Identification of in vitro metabolites of indinavir by “intelligent automated LC-MS/MS” (INTAMS) utilizing triple quadrupole tandem mass spectrometry

AbstractIn an effort to improve the efficiency of the TSQ 7000 LC-MS/MS system for identification of drug metabolites in biological matrices in support of drug discovery programs, a combination of instrument control language procedures for the Finnigan MAT TSQ 7000 mass spectrometer, referred to as INTAMS, were composed. INTAMS was designed to conduct unattended, automatic liquid chromatography/mass spectrometry (LC-MS) and LC-MS/MS analyses of drugs and metabolites in commonly encountered in vitro biological matrices. A novel peak detection algorithm was developed to automatically detect and record the pseudomolecular ions and retention times of chromatographic components, even if not fully resolved. This algorithm was used in combination with an automated technique for predicting the molecular weights of metabolites based on incremental changes of the molecular weight of the parent drug resulting from well-known biotransformation processes. When applied to a sample of an incubation mixture of the HIV protease inhibitor Indinavir with a rat liver S9 preparation, the results obtained by the automatic metabolite detection procedures for LC-MS and LC-MS/MS analyses in real time were the same as those which were determined manually, by a knowledgeable operator

Ares I-X Flight Test--The Future Begins Here

In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission

Using optimal foraging theory to infer how groups make collective decisions

A growing body of evidence emerging from the analysis of advanced animal tracking data shows that moving groups make shared decisions about where to go, with each group member influencing the outcome. How groups coordinate departure decisions (when to go), however, remains poorly understood. Classic models from optimal foraging theory, specifically the marginal value theorem (MVT), are well-established tools that can generate quantitative predictions about when individuals should prefer to leave a food patch, given patch quality and the distribution of patches in the environment. Integrating optimal foraging theory into studies of animal collectives provides rich opportunities for gaining new insights from both empirical and theoretical studies. Specifically, the MVT can be used to make predictions about conflict of interests among group members, how consensus costs vary under different models of collective decision-making, and under what environmental conditions shared decision-making may be favored or disfavored

Novice Teachers Navigating Mentoring Relationships in the United States

Devido à escassez nacional de professores nos Estados Unidos, a manutenção desses profissionais no sistema é hoje mais crítica do que nunca. Nesta linha, este estudo visa compreender que experiências de tutoria e apoio à indução podem auxiliar neste objetivo. Enquadrada pela teoria do dialogismo de Bakhtin, a natureza longitudinal e qualitativa deste estudo explora as experiências de professores iniciantes (PI) em escolas dos primeiros anos de escolarização nos Estados Unidos, cujo desempenho profissional inicial ocorreu num cenário de pandemia global. Mais especificamente, concentramo-nos no apoio formal e informal que receberam nesses primeiros anos de exercício. A análise dos dados, que incluiu entrevistas aprofundadas com os PI, revelou dois temas principais: 1) despriorização da tutoria e 2) inconsistências na tutoria. As implicações deste estudo ampliam a literatura existente, oferecendo evidências baseadas em ações para melhorar a orientação e a indução. O foco na manutenção de PI no sistema através de suporte e orientação beneficia está área no presente e no futuro.Amid the national teaching shortage in the United States, it is now more critical than ever to sustain teachers. Consequently, the purpose of this study is to understand which mentoring experiences and induction support can aid in this objective.  Framed by Bakhtin’s theory of dialogism, this study's longitudinal, qualitative nature explores the experiences of novice teachers (NTs) in elementary schools in the United States whose critical first years occurred amid a global pandemic.  More specifically, we focus on the formal and informal support they experienced while becoming a teacher.  Analysis of the data, which included in-depth interviews with the NTs revealed two key themes: 1) deprioritizing mentoring, and 2) inconsistencies in mentoring.  The implications of this study aim to extend the existing literature, offering action-based evidence to improve mentoring and induction.  Focusing on the retention of NTs via support and mentoring benefits the field now and into the future

Integrated Vehicle Ground Vibration Testing in Support of Launch Vehicle Loads and Controls Analysis

All structural systems possess a basic set of physical characteristics unique to that system. These unique physical characteristics include items such as mass distribution and damping. When specified, they allow engineers to understand and predict how a structural system behaves under given loading conditions and different methods of control. These physical properties of launch vehicles may be predicted by analysis or measured by certain types of tests. Generally, these properties are predicted by analysis during the design phase of a launch vehicle and then verified by testing before the vehicle becomes operational. A ground vibration test (GVT) is intended to measure by test the fundamental dynamic characteristics of launch vehicles during various phases of flight. During the series of tests, properties such as natural frequencies, mode shapes, and transfer functions are measured directly. These data will then be used to calibrate loads and control systems analysis models for verifying analyses of the launch vehicle. NASA manned launch vehicles have undergone ground vibration testing leading to the development of successful launch vehicles. A GVT was not performed on the inaugural launch of the unmanned Delta III which was lost during launch. Subsequent analyses indicated had a GVT been performed, it would have identified instability issues avoiding loss of the vehicle. This discussion will address GVT planning, set-up, execution and analyses, for the Saturn and Shuttle programs, and will also focus on the current and on-going planning for the Ares I and V Integrated Vehicle Ground Vibration Test (IVGVT)

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Preliminary Analysis of in Utero Low-Level Arsenic Exposure and Fetal Growth Using Biometric Measurements Extracted from Fetal Ultrasound Reports

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. Results: In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value \u3c 0.05). Although, associations were attenuated in adjusted analyses — among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: −0.151, 0.007) decrease in biparietal head diameter Z-score. Conclusions: Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation

Characterizing Short-Wave Infrared Fluorescence of Conventional Near-Infrared Fluorophores

The observed behavior of short-wave infrared (SWIR) light in tissue, characterized by relatively low scatter and subdiffuse photon transport, has generated considerable interest for the potential of SWIR imaging to produce high-resolution, subsurface images of fluorescence activity in vivo. These properties have important implications for fluorescence-guided surgery and preclinical biomedical research. Until recently, translational efforts have been impeded by the conventional understanding that fluorescence molecular imaging in the SWIR regime requires custom molecular probes that do not yet have proven safety profiles in humans. However, recent studies have shown that two readily available near-infrared (NIR-I) fluorophores produce measurable SWIR fluorescence, implying that other conventional fluorophores produce detectable fluorescence in the SWIR window. Using SWIR spectroscopy and wide-field SWIR imaging with tissue-simulating phantoms, we characterize and compare the SWIR emission properties of eight commercially available red/NIR-I fluorophores commonly used in preclinical and clinical research, in addition to a SWIR-specific fluorophore. All fluorophores produce measurable fluorescence emission in the SWIR, including shorter wavelength dyes such as Alexa Fluor 633 and methylene blue. This study is the first to report SWIR fluorescence from six of the eight conventional fluorophores and establishes an important comparative reference for developing and evaluating SWIR imaging strategies for biomedical applications

NASA Crew Launch Vehicle Flight Test Options

Options for development flight testing (DFT) of the Ares I Crew Launch Vehicle (CLV) are discussed. The Ares-I Crew Launch Vehicle (CLV) is being developed by the U.S. National Aeronautics and Space Administration (NASA) to launch the Crew Exploration Vehicle (CEV) into low Earth Orbit (LEO). The Ares-I implements one of the components of the Vision for Space Exploration (VSE), providing crew and cargo access to the International Space Station (ISS) after retirement of the Space Shuttle and, eventually, forming part of the launch capability needed for lunar exploration. The role of development flight testing is to demonstrate key sub-systems, address key technical risks, and provide flight data to validate engineering models in representative flight environments. This is distinguished from certification flight testing, which is designed to formally validate system functionality and achieve flight readiness. Lessons learned from Saturn V, Space Shuttle, and other flight programs are examined along with key Ares-I technical risks in order to provide insight into possible development flight test strategies. A strategy for the first test flight of the Ares I, known as Ares I-1, is presented