INTEGRATING CLINICAL LABORATORY MEASURES AND ICD-9 CODE DIAGNOSES IN PHENOME-WIDE ASSOCIATION STUDIES.

Electronic health records (EHR) provide a comprehensive resource for discovery, allowing unprecedented exploration of the impact of genetic architecture on health and disease. The data of EHRs also allow for exploration of the complex interactions between health measures across health and disease. The discoveries arising from EHR based research provide important information for the identification of genetic variation for clinical decision-making.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

Importance: Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants.

Objective: To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes.

The IGNITE network: a model for genomic medicine implementation and research.

Background: Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility.

Methods: To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.

Comprehensive Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Evaluation of Once-Daily Efavirenz 400 and 600 mg in Treatment-Naïve HIV-Infected Patients at 96 Weeks: Results of the ENCORE1 Study.

Background: ENCORE1 demonstrated non-inferiority of daily efavirenz 400 mg (EFV400) versus 600 mg (EFV600) to 96 weeks in treatment-naïve, HIV-infected adults but concerns regarding lower EFV400 concentrations remained. Therefore, relationships between EFV pharmacokinetics (PK) and key genetic polymorphisms with 96-week efficacy and safety were investigated.

Methods: Relationships between EFV PK parameters and single nucleotide polymorphisms (SNP; CYP2B6, CYP2A6, CYP3A4, NR1I3, NR1I2, ABCB1) with plasma HIV-RNA (pVL) <200 copies/mL and EFV discontinuation and adverse events at 96 weeks were explored.

Biochar from Pyrolysis of Biosolids for Nutrient Adsorption and Turfgrass Cultivation.

At water resource recovery facilities, nutrient removal is often required and energy recovery is an ever-increasing goal. Pyrolysis may be a sustainable process for handling wastewater biosolids because energy can be recovered in the py-gas and py-oil. Additionally, the biochar produced has value as a soil conditioner.

Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers.

The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain's prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability.

Utilising the native plasmid, pCA2.4, from the cyanobacterium Synechocystis sp. strain PCC6803 as a cloning site for enhanced product production.

Background: The use of photosynthetic autotrophs and in particular the model organism Synechocystis PCC6803 is receiving much attention for the production of sustainable biofuels and other economically useful products through metabolic engineering. Optimisation of metabolic-engineered organisms for high-level sustained production of product is a key element in the manipulation of this organism. A limitation to the utilisation of metabolically-engineered Synechocystis PCC6803 is the availability of strong controllable promoters and stable gene dosage methods for maximising gene expression and subsequent product formation following genetic manipulation.

Triclocarban Influences Antibiotic Resistance and Alters Anaerobic Digester Microbial Community Structure.

Triclocarban (TCC) is one of the most abundant organic micropollutants detected in biosolids. Lab-scale anaerobic digesters were amended with TCC at concentrations ranging from the background concentration of seed biosolids (30 mg/kg) to toxic concentrations of 850 mg/kg to determine the effect on methane production, relative abundance of antibiotic resistance genes, and microbial community structure. Additionally, the TCC addition rate was varied to determine the impacts of acclimation time.

Are there right hemisphere contributions to visually-guided movement? Manipulating left hand reaction time advantages in dextrals.

Many studies have argued for distinct but complementary contributions from each hemisphere in the control of movements to visual targets. Investigators have attempted to extend observations from patients with unilateral left- and right-hemisphere damage, to those using neurologically-intact participants, by assuming that each hand has privileged access to the contralateral hemisphere. Previous attempts to illustrate right hemispheric contributions to the control of aiming have focussed on increasing the spatial demands of an aiming task, to attenuate the typical right hand advantages, to try to enhance a left hand reaction time advantage in right-handed participants.

A Nondestructive Method to Distinguish the Internal Constituent Architecture of the Intervertebral Discs Using 9.4 Tesla Magnetic Resonance Imaging.

Study Design: An in vitro study of the intervertebral disc (IVD) structure using 9.4T magnetic resonance imaging (MRI).

Objective: Investigate the potential of ultrahigh-field strength MRI for higher quality 3-dimensional (3D) volumetric MRI datasets of the IVD to better distinguish structural details.

A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough.

Assessment of an automated surveillance system for detection of initial ventilator-associated events.

Surveillance for initial ventilator-associated events (VAEs) was automated and compared with nonautomated review of episodes of mechanical ventilation. Sensitivity, specificity, positive predictive value, and negative predictive value of automated surveillance were very high (>93%), and automated surveillance reduced the time spent on detection of VAEs by >90%.

Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.

Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment-naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.

Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study.

Background: The week 48 primary analysis of the ENCORE1 trial established the virological non-inferiority and safety of efavirenz 400 mg compared with the standard 600 mg dose, combined with tenofovir and emtricitabine, as first-line HIV therapy. This 96-week follow-up of the trial assesses the durability of efficacy and safety of this treatment over 96 weeks.

Methods: ENCORE1 was a double-blind, placebo-controlled, non-inferiority trial done at 38 clinical sites in 13 countries.

The impact of triclosan on the spread of antibiotic resistance in the environment.

Triclosan (TCS) is a commonly used antimicrobial agent that enters wastewater treatment plants (WWTPs) and the environment. An estimated 1.1 × 10(5) to 4.

Attentional asymmetries - cause or consequence of human right handedness?

It is well established that the vast majority of the population favors their right hand when performing complex manual tasks. However, the developmental and evolutionary underpinnings of human manual asymmetries remain contentious. One often overlooked suggestion is that right handedness may stem from an asymmetrical bias in attention, with the right hand being allocated more attentional resources during bimanual tasks than the left hand (Peters, 1981).

Generality and specificity in the effects of musical expertise on perception and cognition.

Performing musicians invest thousands of hours becoming experts in a range of perceptual, attentional, and cognitive skills. The duration and intensity of musicians' training - far greater than that of most educational or rehabilitation programs - provides a useful model to test the extent to which skills acquired in one particular context (music) generalize to different domains. Here, we asked whether the instrument-specific and more instrument-general skills acquired during professional violinists' and pianists' training would generalize to superior performance on a wide range of analogous (largely non-musical) skills, when compared to closely matched non-musicians.

Contrasting Association Results between Existing PheWAS Phenotype Definition Methods and Five Validated Electronic Phenotypes.

Phenome-Wide Association Studies (PheWAS) comprehensively investigate the association between genetic variation and a wide array of outcome traits. Electronic health record (EHR) based PheWAS uses various abstractions of International Classification of Diseases, Ninth Revision (ICD-9) codes to identify case/control status for diagnoses that are used as the phenotypic variables. However, there have not been comparisons within a PheWAS between results from high quality derived phenotypes and high-throughput but potentially inaccurate use of ICD-9 codes for case/control definition.

Population risk factor estimates for abdominal aortic aneurysm from electronic medical records: a case control study.

Background: Using abdominal aortic aneurysm (AAA) as a model, this case-control study used electronic medical record (EMR) data to assess known risk factors and identify new associations.

Methods: The study population consisted of cases with AAA (n =888) and controls (n =10,523) from the Geisinger Health System EMR in Central and Northeastern Pennsylvania. We extracted all clinical and diagnostic data for these patients from January 2004 to December 2009 from the EMR.

Increased traffic accident rates associated with shale gas drilling in Pennsylvania.

Objectives: We examined the association between shale gas drilling and motor vehicle accident rates in Pennsylvania.

Methods: Using publicly available data on all reported vehicle crashes in Pennsylvania, we compared accident rates in counties with and without shale gas drilling, in periods with and without intermittent drilling (using data from 2005 to 2012). Counties with drilling were matched to non-drilling counties with similar population and traffic in the pre-drilling period.

Auditory semantic processing in dichotic listening: effects of competing speech, ear of presentation, and sentential bias on N400s to spoken words in context.

The effects of ear of presentation and competing speech on N400s to spoken words in context were examined in a dichotic sentence priming paradigm. Auditory sentence contexts with a strong or weak semantic bias were presented in isolation to the right or left ear, or with a competing signal presented in the other ear at a SNR of -12 dB. Target words were congruent or incongruent with the sentence meaning.

Quantifying cerebral asymmetries for language in dextrals and adextrals with random-effects meta analysis.

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarized opinion on whether or not they are as lateralized as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined.

Efavirenz 400 mg daily remains non-inferior to 600 mg: 96 week data from the double-blind, placebo-controlled ENCORE1 study.

Introduction: ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV) with tenofovir/emtricitabine (TDF/FTC) as first-line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non-inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety.

Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity.

Rationale: Dopamine β-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine in the central nervous system and peripherally. DBH variants are associated with large changes in circulating DBH and implicated in multiple disorders; yet causal relationships and tissue-specific effects remain unresolved.

Objective: To characterize regulatory variants in DBH, effect on mRNA expression, and role in modulating sympathetic tone and disease risk.