Is it the method or the process-separating the causes of low recovery

During the development of a tablet formulation, a solvent capable of extracting 100% of the drug from the tablet excipients must be identified as part of the analytical assay method. When a low drug recovery from a tablet is observed with the assay method, it must be determined whether a problem with the manufacturing process exists, or if the extraction of the drug was incomplete. A solvent screen study was conducted with CP-122,721 prototype formulations to select a robust solvent for the assay method. However, low tablet assay values (ca. 95%) were routinely observed during tablet formulation development and process scale up. Drug-excipient interactions in a variety of solvents were subsequently evaluated to confirm the selection of the extraction solvent as capable of 100% extraction. At this point the focus of the investigation was placed on process-related sources of low recovery, such as loss of drug to manufacturing equipment and/or segregation during the tableting process. The results suggest that the low drug recovery observed for the CP-122,721 tablets was due to segregation during the manufacture, while the selected extraction solvent was able to eliminate any interactions between CP-122,721 and the tablet excipients.     

The Effect of Different Sterilization Methods on the Mechanical Strength of Magnesium Based Implant Materials

The research on the development and characterization of potential magnesium biomaterials is a steadily expanding. Commonly, implants present a high risk of infection for their recipients. For this reason, a pre‐operative sterilizing process is required. Due to the temperatures and media which are used while sterilizing, effects may occur which cause a change in the mechanical strength of certain magnesium alloys. Four commonly used sterilization methods (autoclave sterilization, dry heat sterilization, gamma sterilization and ethylene oxide sterilization) were investigated to gain information about their influences on the quasi‐static mechanical behavior of LAE442 (Mg 90 m.%, Li 4 m.%, Al 4 m.%, RE 2 m.%), MgCa0.8 (Mg 99.2 m.%, Ca 0.8 m.%) magnesium alloys as well as pure magnesium. The mechanical properties exhibited by the sterilized and non‐sterilized alloys refer to susceptibilities of the mechanical strengths to the investigated sterilization methods. Such susceptibilities appear to be dependent on the combination of alloy and method of sterilization. However, the maximum changes in mechanical strength appear in the range of ±10%. Within this study, ETO sterilization caused the least changes in the mechanical strength of the alloys and appears to be the best performer.     

Finding a minimally informative Dirichlet prior distribution using least squares

In a Bayesian framework, the Dirichlet distribution is the conjugate distribution to the multinomial likelihood function, and so the analyst is required to develop a Dirichlet prior that incorporates available information. However, as it is a multiparameter distribution, choosing the Dirichlet parameters is less straightforward than choosing a prior distribution for a single parameter, such as p in the binomial distribution. In particular, one may wish to incorporate limited information into the prior, resulting in a minimally informative prior distribution that is responsive to updates with sparse data. In the case of binomial p or Poisson λ, the principle of maximum entropy can be employed to obtain a so-called constrained noninformative prior. However, even in the case of p, such a distribution cannot be written down in the form of a standard distribution (e.g., beta, gamma), and so a beta distribution is used as an approximation in the case of p. In the case of the multinomial model with parametric constraints, the approach of maximum entropy does not appear tractable. This paper presents an alternative approach, based on constrained minimization of a least-squares objective function, which leads to a minimally informative Dirichlet prior distribution. The alpha-factor model for common-cause failure, which is widely used in the United States, is the motivation for this approach, and is used to illustrate the method. In this approach to modeling common-cause failure, the alpha-factors, which are the parameters in the underlying multinomial model for common-cause failure, must be estimated from data that are often quite sparse, because common-cause failures tend to be rare, especially failures of more than two or three components, and so a prior distribution that is responsive to updates with sparse data is needed.     

Spin-on spintronics: ultrafast electron spin dynamics in ZnO and Zn₁-xCoxO sol-gel films

We use time-resolved Faraday rotation spectroscopy to probe the electron spin dynamics in ZnO and magnetically doped Zn(1-x)Co(x)O sol-gel thin films. In undoped ZnO, we observe an anomalous temperature dependence of the ensemble spin dephasing time T(2), i.e., longer coherence times at higher temperatures, reaching T(2) ～ 1.2 ns at room temperature. Time-resolved transmission measurements suggest that this effect arises from hole trapping at grain surfaces. Deliberate addition of Co(2+) to ZnO increases the effective electron Lande? g factor, providing the first direct determination of the mean-field electron-Co(2+) exchange energy in Zn(1-x)Co(x)O (N(0)α = +0.25 ± 0.02 eV). In Zn(1-x)Co(x)O, T(2) also increases with increasing temperature, allowing spin precession to be observed even at room temperature.     

Liposome and lipid bilayer arrays towards biosensing applications

Sensitive and selective biosensors for high-throughput screening are having an increasing impact in modern medical care. The establishment of robust protein biosensing platforms however remains challenging, especially when membrane proteins are involved. Although this type of proteins is of enormous relevance since they are considered in >60% of the pharmaceutical drug targets, their fragile nature (i.e., the requirement to preserve their natural lipid environment to avoid denaturation and loss of function) puts strong additional prerequisites onto a successful biochip. In this review, the leading approaches to create lipid membrane-based arrays towards the creation of membrane protein biosensing platforms are described. Liposomes assembled in micro- and nanoarrays and the successful set-ups containing functional membrane proteins, as well as the use of liposomes in networks, are discussed in the first part. Then, the complementary approaches to create cell-mimicking supported membrane patches on a substrate in an array format will be addressed. Finally, the progress in assembling free-standing (functional) lipid bilayers over nanopore arrays for ion channel sensing will be reported. This review illustrates the rapid pace by which advances are being made towards the creation of a heterogeneous biochip for the high-throughput screening of membrane proteins for diagnostics, drug screening, or drug discovery purposes.     

Optimisation of fibre steering in composite laminates using a genetic algorithm

An optimization procedure using a genetic algorithm has been applied to define the optimum orientation of fibres in a uni-directional laminate in which the fibres were allowed to vary continuously across the domain. The domain was divided into two-dimensional finite elements and anisotropic properties corresponding to a carbon fibre laminate with all layers aligned in the zero element axis direction were applied to the laminate. The orientation of the material axis on each element was then prescribed as an independent variable for the genetic algorithm.     

Low birth weight and cognitive outcomes: Evidence for a gradient relationship in an urban, poor, African American birth cohort.

This study is one of the first to investigate the relationship between low birth weight and cognitive outcomes in an urban, poor, prospectively designed African-American birth cohort. Multivariate analyses of the Pathways to Adulthood study, a subset of the Johns Hopkins Collaborative Perinatal study, compared low birth weight African-American children with normal birth weight African-American children on the Wechsler Intelligence Scale for Children (WISC) at seven years of age. When controlling for various sociodemographic factors, associations were obtained for the very low birth weight group (less than 2000 g) indicating an overall 7 point IQ difference. Milder associations were reported in the moderately low birth weight (MLBW) group (2000 to 2500 g) resulting in a 3 IQ point decrement compared to a normal birth weight reference group. There were no differential effects for gender. Our study revealed a gradient relationship between low birth weight/preterm birth and cognitive ability. Implications for school psychology prevention, assessment, and intervention are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Language exclusion and the consequences of perceived ostracism in the workplace.

The current research examined the impact of workplace ostracism on work-related attitudes and behaviors. Participants read a vignette describing a series of workplace interactions between the participant and two coworkers. During the interactions, participants were included in a group discussion, ostracized by coworkers in English or ostracized in Spanish. Consistent with predictions, ostracized participants reported lower levels of organizational commitment and organizational citizenship behaviors than included participants. Ostracism by language resulted in lower work group commitment and higher levels of symbolic threat compared with included participants and those ostracized in English. Increased prejudice was also reported by participants exposed to language ostracism. Results are discussed in terms of their implications for general attitudinal processes and employee-related work attitudes and behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Worst Practices for Domain-Specific Modeling

Interest in creating domain-specific modeling (DSM) languages is surging, but little guidance is available on how to do it right. Along with heeding best practices, learning what not to do—including how to handle common pitfalls and recognize troublesome areas—can help first-time developers. The authors have identified several worst practices based on an analysis of 76 DSM cases spanning 15 years, four continents, several tools, around 100 language creators, and projects with from three to more than 300 modelers. They present these worst practices in the order that language developers would encounter them over the life of a project.