Forensic odontology in disaster victim identification.

This paper reviews MFI's from a historical perspective commencing with DVI in the late 20th century. For this paper, this era, 1970-90s is designated as the early modern period. As DVI by DNA analysis is introduced into the process, in the beginning of the mid-1990s, or late modern period, a shift in ID modality usage is noted.

Linking Endogenous Factor Xa Activity, a Biologically Relevant Pharmacodynamic Marker, to Edoxaban Plasma Concentrations and Clinical Outcomes in the ENGAGE AF-TIMI 48 Trial.

Background: We previously reported exogenous antifactor Xa (FXa) activity as a pharmacokinetic surrogate marker for edoxaban plasma concentrations. Inhibition of endogenous FXa activity is a more biologically relevant pharmacodynamic measure of edoxaban activity. Here we describe the value of endogenous FXa activity as a pharmacodynamic marker linking edoxaban concentrations and clinical outcomes in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48).

Healthy Lifestyle During Early Pregnancy and Risk of Gestational Diabetes Mellitus.

Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4).

Maternal healthy lifestyle during early pregnancy and offspring birthweight: differences by offspring sex.

Purpose: Individual maternal lifestyle factors during pregnancy have been associated with offspring birthweight; however, associations of combined lifestyle factors with birthweight and potential differences by offspring sex have not been examined.

Materials And Methods: Participants (N = 2924) were identified from a pregnancy cohort in Washington state. Lifestyle factors during early pregnancy were dichotomized based on Alternate Healthy Eating Index score ≥62, leisure time physical activity (LTPA) ≥ 150 min/week, not smoking during pregnancy and Perceived Stress Scale score ≤3, then combined into a lifestyle score (0-4).

Population Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial.

Introduction: Edoxaban is a novel factor Xa inhibitor. This study characterizes the population pharmacokinetics of edoxaban in patients with non-valvular atrial fibrillation (NVAF) included in the phase III ENGAGE AF-TIMI 48 study, evaluates covariates for the dose-exposure relationship in this population, and assesses the impact of protocol-specified dose reductions on exposure using simulations.

Methods: Model development was performed using NONMEM(®) and based on sparse data from the ENGAGE AF-TIMI 48 study augmented with dense data from 13 phase I studies to inform and stabilize the model.

Maternal Leisure Time Physical Activity and Infant Birth Size.

Background: Associations of maternal leisure time physical activity with birth size are inconsistent. Roles of infant sex and maternal prepregnancy body mass index (BMI) in these associations have not been studied.

Methods: Participants (N = 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported leisure time physical activity duration and energy expenditure in the year prepregnancy and in early pregnancy (mean 15 weeks gestation).

Population pharmacokinetics of edoxaban in patients with symptomatic deep-vein thrombosis and/or pulmonary embolism--the Hokusai-VTE phase 3 study.

Aims: This study characterized the population pharmacokinetics of edoxaban in patients with symptomatic deep-vein thrombosis and/or pulmonary embolism in the Hokusai-VTE phase 3 study. The impact of the protocol-specified 50% dose reductions applied to patients with body weight ≤ 60 kg, creatinine clearance (CL(cr)) of 30 to 50 ml min(-1) or concomitant P-glycoprotein inhibitor on edoxaban exposure was assessed using simulations.

Methods: The sparse data from Hokusai-VTE, 9531 concentrations collected from 3707 patients, were pooled with data from 13 phase 1 studies.

Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin.

A population pharmacokinetic model was developed to describe plasma concentrations of mirogabalin and lactam metabolite, obtained following a single oral dose of 5 mg mirogabalin to subjects with varying degrees of renal function.A 2-compartment model was used for both mirogabalin and lactam metabolite. Body weight was a significant covariate on volume of distribution of mirogabalin and lactam metabolite, whereas creatinine clearance significantly affected both renal and nonrenal clearance of mirogabalin.

Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain.

Mirogabalin (DS-5565) is an α2δ-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Nonlinear mixed-effects analyses were performed on average daily pain and on the incidence of the adverse events dizziness and somnolence. These models were used to predict the dose of mirogabalin equivalent to pregabalin and the probability of meaningful reduction in pain compared with placebo and pregabalin.

Population pharmacokinetics of edoxaban and its main metabolite in a dedicated renal impairment study.

A model characterizing the population pharmacokinetics (PK) of edoxaban and its major metabolite, M4, following a single oral dose of 15 mg administered to subjects with varying kidney function was developed. Thirty-two subjects contributed with edoxaban plasma, edoxaban urine, and M4 plasma concentrations. Edoxaban urine concentrations allowed estimation of renal clearance, and high contribution of renal to total clearance enabled estimation of absolute oral bioavailability.

Population pharmacokinetics and dose-exposure proportionality of edoxaban in healthy volunteers.

Background And Objectives: Edoxaban is a novel direct inhibitor of activated factor Xa. A previous human pharmacokinetic study suggested a less than proportional increase in edoxaban exposure at higher dose concentrations, but the quantitative relationship, including the point of inflection, has not yet been fully characterized. The objectives of this analysis were to characterize the population pharmacokinetics and quantify the dose-exposure relationship of edoxaban over a dose range of 10-180 mg.

Edoxaban population pharmacokinetics and exposure-response analysis in patients with non-valvular atrial fibrillation.

Purpose: The aim of this study was to evaluate the population pharmacokinetics (PK) and exposure-response relationship of edoxaban in patients with non-valvular atrial fibrillation (AF).

Methods: Concentration data from 1,134 subjects in 11 clinical studies (eight phase I, one phase II, and two phase III) were used to perform a population PK analysis, including estimation of the bioavailability and quantification of the effects of P-glycoprotein (P-gp) inhibitors as well as renal impairment on edoxaban PK. The potential relationship between edoxaban PK exposure and incidence of bleeding events was explored based on data from 893 AF patients.

Association of serum vitamin D with symptoms of depression and anxiety in early pregnancy.

Unlabelled: Abstract Objective: To evaluate associations between early pregnancy 25-hydroxyvitamin D (25[OH]D) concentrations and antepartum depression and anxiety symptoms and potential modifiers thereof.

Materials And Methods: In a pregnancy cohort (N=498), we examined cross-sectional associations of early pregnancy (mean=15.4 weeks gestation) serum 25[OH]D concentrations and depression and anxiety symptoms.

The association of maternal adult weight trajectory with preeclampsia and gestational diabetes mellitus.

Background: Preeclampsia (PE) and gestational diabetes mellitus (GDM) adversely affect pregnancy outcomes and the subsequent health of both mother and infant. It is known that elevated pre-pregnancy body mass index (BMI) is associated with increased risk of these obstetrical complications. However, little is known about the role of adult weight patterns prior to pregnancy.

Population pharmacokinetic-pharmacodynamic modeling analysis of intrinsic FXa and bleeding from edoxaban treatment.

Edoxaban is an oral, once-daily, direct factor Xa (FXa) inhibitor that has been evaluated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of venous thromboembolism (VTE) recurrence. Pharmacokinetic (PK) and pharmacodynamic (PD) modeling and logistic regression analyses were used to explore the clinical data from phase 1 and 2 studies to determine the relationship among PK exposure, PD response, and bleeding risk. Population PK/PD modeling was performed using plasma edoxaban concentration data from combined phase 1 and 2 studies and using intrinsic FXa data from a phase 2 AF study.

NMR-based metabolomic investigation of bioactivity of chemical constituents in black raspberry (Rubus occidentalis L.) fruit extracts.

Black raspberry (Rubus occidentalis L.) (BR) fruit extracts with differing compound profiles have shown variable antiproliferative activities against HT-29 colon cancer cell lines. This study used partial least-squares (PLS) regression analysis to develop a high-resolution (1)H NMR-based multivariate statistical model for discerning the biological activity of BR constituents.

Priming effects in boreal black spruce forest soils: quantitative evaluation and sensitivity analysis.

Laboratory studies show that introduction of fresh and easily decomposable organic carbon (OC) into soil-water systems can stimulate the decomposition of soil OC (SOC) via priming effects in temperate forests, shrublands, grasslands, and agro-ecosystems. However, priming effects are still not well understood in the field setting for temperate ecosystems and virtually nothing is known about priming effects (e.g.

Maternal birthweight is associated with subsequent risk of vitamin D deficiency in early pregnancy.

Background: Maternal low birthweight and vitamin D deficiency in pregnancy are associated with a similar spectrum of adverse pregnancy outcomes including pre-eclampsia and gestational diabetes. However, the relationship between maternal birthweight and subsequent vitamin D concentrations in early pregnancy is largely unknown.

Methods: We assessed whether self-reported maternal birthweight was associated with risk of early pregnancy vitamin D deficiency (≤20 ng/mL) among a pregnancy cohort (n = 658).

Model-Supported Development of CS-8635: A Fixed-Dose Combination of Olmesartan, Amlodipine, and Hydrochlorothiazide.

CS-8635, a fixed-dose triple combination of olmesartan, amlodipine, and hydrochlorothiazide, was developed to address the growing need for additional blood pressure (BP) reduction in patients not controlled with dual-combination therapies. Prior to Phase III, modeling and simulation (M&S) was conducted to estimate the additional BP lowering effect of CS-8635 compared to the respective dual combinations. The Phase III study evaluated CS-8635 BP lowering effects only at the highest dose strength among the five dose strengths to be developed.

Analysis of exposure-response of CI-945 in patients with epilepsy: application of novel mixed hidden Markov modeling methodology.

We propose to describe exposure-response relationship of an antiepileptic agent, using mixed hidden Markov modeling methodology, to reveal additional insights in the mode of the drug action which the novel approach offers. Daily seizure frequency data from six clinical studies including patients who received gabapentin were available for the analysis. In the model, seizure frequencies are governed by underlying unobserved disease activity states.

Age at menarche, menstrual characteristics, and risk of preeclampsia.

We examined associations of age at menarche and menstrual characteristics with the risk of preeclampsia among participants (n = 3,365) of a pregnancy cohort study. Data were collected using in-person interviews and medical record abstraction. Logistic regression was used to estimate adjusted odds ratio (OR) and 95% confidence interval (95% CI).

The crash of Colgan Air flight 3407: Advanced techniques in victim identification.

Background: Identifying disaster victims by means of dental records is a well-established technique. In cases in which high temperatures are involved, destruction of the structural relationship of the dentition necessitates that adjunctive aids be used in the identification process. Analysis of tooth fragments by means of scanning electron microscopy with energy dispersive x-ray spectroscopy can reveal evidence of restorative procedures, as well as trace amounts of dental materials remaining on tooth surfaces.

The Caenorhabditis elegans T-box factor MLS-1 requires Groucho co-repressor interaction for uterine muscle specification.

T-box proteins are conserved transcription factors that play crucial roles in development of all metazoans; and, in humans, mutations affecting T-box genes are associated with a variety of congenital diseases and cancers. Despite the importance of this transcription factor family, very little is known regarding how T-box factors regulate gene expression. The Caenorhabditis elegans genome contains 21 T-box genes, and their characterized functions include cell fate specification in a variety of tissues.