Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis

The objective of this study was to investigate the interaction between levels of BAFF (B-cell activation factor of the tumour necrosis factor [TNF] family) and APRIL (a proliferation-inducing ligand) and B-cell frequencies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) treated with the B-cell-depleting agent rituximab. Ten patients with SLE were treated with rituximab in combination with cyclophosphamide and corticosteroids. They were followed longitudinally up to 6 months after B-cell repopulation. Nine patients with RA, resistant or intolerant to anti-TNF therapy, treated with rituximab plus methotrexate were investigated up to 6 months after treatment. The B-cell frequency was determined by flow cytometry, and serum levels of BAFF and APRIL were measured by enzyme-linked immunosorbent assays. BAFF levels rose significantly during B-cell depletion in both patient groups, and in patients with SLE the BAFF levels declined close to pre-treatment levels upon B-cell repopulation. Patients with SLE had normal levels of APRIL at baseline, and during depletion there was a significant decrease. In contrast, patients with RA had APRIL levels 10-fold higher than normal, which did not change during depletion. At baseline, correlations between levels of B cells and APRIL, and DAS28 (disease activity score using 28 joint counts) and BAFF were observed in patients with RA. In summary, increased BAFF levels were observed during absence of circulating B cells in our SLE and RA patient cohorts. In spite of the limited number of patients, our data suggest that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by rituximab treatment

Generic pregabalin : current situation and implications for health authorities, generics and biosimilars manufacturers in the future

The manufacturer of pregabalin has a second use patent covering prescribing for neuropathic pain: its principal indication. The manufacturer has threatened legal action in the UK if generic pregabalin rather than Lyrica is prescribed for this indication. No problems exist for practitioners who prescribe pregabalin for epilepsy or generalized anxiety disorder. This has serious implications for health authorities. In Germany, however, generics could be legally prescribed for any approved indication once one indication loses its patent. We aim to establish the current situation with pregabalin among principally European countries. Personnel from 33 regional and national health authorities mainly from Europe, and nine from universities across Europe working as advisers to health authorities or with insight into their activities, were surveyed regarding four specific questions via email to shed light on the current situation with Lyrica and pregabalin in their country. The information collated from each country was subsequently checked for accuracy with each co-author by email and face-to-face contact and collated into five tables. The scenarios ranged from extending the patent life of Lyrica (e.g. France), endorsing the prescribing of Lyrica for neuropathic pain (e.g. Catalonia and South Korea), and current prescribing of pregabablin for all indications (e.g. Serbia and Germany). Little activity has taken place in European countries in which generic pregabalin is not yet reimbursed. The availability of generic pregabalin has prompted a number of different activities to be undertaken among the 33 countries and regions surveyed. The situation in Serbia and the historic situation in Germany provide examples of ways to maximize savings once a product loses its patent for at least one indication

The Expression of VEGF-A Is Down Regulated in Peripheral Blood Mononuclear Cells of Patients with Secondary Progressive Multiple Sclerosis

BACKGROUND: Most patients with relapsing-remitting multiple sclerosis (RRMS) eventually enter a secondary progressive (SPMS) phase, characterized by increasing neurological disability. The mechanisms underlying transition to SPMS are unknown and effective treatments and biomarkers are lacking. Vascular endothelial growth factor-A (VEGF-A) is an angiogenic factor with neuroprotective effects that has been associated with neurodegenerative diseases. SPMS has a prominent neurodegenerative facet and we investigated a possible role for VEGF-A during transition from RRMS to SPMS. METHODOLOGY/PRINCIPAL FINDINGS: VEGF-A mRNA expression in peripheral blood mononuclear (PBMC) and cerebrospinal fluid (CSF) cells from RRMS (n = 128), SPMS (n = 55) and controls (n = 116) were analyzed using real time PCR. We demonstrate reduced expression of VEGF-A mRNA in MS CSF cells compared to controls (p<0.001) irrespective of disease course and expression levels are restored by natalizumab treatment(p<0.001). VEGF-A was primarily expressed in monocytes and our CSF findings in part may be explained by effects on relative monocyte proportions. However, VEGF-A mRNA expression was also down regulated in the peripheral compartment of SPMS (p<0.001), despite unchanged monocyte counts, demonstrating a particular phenotype differentiating SPMS from RRMS and controls. A possible association of allelic variability in the VEGF-A gene to risk of MS was also studied by genotyping for six single nucleotide polymorphisms (SNPs) in MS (n = 1114) and controls (n = 1234), which, however, did not demonstrate any significant association between VEGF-A alleles and risk of MS. CONCLUSIONS/SIGNIFICANCE: Expression of VEGF-A in CSF cells is reduced in MS patients compared to controls irrespective of disease course. In addition, SPMS patients display reduced VEGF-A mRNA expression in PBMC, which distinguish them from RRMS and controls. This indicates a possible role for VEGF-A in the mechanisms regulating transition to SPMS. Decreased levels of PBMC VEGF-A mRNA expression should be further evaluated as a biomarker for SPMS

Design and Implementation of NFC-based gym mobile app

This report investigates the technical and economic viability of introducing a Near Field Communication (NFC) client system in a gym environment. The system aims to aid the customers with logging their workout, retrieving information regarding exercises as well as enhancing the attendance control for both staff and customers. To identify what information to be presented, the most important quality factors and what functionalities are most desired, an exploratory case study was conducted. The study showed that there is a discrepancy between the desire to log ones workout and actually doing it. Most people want to keep track of how they workout, but despite the wide variety of workout applications on the market, they choose not to use them. The main concern expressed was that the logging needs to be fast and easy, indicating that the existing apps do not fulfill the ease of use desired. The system presented in this report is coupled to the gym where NFC tags pair an exercise to its corresponding logger and information in the application. The ability for the gym to track its customers’ workout habits is a rare feature that provides several economic benefits such as targeted advertisement, better maintenance control and new customer services analyzing their workout. For the system to be effective the customers need to use the system and log their workout, therefore it needs to be supported by the major mobile platforms. To accommodate this a hybrid platform approach using PhoneGap was used. This approach allows for development in one language that translates into native embedded web applications. At the time of writing Apple’s latest models do include the hardware for NFC communication. However, it is not possible to develop a custom NFC application for iPhone yet. By adopting the hybrid approach there is no need to create a whole new app when they do release the rights to do so. In conclusion, the technical viability of the NFC based system comes with the tradeoffs of dealing with the lack of standards of a new technology and being early on the market with a new feature. This calls for some custom solutions, since each platform adopts their own way of NFC implementation, but is manageable. The economic aspects are tied to the use of the system where the ease of use is the key factor for the customers. The end user tests indicate that NFC provides that small advantage over traditional workout applications needed to make logging attractive

All-fiber modulators for laser applications

The objective of this thesis was to explore the usefulness of all-fiber modulators for laser applications. The modulators were all based on refractive index change achieved in the core of the studied fiber- components, exploiting either the elasto-optic effect or the electro-optic effect. This was realized with the aid of electrodes inside the fiber cladding close to the core that provided either thermal stress in the core, or an electric field across the core. The electrodes consisted of low melting-point alloys, such as BiSn and AuSn, which were pushed into the hole-fiber, in the liquid state, which then solidified to form solid electrodes filling the entire hole. Together with an analyzer such as a polarizer or an interferometer the achieved refractive index modulation in the core could then be translated into an amplitude modulation of the guided light, which was subsequently utilized for switching fiber-lasers to generate cavity dumped, Q-switched, or mode-locked pulses. The fast rise/fall-time of a few nanoseconds for the elasto-optic devices was due to the fast thermal expansion of the electrodes. The maximum repetition rate, however, was limited to a few tens of kHz, due to the slow thermal processes for dissipation of the applied energy. The electro-optic fiber components, which displayed similar rise/fall-times on the other hand, showed a much higher cut-off frequency of 16 MHz. The electro-optic, all-fiber switch was also employed to select single pulses at 1 MHz repetition rate out of a 7 MHz train of pulses. Additionally, simulations using the finite element method were performed in order to gain insight and to explain the underlying processes of the observed response of a long-period grating written in a 2-hole fiber with electrodes, when applying HV-pulses to one of these. The thesis shows that the studied fiber-components show great potential of becoming complementary devices with high damage threshold for all-fiber laser applications in the future. QC 20121129</p

Multi-angle Oblique Optical Coherence Tomography

Optical Coherence Tomography (OCT) is a non-invasive high-resolutionmethod for measuring the reectance of scattering media in 1/2/3D, e.g.skin. The method has been used in a number of dierent medical elds andfor measurement of tissue optical properties.The software developed in this thesis is able to display features hidden ina shadowed volume by adding multiple OCT measurements taken at obliqueangles, a technique here called Multiple-Angle Oblique Optical CoherenceTomography (MAO-OCT).Three dierent objects with were measured at 5 to 9 angles. The measurementswere automatically and manually aligned in the software. They werealso tested with 6 dierent high pass intensity lters (HPIF) and reduced insize using 4 dierent methods to speed up calculations.The software's automatic alignment was tested with one tilted computergenerated test at 9 angles and with 5 dierent shadow strengths.With MAO-OCT it is possible to remove some eects of shadows in OCT,though it comes with a cost of reduced sharpness. The errors depend muchon the dierences in index of refraction in the sample.The software managed to automatically align 90% of the articial measurements,and 60% of the OCT measurements. The shadow strength andthe resize method had no noticeable eect on the automatic alignment of themeasurements

Application of Laser-Ultrasonics for Evaluating Textures and Anisotropy

Various approaches are reviewed for determining elastic anisotropy and its coupling to crystallographic texture, with special reference to ultrasonic measurements. Two new methods are described for measuring the anisotropy of P-wave velocity using laser-ultrasonics. Making measurements across the diameter of a cylindrical specimen as it is rotated makes it possible to maintain a very constant known path length. This permits extremely accurate measurements with a precision of better than 0.01%. Results on 316 stainless steel in different conditions are compared with calculated values obtained from EBSD textures together with measured densities and crystalline coefficients from the literature. Excellent agreement is obtained when applying the Hill geometrical average procedure. A similar approach is adopted to measure the variation of wave velocity in a martensitic steel, after tempering at a range of temperatures. Changes in the anisotropy associated with thermal softening are discussed. The second method uses Galvano mirrors to steer the generating laser to different positions over a sheet surface, allowing wave velocities to be determined along different directions in the anisotropic material

Nondestructive Evaluation with Laser Ultrasound of Powder Bed Fusion Printed Metal Parts

Introduction/Purpose Many of the main advantages of 3D printing metal components, for example the possibility to manufacture components of high geometriccomplexity in small series, typically make the nondestructive quality control difficult and resource intense. A number of published studies haveproposed in-process quality control of the component, as it is built layer by layer, as a possible general approach solution to this difficulty. Previousstudies have also indicated that the non-contact nondestructive testing method laser ultrasound might be an applicable method to conduct such anin-process nondestructive evaluation of 3D printed components. Methods In this work laser ultrasonic nondestructive evaluation of both electron beam and laser beam powder bed fusion printed metal parts isdemonstrated. Nickel-base and Stainless Steel samples are evaluated both from a machined surface and, in order to simulate the in-process setup,from the as-printed top surface. Results The laser ultrasonic evaluation results are compared to results from other material characterization methods. Designed artificial defects as well asprocess material anomalies could be detected with the proposed laser ultrasonic evaluation, both when the evaluation was performed from the asprintedtop surface as well as from the machined surface. Conclusions We conclude that laser ultrasound can be utilized to detect material anomalies of interest in powder bed fusion printed metal parts. Furtherresearch is required in order to better understand and improve the capability and reliability of the nondestructive evaluation method.QC 20190930</p

Diamond waveguides for mid-IR sensing

QC 20150107</p

Nondestructive Evaluation with Laser Ultrasound of Powder Bed Fusion Printed Metal

Many of the main advantages of 3D printing metal components, for example the possibility to manufacture parts of high geometric complexity in small series, typically make the nondestructive quality control difficult and resource intense. A number of published studies have proposed in-process nondestructive evaluation of the printed material, as it is built layer by layer, as a possible general approach solution to this difficulty. Previous studies have also indicated that the non-contact nondestructive testing method laser ultrasound might be an applicable method to conduct such an in-process nondestructive evaluation of 3D printed parts. Potential pros of such an ultrasonic based evaluation, as compared to more process monitoring like approaches (e.g. acoustic emission from the printing process) would for example be increased defect characterization capabilities.In this work laser ultrasonic nondestructive evaluation of both electron beam and laser beam powder bed fusion printed metal is demonstrated. Nickel-base and Stainless Steel samples are evaluated both from a machined surface and, in order to simulate the in-process setup, from the as-printed top surface.The laser ultrasonic evaluation results are then compared to results from other material characterization methods, such as light optical microscopy and X-ray inspection. Designed artificial defects as well as process material anomalies could be detected with the proposed laser ultrasonic evaluation. In some cases material defects could be detected also when the laser ultrasonic evaluation was performed from the as-printed top surface.Our results are similar to other studies that have been reported on the subject: laser ultrasound can be utilized to detect material anomalies of interest in powder bed fusion printed metal material. Further research is required in order to better understand and improve the capability and reliability of the nondestructive evaluation method.QC 20191001</p