Born in the cold: contrasted thermal exchanges and maintenance costs in juvenile and adult snow buntings on their breeding and wintering grounds.

Several species of passerines leave their nest with unfinished feather growth, resulting in lower feather insulation and increased thermoregulatory demands compared to adults. However, feather insulation is essential for avian species breeding at northern latitudes, where cold conditions or even snowstorms can occur during the breeding season. In altricial arctic species, increased heat loss caused by poor feather insulation during growth could be counter-adaptative as it creates additional energy demands for thermoregulation.

A highly sensitive and selective LC-MS/MS method to quantify asunaprevir, an HCV NS3 protease inhibitor, in human plasma in support of pharmacokinetic studies.

Asunaprevir (BMS-650032) is a selective hepatitis C virus (HCV) NS3 protease inhibitor with potent activity against HCV genotypes 1, 4, 5 and 6. It has been developed in conjunction with direct-acting antiviral agents, in interferon- and ribavirin-free regimen, to improve existing therapies for HCV infection. To support the pharmacokinetic analyses in asunaprevir clinical studies, we have developed and validated a highly sensitive and robust LC-MS/MS method to quantify asunaprevir in human EDTA plasma with an LLOQ of 0.

Multiplexed LC-MS/MS method for the simultaneous quantitation of three novel hepatitis C antivirals, daclatasvir, asunaprevir, and beclabuvir in human plasma.

Dual or triple combination regimens of novel hepatitis C direct-acting antivirals (DAA, daclatasvir, asunaprevir, or beclabuvir) provide high sustained virological response rates and reduced frequency of resistance compared to clinical monotherapy. To support pharmacokinetic (PK) assessments in clinical studies, a multiplexed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitation of daclatasvir, asunaprevir, beclabuvir (BMS-791325) and its active metabolite (BMS-794712) in human plasma was developed and validated. Human plasma samples were extracted with methyl-t-butyl ether followed by an LC-MS/MS analysis, which was conducted in a multiple reaction monitoring (MRM) mode.

Sensitive and accurate liquid chromatography-tandem mass spectrometry methods for quantitative determination of a novel hepatitis C NS5B inhibitor BMS-791325 and its active metabolite in human plasma and urine.

BMS-791325 is a novel hepatitis C NS5B inhibitor which is currently in clinical development. To support pharmacokinetic (PK) assessments, sensitive, accurate, precise, and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed and validated for the quantitation of BMS-791325 and its active N-demethyl metabolite (BMS-794712) in human plasma and urine. Plasma and urine samples were extracted with methyl-t-butyl ether followed by an LC-MS/MS analysis which was conducted in a multiple reaction monitoring (MRM) mode for the simultaneous detection of the two analytes in human plasma (0.

Quantitative determination of free/bound atazanavir via high-throughput equilibrium dialysis and LC-MS/MS, and the application in ex vivo samples.

Aim: The determination of drug-protein binding is important in the pharmaceutical development process because of the impact of protein binding on both the pharmacokinetics and pharmacodynamics of drugs. Equilibrium dialysis is the preferred method to measure the free drug fraction because it is considered to be more accurate. The throughput of equilibrium dialysis has recently been improved by implementing a 96-well format plate.

Interactions and structural variability of β-carboxysomal shell protein CcmL.

CcmL is a small, pentameric protein that is argued to fill the vertices of β-carboxysomal shell. Here we report the structures of two CcmL orthologs, those from Nostoc sp. PCC 7120 and Thermosynechococcus elongatus BP-1.

Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study.

Context: Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment.

Subdomain location of mutations in cardiac actin correlate with type of functional change.

Determining the molecular mechanisms that lead to the development of heart failure will help us gain better insight into the most costly health problem in the Western world. To understand the roles that the actin protein plays in the development of heart failure, we have taken a systematic approach toward characterizing human cardiac actin mutants that have been associated with either hypertrophic or dilated cardiomyopathy. Seven known cardiac actin mutants were expressed in a baculovirus system, and their intrinsic properties were studied.

Liquid chromatography and tandem mass spectrometry method for the quantitative determination of saxagliptin and its major pharmacologically active 5-monohydroxy metabolite in human plasma: method validation and overcoming specific and non-specific binding at low concentrations.

A liquid chromatography and tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the concentrations of saxagliptin (Onglyza™, BMS-477118) and its major active metabolite, 5-hydroxy saxagliptin to support pharmacokinetic analyses in clinical studies. The dynamic range of the assay was 0.1-50 ng/mL for saxagliptin and 0.

Dalbavancin: Quantification in human plasma and urine by a new improved high performance liquid chromatography-tandem mass spectrometry method.

Dalbavancin is a novel second-generation lipoglycopeptide antibiotic with activity against broad range of Gram-positive pathogens. In order to determine the pharmacokinetics (PK) of dalbavancin in pediatric patients, a new High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) bioanalytical method has been developed for quantification of dalbavancin in plasma and in urine. The plasma method was validated for dalbavancin in the linear range from 0.

Primary care perspectives on prostate cancer survivorship: implications for improving quality of care.

Objectives: Primary care providers often care for men with prostate cancer due to its prolonged clinical course and an increasing number of survivors. However, their attitudes and care patterns are inadequately studied. In this context, we surveyed primary care providers regarding the scope of their prostate cancer survivorship care.

Primary care perspectives on prostate cancer screening.

Although the effectiveness of prostate cancer screening is controversial, screening rates have risen dramatically among primary care providers in the United States. The authors' findings suggest more collaboration among primary care and specialty organizations, especially with respect to decision aid endorsement, is needed to achieve more discriminatory and patient-centered prostate cancer screening.

Arginylation regulates intracellular actin polymer level by modulating actin properties and binding of capping and severing proteins.

Actin arginylation regulates lamella formation in motile fibroblasts, but the underlying molecular mechanisms are unknown. To understand how arginylation affects the actin cytoskeleton, we investigated the biochemical properties and the structural organization of actin filaments in wild-type and arginyltransferase (Ate1) knockout cells. We found that Ate1 knockout results in a dramatic reduction of the actin polymer levels in vivo accompanied by a corresponding increase in the monomer level.

Effect of socioeconomic factors on long-term mortality in men with clinically localized prostate cancer.

Objectives: To examine the effect of socioeconomic factors on survival in black and white patients with local or regional prostate cancer.

Methods: All cases (n = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at the Henry Ford Health System and the Henry Ford Medical Group, equal access health centers, were included. Data on the stage, grade, age at diagnosis, socioeconomic status, treatment given, comorbidities, and vital statistics were gathered from the Henry Ford Medical Group tumor registry and computerized databases, pathologic reports, patient charts, Surveillance, Epidemiology, and End Results database, and the national death registry.

Factors contributing to the racial differences in prostate cancer mortality.

Objective: To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African-Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups.

Patients And Methods: Clinical, pathological, and demographic data from 4279 men diagnosed with clinically localized prostate cancer between 1980 and 1997 were used. The variables assessed included age, disease stage, tumour grade, comorbidities, treatment method, and socio-economic status (SES).

Detection of trichothecene mycotoxins in sera from individuals exposed to Stachybotrys chartarum in indoor environments.

To date, no study has effectively demonstrated a direct human exposure to mycotoxins in mold-contaminated buildings. Therefore, the authors investigated the presence of trichothecene mycotoxins in sera from individuals exposed to indoor molds (specifically Stachybotrys chartarum). Sera from occupants of contaminated (test samples, n=44) and uncontaminated (control samples, n=26) buildings were analyzed using a competitive enzyme-linked immunosorbent assay (ELISA) highly specific for macrocyclic trichothecenes.

Sexually transmitted diseases and other urogenital conditions as risk factors for prostate cancer: a case--control study in Wayne County, Michigan.

Unlabelled: OBJECTIVE To investigate associations between prostate cancer and sexually transmitted diseases (STDs), prostatitis, benign prostatic hyperplasia (BPH), and vasectomy in a population-based case-control study in Wayne County, Michigan, among African American and white men aged 50--74 years.

Methods: Incident prostate cancer cases (n=700) from 1996--1998 were identified from the Metropolitan Detroit Cancer Surveillance System. Controls (n=604) were identified through random digit dialing and Medicare recipient lists, and frequency matched to cases on age and race.

Effects of false-positive prostate cancer screening results on subsequent prostate cancer screening behavior.

Objectives: Little is known about screening behavior following a false-positive prostate cancer screening result, which we have defined as a screening result with "abnormal/suspicious" labeling that did not result in a prostate cancer diagnosis within 14 months. The purpose of this analysis was to examine whether age, race, education, or previous false-positive prostate cancer screening results via prostate-specific antigen or digital rectal exam predict decision to obtain subsequent prostate cancer screening.

Methods: Data were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Determination of derivatized l-alanosine in plasma by liquid chromatography-tandem mass spectrometry.

A sensitive method was developed for quantitation of the cytotoxic antibiotic l-alanosine in human plasma. Alanosine was extracted from plasma by anion-exchange solid phase extraction, derivatized with dansyl chloride and analyzed by liquid chromatography-tandem mass spectrometry using atmospheric pressure chemical ionization in negative mode. Dansylation led to 50-fold improvement of method sensitivity over non-dansylated alanosine with a resulting 20 ng/ml limit of alanosine quantitation in plasma being achieved.

Long-term survival probability in men with clinically localized prostate cancer: a case-control, propensity modeling study stratified by race, age, treatment and comorbidities.

Purpose: We used a propensity risk scoring approach to model long-term survival for men with clinically localized prostate cancer. We developed comprehensive lookup tables for estimating survival probability stratified by patient age, race, readily available clinical variables, comorbidities and treatment type.

Materials And Methods: We retrospectively identified a cohort of 1611 men with clinically localized prostate cancer (patients) and 4538 age, race and comorbidity matched controls.

Recombinant human erythropoietin usage in a large academic medical center.

Objective: Recombinant human erythropoeitin (rhEPO) is a highly effective but expensive drug used for the treatment of certain anemias. We considered opportunities to curtail inpatient rhEPO utilization in light of therapeutic alternatives, the drug's delayed onset of action, and the available literature.

Study Design: A retrospective review of rhEPO administration in a large academic medical center between February and June 2000 was conducted by using administrative databases.

Relevant patient and tumor considerations for early prostate cancer treatment.

Prostate cancer remains the most commonly diagnosed noncutaneous malignancy in American men. Currently, there are 3 standard treatment options available to men with early prostate cancer: expectant management, radiation therapy, and radical prostatectomy. Although a number of studies have evaluated survival after treatment for early prostate cancer, the optimal choice of therapy for any given patient remains a difficult decision and requires the consideration of a variety of patient and tumor factors.

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

Background And Purpose: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence.