical records to define phenotype and providing blood samples from which DNA, plasma and serum samples were stored. Numerous studies are underway in the area of pharmacogenetics and genetic epidemiology.

CYP4F2 genetic variant alters required warfarin dose.

Warfarin is an effective, commonly prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of drug-associated adverse events, warfarin remains underprescribed. Further, interindividual variability in therapeutic dose mandates frequent monitoring until target anticoagulation is achieved.

Evaluation of genetic factors for warfarin dose prediction.

Objectives: Warfarin is a commonly prescribed anticoagulant drug used to prevent thromboses that may arise as a consequence of orthopedic and vascular surgery or underlying cardiovascular disease. Warfarin is associated with a notoriously narrow therapeutic window where small variations in dosing may result in hemorrhagic or thrombotic complications. To ultimately improve dosing of warfarin, we evaluated models for stable maintenance dose that incorporated both clinical and genetic factors.