MALDI-TOF MS: an upcoming tool for rapid detection of antibiotic resistance in microorganisms

MALDI-TOF MS profiling for microorganism detection has already been demonstrated in the 1990s, but has evolved to the first-line identification method in many laboratories just during the past five years. While this application of MALDI-TOF MS has proven its broad applicability, accuracy, robustness, and cost-effectiveness it is of particular interest to expand the capabilities of the mass spectrometric platform. Resistance detection is the most desirable further application of MALDI-TOF MS in microbiology, but maybe also the most challenging. Different approaches have been published regarding diverse antibiotic drugs and distinct microorganism classes. The current review shall give an overview about the developments of the recent years and their potential to get transformed in clinical useful assays in the future.     

Enhancement of Upconverted Fluorescence by Interference Layers

Upconverting nanoparticles show potential applications in the field of photovoltaics and array‐based detection devices. While fluorescence enhancement using interference of incident radiation is well known in Stokes‐shift type systems such as fluorescent dyes; the effect of such interference geometry in nonlinear Anti‐Stokes type emission, such as in upconversion rare earth photophysics is demonstrated for the first time. This work describes in detail the influence of the interference modulation on both the excitation (interion energy transfer) and radiative decay with nonradiative decay processes active between emissive levels. These effects are illustrated in the thickness dependence of the decay rate and rise time. Single particle upconverted spectra and time‐resolved measurements show concurrent optimization of the infrared absorption and emission at 540 and 650 nm, with an average enhanced emission of 20 times at λ = 540 and 45 times at λ = 650 nm, dependent on the interference layer thickness and on the excitation intensity. The experimental results are correlated with finite element modeling. Both experiments and calculations show emission enhancement at an interference layer thickness of about 740 ± 20 nm, where such tolerance and the planar design, leads to ease in implementation in applications.     

Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review

Context: Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model.

Objective: The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms.

Methods: Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described.

Results: There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of “from powder to tablet” is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible.

Conclusion: A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.     

Locating computer clubs in multicultural neighborhoods: How collaborative project work fosters integration processes

Located in socially and culturally diverse neighborhoods, we have built a network of intercultural computer clubs, called come_IN. These clubs offer a place to share practices among children and adults of diverse ethnical backgrounds. We show how this initiative ties into the striving for the integration of migrant communities and host society in Germany. In this paper, we analyze how collaborative project work and the use of mobile media and technologies contribute to integration processes in multicultural neighborhoods. Qualitative data gathered from interviews with club participants, participative observation in the computer clubs, as well as the analysis of artifacts created during project work provides the background needed to match local needs and peculiarities with (mobile) technologies. Based on these findings we present two approaches to add to the technological infrastructure: (1) a mesh-network extending the clubs into the neighborhood and (2) a project management tool, which supports projects and stimulates the sharing of ideas among projects.     

Using a flatbed scanner as a stereoscopic near-field camera

It is shown that flatbed scanners are inherently high quality 3D scanners. Currently developed first prototypes have many applications in industry and multimedia. Because of their big depth of focus, they can be used not only for scanning printed paper, but also for scanning small objects. The nonparallel optics also make it possible to create stereoscopic images of small objects with flatbed scanners, as first described elsewhere (R. Schubert, 1998). The author describes the method for doing this. He also shows examples of stereoscopic images made in this way so that you can judge for yourself their quality and particular properties. Finally, he describes possible accessories that will let you use flatbed scanners routinely in a lot of areas, including hobbies and professional applications. Combining dedicated 3D imaging and evaluation software as well as 3D output devices results in a high quality, low cost 3D scanner. Currently work is under way to specify, design, and build the first prototypes     

Bridging the Gap between Legal and Technical Contracts

Two or more parties typically establish a business relationship using a contract, but a large gap still exists between the provisions of contracts produced by lawyers and the details of computer security and performance addressed by technologists. Some contractual clauses address legal issues that technology can manage as well - the TrustCoM framework offers a paradigm for automating these clauses as technical operations. If a business relationship forms across a service-oriented architecture, the parties involved often manage their collaboration as a virtual organization (VO). In TrustCoM, agreements are the key means of steering VO collaborations and mitigating the risks inherent in integrating processes and resources across organizational boundaries.     

Measurements of superfluid densities and critical superfluid mass currents of pure 4He and 3He/4He mixtures in nuclepore near the lambda transition

Measurements have been made of the relative superfluid density _sp/ and the critical mass current I _sc for the onset of dissipation in the superfluid flow of pure ⁴He and ³He/⁴He mixtures in the circular cylindrical pores of Nuclepore near the transition, using a double-ended Helmholtz resonator. Pore diameters of 0.03, 0.1, and 0.4 m were studied using ³He mole fractions of 0.0,0.2, and 0.4. For each pore diameter d _p and mole fraction x our results for _sp / were fitted relatively well by the form C(t – t ₀₁)^0.675 and those for I _sc by the form I _sc0(t–t _0c ) ^g , where t [T –T]/T . For each combination of d _p and x the reduced onset temperatures t ₀₁ and t _0c are in rough agreement with each other but somewhat larger than values found by others for Nuclepore. For the smaller two pore diameters, these onset temperatures are consistent with the universality hypothesis that near T, ² _sb /m ₄ ² k _B T should be a constant independent of T and x. Here is the reduced Planck constant, _sb is the bulk superfluid density, is the coherence length, m ₄ is the ⁴He atom mass, k _B is Boltzmann's constant, and T is the absolute temperature. At each value of x the amplitudes C agree well with the corresponding amplitude for _sb /, and g equals 1.17 ± 0.04 for all cases. Measurements of the velocity of second sound at x = 0.000, 0.190, 0.401, and 0.450 are also reported.Work supported by U.S. Department of Energy contract EY-76-S-02-1569.     

Efficient data management in a large-scale epidemiology research project

This article describes the concept of a "Central Data Management" (CDM) and its implementation within the large-scale population-based medical research project "Personalized Medicine". The CDM can be summarized as a conjunction of data capturing, data integration, data storage, data refinement, and data transfer. A wide spectrum of reliable "Extract Transform Load" (ETL) software for automatic integration of data as well as "electronic Case Report Forms" (eCRFs) was developed, in order to integrate decentralized and heterogeneously captured data. Due to the high sensitivity of the captured data, high system resource availability, data privacy, data security and quality assurance are of utmost importance. A complex data model was developed and implemented using an Oracle database in high availability cluster mode in order to integrate different types of participant-related data. Intelligent data capturing and storage mechanisms are improving the quality of data. Data privacy is ensured by a multi-layered role/right system for access control and de-identification of identifying data. A well defined backup process prevents data loss. Over the period of one and a half year, the CDM has captured a wide variety of data in the magnitude of approximately 5terabytes without experiencing any critical incidents of system breakdown or loss of data. The aim of this article is to demonstrate one possible way of establishing a Central Data Management in large-scale medical and epidemiological studies.