Using Structural Equation Modeling (SEM) for the Study of Impurity Profiles of Drug Substances

The impurity profile is one of the most important quality characteristics of a drug substance. Although it is always desirable to determine the chemical structure of all impurities forming the impurity profile, unfortunately this is not always economically and technically feasible because of the extremely low concentrations at which some impurities may be found in the drug substance. Therefore, alternative approaches to the chemical analysis are needed for trying to determine the origin of the unidentified impurities.

In a previous study conducted by our group, based on exploratory (principal component and hierarchical cluster) analysis, we were able to suggest a hypothesis for explaining the origin of the unidentified impurities of a drug substance. However, there was still a concern that alternative hypotheses might explain the same phenomenon equally well. This article explores the application of recent developments in structural equation modeling for the systematic generation and selection of hypotheses (models) worthy of being confirmed by chemical research.     

Detection and Discrimination of Conspecific Scents by the Anguid Slow-Worm Anguis fragilis

We tested the ability of male slow-worms, Anguis fragilis, a limbless anguid lizard with secretive, semifossorial habits, to detect chemical associated with conspecifics by using a T-maze in the laboratory. Male slow-worms discriminated conspecific male and female scent deposits. Males selected the arm with female scent, suggesting that scent deposits may be used to locate potential mates. Also, male slow-worms did not avoid the chemicals of other males, suggesting that they are not territorial. However, males discriminated their own scent from those of other males, and spent more time exploring the arm with other male scent, which suggests that scent marks may bear information that could be used in future intrasexual social contexts. We conclude that discrimination of conspecifics based on scents may be more widespread than previously expected among lizards inhabiting visually restricted environments.     

Dual holographic interferometry for measuring the three velocity components in a fluid plane

A technique that allows one to measure simultaneously the three velocity components in a fluid plane is presented. One obtains the quantitative information from only one holographic recording by combining two different reconstruction processes. As both processes use an interferometric comparison of two waves, we refer to this technique as dual holographic interferometry. The far-field fringe pattern that is obtained when reconstruction is made with an expanded laser beam allows one to determine the in-plane velocity components. The image-field fringe pattern that is obtained when a pointwise laser beam is used for reconstruction contains information about an out-of-plane velocity component. As the two reconstruction processes have different sensitivities, two different ways to combine them are proposed. The system has been demonstrated in a fluidlike solid object and in a convective flow.     

Accuracy of BRT and Delvotest microbial inhibition tests as affected by composition of ewe's milk

The presence of drug residues in ewe's milk samples can be determined by microbial assays. The main limitation of these tests is the large number of false-positive results associated with them. False-positive results can be explained by the interaction of certain substances naturally existing in ewe's milk with the growth of the microorganism used in the test. In this study, milk chemical composition (fat, protein, lactose, total solids), somatic cell counts (SCCs), free fatty acid concentrations, and lactoperoxidase system components were determined in order to investigate their influence on the rate of false-positive results for the BRT and Delvotest microbiological inhibitor tests. Milk samples were obtained after morning milking of Manchega ewes at 15, 30, 45, 60, 75, 90, 105, 120, and 135 days after parturition. The animals did not receive any kind of treatment or medicated feed throughout the experiment. The false-positive rates for BRT and Delvotest were 3.75 and 2.4%, respectively. When the logistic regression model was applied, the percentages of total solids for positive samples were significantly different from those for negative samples (16.90 versus 18.42% for BRT, 16.05 versus 18.45% for Delvotest), while the SCC logarithmic transformation was significantly higher for the positive samples than for the negative samples (5.38 versus 5.11 log units for BRT, 5.32 versus 5.11 log units for Delvotest). Moreover, Delvotest-positive samples exhibited thiocyanate concentrations higher than those of Delvotest-negative samples (8.18 mg/liter versus 6.85 mg/liter). Further analyses are needed to confirm the possible presence of antimicrobial residues in this particular type of milk sample.     

MR imaging of baker cysts—prevalence and relation to internal derangements of the knee

Rationale and objectives: To evaluate the prevalence of popliteal cysts in patients studied with magnetic resonance (MR) imaging. Cyst presence and volume will be related to other internal derangement of the knee.Materials and methods: Three hundred and eighty-two consecutive patients with a MR study of the knee were included. Images were obtained in the three spatial orthogonal planes and evaluated through consensus. Four categories were established for the Baker cyst and synovial fluid (absence, minimum, moderate and massive), and the presence of meniscal, cruciate ligaments and cartilage lesions were recorded. Statistical analysis was carried out with bivariate analysis (χ² of Pearson and Gamma tests).Results: From the 382 patients, 145 had Baker cysts (38.0%). Cyst content was minimum in 99, moderate in 34 and massive in 12. Joint effusion was observed in 269 patients (70.4%), being minimal in 140 patients, moderate in 119 and massive in ten. Meniscal lesions were observed in 195 patients (51%), while 58 patients (15%) had a cruciate ligament lesion. Baker cyst has a statistically significant direct relationship with the presence and quantity of synovial fluid (P=0.002) and with the presence and type of meniscal lesion (P=0.01) but not with cruciate ligaments or cartilage lesions.Conclusions: The prevalence of Baker cysts in MR studies of the knee is high. Its presence and volume are related to the quantity of synovial fluid, and to the presence and severity of meniscal lesions.     

An approach for automatic generation of adaptive hypermedia in education with multilingual knowledge discovery techniques

This work describes a framework that combines techniques from Adaptive Hypermedia and Natural Language processing in order to create, in a fully automated way, on-line information systems from linear texts in electronic format, such as textbooks. The process is divided into two steps: an off-line processing step, which analyses the source text, and an on-line step, which executes when a user connects to the system with a web browser, moment at which the contents and hyperlinks are generated. The framework has been implemented as the Welkin system, which has been used to build three adaptive on-line information sites in a quick and easy way. Some controlled experiments have been performed with real users aimed to provide positive feedback on the implementation of the system.     

Asymptotic normality of the Nadaraya–Watson semivariogram estimators

In this work, the Nadaraya–Watson semivariogram estimation is considered for both the isotropic and the anisotropic settings. Several properties of these estimators are analyzed and, particularly, their asymptotic normality is established in terms of unknown characteristics of the random process. The latter provides a theoretical procedure for construction of confidence intervals for the semivariogram via the normal quantiles, which in practice must be appropriately estimated. A numerical study is included to illustrate the performance of the Nadaraya–Watson estimation when used to obtain confidence intervals.      

Toward the DSM-V: The Withdrawal-Gate Model versus the DSM-IV in the diagnosis of alcohol abuse and dependence.

The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) classifies as dependent many cases of mild alcohol problems. DSM-IV diagnoses have modest relationships with predictive and some concurrent validators and often improperly sequence the onset of abuse vs dependence, perhaps due to insufficient emphasis on physiological features. Testing reliability, syndrome prevalence, syndrome sequencing, and concurrent and predictive validity, this study contrasted the DSM-IV with the Withdrawal-Gate Model (WGM), in which alcohol withdrawal is necessary and sufficient for the dependence diagnosis. Clinical samples of adults (baseline n?=?318) and adolescents (baselinen?=?214) meeting abuse or dependence were assessed for DSM-IV alcohol symptoms and external measures of problem severity and reinterviewed at 6 (adults) and 12 mo (adults and adolescents). Among DSM-IV dependent cases, the WGM shifted 32% of adults and 80% of adolescents to the abuse category, making both categories more symptomatically severe, but had a negligible effect on prevalence of total alcohol diagnoses. The WGM was more reliable than the DSM-IV and temporally sequenced abuse before dependence in a greater number of cases. The WGM was superior to the DSM-IV in concurrent and predictive validity on most measures. Future diagnostic systems may be more reliable and valid if they require evidence of withdrawal for substance dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mental health professionals' adaptive responses to racial microaggressions: An exploratory study.

This study examines adaptive responses that mental health professionals of color use to cope with racial microaggressions in their professional lives. Twenty-four mental health professionals from diverse ethnic backgrounds in the United States and Canada participated in focus groups discussing their experiences with racial microagressions and how they cope with them. Results of the analysis indicated that 8 primary coping themes illustrated strategies used by the participants. These include: identifying key issues in responding to racial microaggressions, self-care, spirituality, confrontation, support, documentation, mentoring, and collective organizing. Suggestions for mentoring professionals of color are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of phenoloxidase activity of carapace and viscera from cephalothorax of Norway lobster (Nephrops norvegicus)

The characterization of phenoloxidase activity was performed in both carapace and viscera extracts of Norway lobster. Phenoloxidase activity rose with increasing temperature up to 60 °C. The carapace enzymatic extract showed the highest themostability, retaining about 80% of maximum activity at 45 °C and 40% at 65 °C. On the other hand, both enzymatic extracts showed a single peak activity at neutral-slightly alkaline pH and were quite resistant to inactivation at alkaline pH (pH > 8), but phenoloxidase activity became unstable at pH lower than 5.5. The enzymatic extract obtained from viscera showed a higher affinity for catechol (K_M 5.97 mM) than carapace extract (K_M 19.40 mM). Both mono- and diphenoloxidase activities were found in carapace and viscera. Polyphenoloxidase and converted-hemocyanin into PPO-like enzyme could be the main responsible for these activities.