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Objective: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA)., Methods: Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed., Results: One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%., Conclusion: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation., (© 2018, American College of Rheumatology.)

Objective: To determine whether Calmer Life (CL) improved worry, generalized anxiety disorder-related (GAD-related) symptoms, anxiety, depression, sleep, trauma-related symptoms, functional status, and quality of life better than Enhanced Community Care with Resource Counseling (ECC-RC) at 6 months and 9 months., Methods: A randomized, controlled, comparative-effectiveness study involving underserved, low-income, mostly minority neighborhoods in Houston, Texas, looked at individuals ≥50 with significant worry and interest in psychosocial treatment. Interventions were CL, cognitive behavioral therapy with resource counseling, facilitation of communication with primary care providers about worry/anxiety, integration of religion/spirituality, person-centered skill content and delivery and nontraditional community providers, ECC-RC, and enhanced standard community-based information/ resource counseling addressing basic unmet and mental health needs. Primary outcomes were worry and GAD-related symptom severity. Secondary outcomes were anxiety, depression, sleep difficulties, trauma-related symptoms, functional status, quality of life, service use and satisfaction., Results: Similar, moderate improvements followed CL and ECC-RC on worry, GAD-related symptoms, anxiety, depression, sleep, trauma-related symptoms, and mental health quality of life at 6 and 9 months, but with symptoms at both times and higher satisfaction with CL at both. Fewer ECC-RC participants reported a hospital admission in the prior 3 months than those in CL at 6 and 9 months; at 9 months, fewer reported a visit with a provider in the previous 3 months., Conclusion: Both interventions showed similar improvements at 6 and 9 months, but symptoms remained that might require care. Either intervention or a combination may be useful for low-income older adults with identified worry/anxiety., (Published by Elsevier Inc.)

Objective: Anxiety is common among older adults and is associated with multiple negative outcomes. Late-life anxiety is usually unrecognized by providers and undertreated, although evidence supports the effectiveness of psychosocial treatment. Access to mental health care is especially poor among African American seniors. New treatment models are needed to expand the reach of mental health care to minority elders., Methods: Our article outlines a study designed to test the effectiveness and implementation potential of Calmer Life (CL), a community-based, person-centered, flexible and culturally tailored intervention for late-life anxiety and worry, offered in low-income, mental health-underserved and predominantly African American communities. CL is skills-based, but also includes resource counseling and an option to integrate religion/spirituality. The study population includes individuals 50 years of age and older who are experiencing high levels of worry. The program was developed in the context of a community-academic partnership with organizations that provide services for seniors in underserved communities, and it trains nontraditional community providers to deliver the intervention., Results: Study progress to date, challenges, and lessons learned are discussed. Data collection is ongoing, and study findings will be available in late 2017., Conclusions: CL will offer valuable information to help expand the reach of anxiety treatment among minority seniors living in underserved neighborhoods.

Objective: Determine predictors of reduced worry and anxiety for older adults participating in the pilot phase of Calmer Life, a modular, personalized cognitive-behavioral treatment for worry., Methods: Underserved adults (N = 54) over age 50 participated. Therapists were either experts (Ph.D. or Master's) or nonexpert providers (case managers, community health workers, and bachelor's level). Participants completed the Penn State Worry Questionnaire-Abbreviated (PSWQ-A) and the Geriatric Anxiety Inventory-Short Form (GAI-SF) before treatment and at 3 months., Results: Demographic and clinical variables were individually entered into separate regression equations, controlling for pretreatment scores, to determine their associations with post-treatment 1) PSWQ-A and 2) GAI-SF scores. Only younger age and African American race were significant (p < .05) univariate predictors of higher post-treatment PSWQ-A scores. African American race was also a significant predictor of higher post-treatment GAI-SF scores., Conclusions: African American participants had higher post-treatment PSWQ-A and GAI-SF scores than White and Hispanic participants. Younger age was also associated with more severe PSWQ-A post-treatment scores., Clinical Implications: Younger participants may experience additional stressors (e.g., caregiving, working) compared with older participants. Smaller decreases in anxiety in African Americans point to the need for continued focus and additional modification of interventions.

Platinum and iridium are rare and expensive noble metals that are used as catalysts for different sectors including in heterogeneous chemical automotive emission catalysis and electrochemical energy conversion. Nickel and its alloys are promising materials to substitute noble metals. Nickel based materials are cost-effective with good availability and show comparable catalytic performances. The nickel-molybdenum system is a very interesting alternative to platinum in water electrolysis. We produced ligand-free nickel-molybdenum nanoparticles by laser ablation in water and acetone. Our results show that segregated particles were formed in water due to the oxidation of the metals. X-ray diffraction shows a significant change in the lattice parameter due to a diffusion of molybdenum atoms into the nickel lattice with increasing activity in the electrochemical oxygen evolution reaction. Even though the solubility of molecular oxygen in acetone is higher than in water, there were no oxides and a more homogeneous metal distribution in the particles in acetone as seen by TEM-EDX. This showed that dissolved molecular oxygen does not control oxide formation. Overall, the laser ablation of pressed micro particulate mixtures in liquids offers a combinational synthesis approach that allows the screening of alloy nanoparticles for catalytic testing and can convert micro-mixtures into nano-alloys., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pulsed laser ablation in liquids (PLAL) is a multiscale process, involving multiple mutually interacting phenomena. In order to synthesize nanoparticles with well-defined properties it is important to understand the dynamics of the underlying structure evolution. We use visible-light stroboscopic imaging and X-ray radiography to investigate the dynamics occurring during PLAL of silver and gold on a macroscopic scale, whilst X-ray small angle scattering is utilized to deepen the understanding on particle genesis. By comparing our results with earlier reports we can elucidate the role of the cavitation bubble. We find that symmetry breaking at the liquid-solid interface is a critical factor for bubble motion and that the bubble motion acts on the particle distribution as confinement and retraction force to create secondary agglomerates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pulsed laser ablation in liquid (PLAL) has proven its usefulness as a nanoparticle (NP) synthesis method alternative to traditional chemical reduction methods, where the absence of any molecular ligands or residual reactants makes laser-generated nanoparticles ideal reference materials for charge-transfer experiments. We synthesized additive-free platinum nanoparticles by PLAL and in-situ characterized their interaction with H2O, sodium phosphate buffer, and sodium citrate as well as a TiO2 support by X-ray absorption fine structure (XAFS), i.e., X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS). Differences in the white-line intensity among the colloidal particles in the three liquids indicate that the respective NP-solvent interaction varies in strength. The ions added ex situ diffuse through the particles' electric double layer and interact electrostatically with the Stern plane. Consequently, these ions weaken the interaction of the functional OH groups that are bound to the partially oxidized platinum surfaces and cause their partial reduction. Comparing XAFS spectra of laser-generated Pt NPs in citrate with wet-chemically synthesized ones (both ligand-covered) indicates different types of Pt-O bonds: a Pt(IV)O2 type in the case of wet-chemical NPs and a Pt(II)O type in the case of laser-generated NPs. A comparison of unsupported laser-generated platinum NPs in H2O with TiO2-supported ones shows no white-line intensity differences and also an identical number of Pt-O bonds in both cases. This suggests that in the deposition process at least part of the double-layer coating stays intact and that the ligand-free Pt particle properties are preserved in the TiO2-supported Pt particles, relevant for heterogeneous catalysis.

Objectives: To evaluate the feasibility of the Calmer Life and Enhanced Community Care interventions delivered by community and expert providers and test their preliminary effectiveness on worry, generalized anxiety disorder (GAD) severity, anxiety, depression, sleep, health-related quality of life, and satisfaction., Design: Small randomized trial, with measurements at baseline and 3 months., Setting: Underserved, low-income, mostly minority communities in Houston, TX., Participants: Forty underserved adults 50 years and older, with significant worry and principal or coprincipal GAD or anxiety disorder not otherwise specified., Intervention: Combination of person-centered, flexible skills training to reduce worry; resource counseling to target unmet basic needs; and facilitation of communication with primary care providers developed through a community-academic partnership with social service and faith-based organizations. Religion/spirituality may be incorporated., Primary Outcomes: worry (Penn State Worry Questionnaire-Abbreviated), GAD severity (GAD-7), anxiety (Geriatric Anxiety Inventory-Short Form)., Secondary Outcomes: depression (Patient Health Questionnaire-8 and Geriatric Depression Scale-Short Form), sleep (Insomnia Severity Index), health-related quality of life (12-item Medical Outcomes Study Short Form), satisfaction (Client Satisfaction Questionnaire and exit interviews)., Results: Provider training was valid; mean ratings for community providers were well above average, with none less than adequate. Reach was excellent. Participants receiving the Calmer Life intervention had greater improvement in GAD severity and depression than those receiving Enhanced Community Care. Satisfaction with both treatments was equivalent., Conclusions: A larger comparative-effectiveness trial needs to examine outcomes following the Calmer Life intervention relative to standard community-based care and to evaluate more fully issues of implementation potential., (Published by Elsevier Inc.)

Laser-induced cavitation has mostly been studied in bulk liquid or at a two-dimensional wall, although target shapes for the particle synthesis may strongly affect bubble dynamics and interfere with particle productivity. We investigated the dynamics of the cavitation bubble induced by pulsed-laser ablation in liquid for different target geometries with high-speed laser microsecond videography and focus on the collapse behaviour. This method enables us observations in a high time resolution (intervals of 1 μs) and single-pulse experiments. Further, we analyzed the nanoparticle productivity, the sizes of the synthesized nanoparticles and the evolution of the bubble volume for each different target shape and geometry. For the ablation of metal (Ag, Cu, Ni) wire tips a springboard-like behaviour after the first collapse is observed which can be correlated with vertical projectile motion. Its turbulent friction in the liquid causes a very efficient transport and movement of the bubble and ablated material into the bulk liquid and prevents particle redeposition. This effect is influenced by the degree of freedom of the wire as well as the material properties and dimensions, especially the Young's modulus. The most efficient and largest bubble movement away from the wire was observed for a thin (500 μm) silver wire with velocities up to 19.8 m s(-1) and for materials with a small Young's modulus and flexural rigidity. We suggest that these observations may contribute to upscaling strategies and increase of particle yield towards large synthesis of colloids based on targets that may continuously be fed.

This work highlights a strategy for the one-step synthesis of FeAu nanoparticles by the pulsed laser ablation of alloy targets in the presence of different solvents. This method allows particle generation without the use of additional chemicals; hence, solvent-metal interactions could be studied without cross effects from organic surface ligands. A detailed analysis of generated particles via transmission electron microscopy in combination with EDX elemental mapping could conclusively verify that the nature of the used solvent governs the internal phase structure of the formed nanoparticles. In the presence of acetone or methyl methacrylate, a gold shell covering a non-oxidized iron core was formed, whereas in aqueous media, an Au core with an Fe3O4 shell was generated. This core-shell morphology was the predominant species found in >90% of the examined nanoparticles. These findings indicate that fundamental chemical interactions between the nanoparticle surface and the solvent significantly contribute to phase segregation and elemental distribution in FeAu nanoparticles. A consecutive analysis of resulting Fe@Au core-shell nanoparticles revealed outstanding oxidation resistance and fair magnetic and optical properties. In particular, the combination of these features with high stability magnetism and plasmonics may create new opportunities for this hybrid material in imaging applications.

Pulsed-laser assisted nanoparticle synthesis in liquids (PLAL) is a versatile tool for nanoparticle synthesis. However, fundamental aspects of structure formation during PLAL are presently poorly understood. We analyse the spatio-temporal kinetics during PLAL by means of fast X-ray radiography (XR) and scanning small-angle X-ray scattering (SAXS), which permits us to probe the process on length scales from nanometers to millimeters with microsecond temporal resolution. We find that the global structural evolution, such as the dynamics of the vapor bubble can be correlated to the locus and evolution of silver nanoparticles. The bubble plays an important role in particle formation, as it confines the primary particles and redeposits them to the substrate. Agglomeration takes place for the confined particles in the second bubble. Additionally, upon the collapse of the second bubble a jet of confined material is ejected perpendicularly to the surface. We hypothesize that these kinetics influence the final particle size distribution and determine the quality of the resulting colloids, such as polydispersity and modality through the interplay between particle cloud compression and particle release into the liquid.

Adsorption of colloidal nanoparticles to surfaces and supports is a convenient approach to heterogeneous catalysts, polymer additives, or wastewater treatment. We investigated the adsorption efficiency of laser-generated and initially ligand-free platinum nanoparticles to TiO2 supports as a function of pH, ionic strength, and ligand surface coverage. The nanoparticle adsorption is dominantly controlled by electrostatic interactions: if the pH of the suspension is between the isoelectric point of the nanoparticles and the support, nanoparticles are adsorbed and transfer a net charge to the support. This charge-driven adsorption is not affected by steric repulsion due to various ligands attached to the nanoparticle surface. In addition to electrostatic interactions, colloidal stability given by moderate ionic strengths and pH values above the isoelectric point of nanoparticles are prerequisites for colloidal deposition.

Surface pre-endothelialization is a promising approach to improve the hemocompatibility of implants, medical devices, and artificial organs. To promote the adhesive property of thermoplastic polyurethane (TPU) for endothelial cells (ECs), up to 1 wt % of gold (Au) or platinum (Pt) nanoparticles, fabricated by pulsed laser ablation in polymer solution, were embedded into the polymer matrix. The analysis of these nanocomposites showed a homogenous dispersion of the nanoparticles, with average diameters of 7 nm for Au or 9 nm for Pt. A dose-dependent effect was found when ECs were seeded onto nanocomposites comprising different nanoparticle concentrations, resulting in a fivefold improvement of proliferation at 0.1 wt % nanoparticle load. This effect was associated with a nanoparticle concentration-dependent hydrophilicity and negative charge of the nanocomposite. In dynamic flow tests, nanocomposites containing 0.1 wt % Au or Pt nanoparticles allowed for the generation of a confluent and resistant EC layer. Real-time polymerase chain reaction quantification of specific markers for EC activation indicated that ECs cultivated on nanocomposites remain in an inactivated, nonthrombogenic and noninflammatory state; however, maintain the ability to trigger an inflammatory response upon stimulation. These findings were confirmed by a platelet and leukocyte adhesion assay. The results of this study suggest the possible applicability of TPU nanocomposites, containing 0.1 wt % Au or Pt nanoparticles, for the generation of pre-endothelialized surfaces of medical devices., (© 2013 Wiley Periodicals, Inc.)

Using wires of defined diameters instead of a planar target for pulsed laser ablation in liquid results in significant increase of ablation efficiency and nanoparticle productivity up to a factor of 15. We identified several competitive phenomena based on thermal conductivity, reflectivity and cavitation bubble shape that affect the ablation efficiency when the geometry of the target is changed. On the basis of the obtained results, this work represents an intriguing starting point for further developments related to the up-scaling of pulsed laser ablation in liquid environments at the industrial level.

The formation of nanoparticles within the laser-induced cavitation bubble is studied in situ using small angle X-ray scattering with high spatiotemporal resolution. Directly after laser ablation, two different particle fractions consisting of compact primary particles of 8-10 nm size and agglomerates of 40-60 nm size are formed. The abundance of these species is strongly influenced by the dynamics of the oscillating cavitation bubble. Primary particle mass is most abundant during maximal expansion of the first bubble and reappears a little weaker in the rebound. In contrast to this, the mass abundance of agglomerates is relatively low in the first bubble but strongly increases during first bubble collapse and following rebound. Although most of the ablated material is trapped inside the bubble and follows its oscillation, a minor fraction of both species could be detected outside the cavitation bubble even before its final collapse.

Although the first nanoseconds to microseconds rule the resulting process yield of laser ablation in liquid, a comprehensive view involving combination of time-resolved measurement techniques is still lacking. In this paper, fundamental aspects of laser ablation of metals in water during the production of nanoparticles are discussed. Three fast diagnostic methods have been applied simultaneously. These are Optical Emission Spectroscopy for the plasma characterization, fast shadowgraph for plasma and cavitation bubble dynamics and laser scattering for the mechanisms of delivery of the produced materials in the liquid. Moreover, in order to validate the discussion, the effect on cavitation dynamics of the ablation of bulk and wire-shaped targets has been investigated together with the relative nanoparticles production yield. Unusual arrow-bow ejection phenomena between the cavitation bubble and the wire result in suppressed material back-deposition, causing efficient ejection of ablated matter into the liquid. The presented nanosecond and microsecond-resolved analysis allows estimating the timescale and role of the basic mechanisms involved in laser ablation in liquids as well as the thermodynamic characteristics of the processes.

We report on a retrospective study of 16 rheumatoid arthritis (RA) patients with reduction in size of pulmonary and peripheral rheumatoid nodules following treatment with rituximab (RTX). The 8 female and 8 male patients had an average disease duration of 12.2 years, 88 % were anti-CCP positive and 94 % seropositive. Prior treatment included an average of 2.9 DMARD and 1.4 biological therapies. On average 6.1 rheumatoid nodules were found on hands and elbows and 5 patients had pulmonary nodules. In 6 out of 16 patients the nodules disappeared completely, in 2 patients a pulmonary nodule disappeared. In 10 out of 16 patients the size of the nodules decreased by approximately 50%, 1 out of the 16 patients with significant increase in size and number of nodules prior to RTX therapy showed a reduction in size but no new nodules occurred. The regression in size of the nodules occurred 34.2±39.1 weeks following RTX therapy, correlating with 1.3±0.59 RTX infusion cycles. Overall, increases in size or new nodules were reported in none of the patients. One nodule examined histologically following RTX therapy did not show any specific differences. RTX may lead to a marked reduction in size of rheumatoid nodules in RA patients. More studies are necessary to confirm whether this is an RTX-specific effect.

Residual ligands from colloidal synthesis of nanoparticles influence adsorption of nanoparticles to supports and may complicate fabrication of nanoparticle-decorated microparticles. In this work, we studied the adsorption of completely ligand-free metal nanoparticles and controlled ligand-functionalized nanoparticles to chemically inert microparticle supports. Adsorption of ligand-free silver nanoparticles to barium sulfate microparticle supports is a quantitative, nonreversible process following Freundlich adsorption isotherm. However, adsorption efficiency is very sensitive to ligand concentration applied during laser-based synthesis of silver nanoparticles: exceeding a specific threshold concentration of 50 μmol/L citrate equal to a nanoparticle ligand surface coverage of about 50%, results in an almost complete prevention of nanoparticle adsorption because of electrosteric repulsion by ligand shell. Laser-based synthesis of nanoparticle-decorated microparticles is demonstrated with a variety of metal nanoparticles (Ag, Au, Pt, Fe) and supporting microparticles (calcium phosphate, titanium dioxide, barium sulfate) with application potential in heterogeneous catalysis or biomedicine where ligand control offers extra value, like enhanced catalytic activity or biocompatibility., (© 2012 American Chemical Society)

Biofunctionalized silicon quantum dots were prepared through a one step strategy avoiding the use of chemical precursors. UV-Vis spectroscopy, Raman spectroscopy and HAADF-STEM prove oligonucleotide conjugation to the surface of silicon nanoparticle with an average size of 4 nm. The nanoparticle size results from the size-quenching effect during in situ conjugation. Photoemissive properties, conjugation efficiency and stability of these pure colloids were studied and demonstrate the bio-application potential, e.g. for nucleic acid vector delivery with semiconducting, biocompatible nanoparticles., (This journal is © The Royal Society of Chemistry 2012)

Metal ion release kinetics from silver and copper nanoparticle silicone composites generated by laser ablation in liquids are investigated. The metal ion transport mechanism is studied by using different model equations and their fit to experimental data. Results indicate that during the first 30 days of immersion, Fickian diffusion is the dominant transport mechanism. After this time period, the oxidation and dissolution of nanoparticles from the bulk determine the ion release. This second mechanism is very slow since the dissolution of the nanoparticle is found to be anisotropic. Silver ion release profile is best described by pseudo-first order exponential equation. Copper ion release profile is best described by a second order exponential equation. For practical purposes, the in vitro release characteristics of the bioactive metal ions are evaluated as a function of nanoparticle loading density, the chemistry and the texture of the silicone. Based on the proposed two-step release model, a prediction of the release characteristics over a time course of 84 days is possible and a long-term ion release could be demonstrated., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Charged Pt-Ir alloy nanoparticles are generated through femtosecond laser ablation of a Pt₉Ir target in acetone without using chemical precursors or stabilizing agents. Preservation of the target's stoichiometry in the colloidal nanoparticles is confirmed by transmission electron microscopy (TEM)-energy-dispersive x-ray spectroscopy (EDX), high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM)-EDX elemental maps, high resolution TEM and selected area electron diffraction (SAED) measurements. Results are discussed with reference to thermophysical properties and the phase diagram. The nanoparticles show a lognormal size distribution with a mean Feret particle size of 26 nm. The zeta potential of -45 mV indicates high stability of the colloid with a hydrodynamic diameter of 63 nm. The charge of the particles enables electrophoretic deposition of nanoparticles, creating nanoscale roughness on three-dimensional PtIr neural electrodes within a minute. In contrast to coating with Pt or Ir oxides, this method allows modification of the surface roughness without changing the chemical composition of PtIr.

The crucial step in the production of solid nanocomposites is the uniform embedding of nanoparticles into the polymer matrix, since the colloidal properties or specific physical properties are very sensitive to particle dispersion within the nanocomposite. Therefore, we studied a laser-based generation method of a nanocomposite which enables us to control the agglomeration of nanoparticles and to increase the single particle dispersion within polyurethane. For this purpose, we ablated targets of silver and copper inside a polymer-doped solution of tetrahydrofuran by a picosecond laser (using a pulse energy of 125 μJ at 33.3 kHz repetition rate) and hardened the resulting colloids into solid polymers. Electron microscopy of these nanocomposites revealed that primary particle size, agglomerate size and particle dispersion strongly depend on concentration of the polyurethane added before laser ablation. 0.3 wt% polyurethane is the optimal polymer concentration to produce nanocomposites with improved particle dispersion and adequate productivity. Lower polyurethane concentration results in agglomeration whereas higher concentration reduces the production rate significantly. The following evaporation step did not change the distribution of the nanocomposite inside the polyurethane matrix. Hence, the in situ coating of nanoparticles with polyurethane during laser ablation enables simple integration into the structural analogue polymer matrix without additives. Furthermore, it was possible to injection mold these in situ-stabilized nanocomposites without affecting particle dispersion. This clarifies that sufficient in situ stabilization during laser ablation in polymer solution is able to prevent agglomeration even in a hot polymer melt.

Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.

The generation of nonoxidized magnetic alloy nanoparticles is still a challenge using conventional chemical reduction methods. However, because these nanoparticles are currently attracting much attention, alternative methods are required. In this context, the applicability of femtosecond laser ablation, which has evolved as a powerful tool for the generation of colloidal metal nanoparticles, has been investigated using the example of Ni(48)Fe(52) and Sm(2)Co(17) ablation in cyclopentanone. Besides stability and size measurements, the focus has been placed on the analysis of the elemental composition of nanoparticles, which proved the preservation of the stoichiometry of the target in Ni-Fe nanoparticles but not in Sm-Co. It is assumed that this is due to a greater difference in the heat of evaporation of the bulk alloy components in Sm-Co than in Ni-Fe. Hence, the successful generation of magnetic alloy nanoparticles is possible for alloys composed of elements with similar heats of evaporation. This one-step approach allows the fabrication of nanomagnetic polymer composites (e.g., with application prospects in microtechnology such as microactuators).

Ultrafast electronic excitation transfer (EET) followed by structural and vibrational relaxation (VER) of the acceptor have been characterised using transient absorption and transient lens techniques.

This study evaluated the Penn State Worry Questionnaire, Penn State Worry Questionnaire-Abbreviated, and the Generalized Anxiety Disorder Questionnaire-IV for identifying generalized anxiety disorder in older medical patients. Participants were 191 of 281 patients screened for a clinical trial evaluating cognitive-behavior treatment, n = 110 with generalized anxiety disorder, 81 without. Participants completed the Penn State Worry Questionnaire and Generalized Anxiety Disorder Questionnaire-IV at pretreatment. Kappa coefficients estimated agreement with the Structured Clinical Interview for Diagnosis. Receiver operating characteristic curves compared sensitivity and specificity of self-report measures. The Penn State Worry Questionnaire (cutoff = 50) provided the strongest prediction of generalized anxiety disorder (sensitivity, 76%; specificity, 73%; 75% correctly classified; kappa = .49. Item 2 of the Generalized Anxiety Disorder Questionnaire-IV demonstrated comparable accuracy. The Penn State Worry Questionnaire, Generalized Anxiety Disorder Questionnaire-IV, and briefer versions of these measures may be useful in identifying late-life generalized anxiety disorder in medical settings.

The density dependence of diiodomethane photoinduced isomerization in supercritical (sc) CO2, CHF3, and C2H6 was investigated by transient absorption spectroscopy, covering a fluid density range from 0.7 to 2.5 (in reduced units). The solvent-caged photoproduct iso-diiodomethane is formed even at the lowest density, and its yield increases about 4-fold over the whole range. At the same time, isomer formation rate constants increase by roughly an order of magnitude and show little variation between CO2, C2H6, and CHF3. Furthermore, the formation rate constant decreases significantly with increasing excitation energy. We propose an isomer formation mechanism involving a rapidly established preequilibrium between a solvent-caged iodine atom-methyliodide radical pair and a loosely bound iodine-methyliodide radical complex, from which the reaction subsequently proceeds to the isomer. The latter step seems to be controlled by collisional stabilization of the initially hot radical moiety, as the formation rate constant increases linearly with sc solvent viscosity. The model predicts a quadratic dependence of relative isomer yield on fluid density. A corresponding correlation is found with the local fluid density, calculated via solute-solvent radial distribution functions obtained from molecular dynamics (MD) simulations.

Objective: The authors present data from a pilot research program initiated to develop, refine, and test the outcomes of CBT-GAD/PC, a version of cognitive-behavior therapy (CBT) that targets the needs of older adults with generalized anxiety disorder (GAD) in primary care (PC)., Methods: The study involved a small, randomized clinical trial comparing the impact of CBT-GAD/PC to usual care (UC) in a sample of 12 older medical patients with GAD., Results: Outcome data suggested significant improvements in worry and depression after CBT-GAD/PC, relative to UC., Conclusion: Authors discuss results in terms of the "real-world" applicability of this treatment for late-life GAD, and present implications for future research.

The surface protein ActA of the pathogenic bacterium Listeria monocytogenes induces actin-driven movement of bacteria in the cytoplasm of infected host cells and serves as a model for actin-based motility in general. We generated and purified soluble recombinant fragments of ActA and assessed their ability to interact with the acidic phospholipids phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, both implicated in the regulation of actin polymerization. Purified ActA consisted of biologically active, elongated molecules with an alpha-helix and beta-sheet content of 11 and 32%, respectively. In the presence of either phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate, but not phosphatidylcholine, ActA molecules underwent a structural change that raised the alpha-helix content to 19% and lowered the beta-sheet content to 27%. Co-sedimentation experiments with phosphatidylcholine vesicles containing different acidic phospholipids demonstrated that ActA binds preferentially to D-3 phosphoinositides. The D-3 phosphoinositide binding activity was mapped to a small subregion in the N-terminal domain of ActA. This subregion comprised 19 amino acids and showed homology to cecropins. In addition, we found that amino acids 33 to 74 of ActA mediated actin binding by the whole, folded ActA molecule. These findings shed new light on ActA function.

Twenty-seven patients with polymyalgia rheumatica were treated with methotrexate. In comparison with 295 patients with other inflammatory rheumatic diseases under methotrexate therapy, a favorable rate of therapeutic effect and a low rate of side-effects could be observed. Remissions appeared in the mean after 6 months (1-24 months). Therapeutic failures (1/27) or side-effects inducing breaking off the therapy (2/27) were rare. Methotrexate seems to be a useful possibility to supplement the corticosteroid therapy of polymyalgia rheumatica.

Manifestations of polymyalgia rheumatica in 100 ambulatory patients of an internistic, rheumatological specialist's practice were investigated. In this group of patients, both the clinical course of the disease and its prognosis were found to be more benign than is commonly reported in the literature. Thus, for example, temporal arteritis was found in only three of the one hundred patients. Not all of the patients were found to have the markedly elevated ESR normally considered to be typical. For this reason, to establish inflammatory activity, in addition to ESR, C-reactive protein (CRP) should also be determined in order to ensure that atypical forms with less marked signs of inflammation are not overlooked. Thirty of the 100 patients reported possible triggering life events.

The significance of acral nodulosis under methotrexate therapy is still controversial. Among patients with rheumatoid arthritis and methotrexate therapy this manifestation could be observed in 8/163 (5%). All cases were seropositive and already treated with other LAAD. Patients with other inflammatory rheumatic diseases under methotrexate therapy (n = 83) did not develop this nodulosis. The acral nodulosis is interpreted as a typical side-effect of methotrexate only in patients with rheumatoid arthritis. Histopathologically, these nodules do not differ from the typical rheumatoid nodule.

From January 1986 through January 1989 69 adult patients received bone marrow transplants--20 with autologous, and 49 with allogeneic bone marrow. Ten patients after autologous and 33 patients after allogeneic transplantation (TX) could be examined for rheumatological complaints. None of the patients after autologous TX displayed rheumatological manifestations; 8/33 patients after allogeneic TX developed bone necrosis and they had to be treated for several months with high daily doses of prednisolon (mean: 55 mg/day). In 18/33 patients an oligoarthropathy of large joints could be observed after a significant reduction of prednisolon dosage over a period of 5 months. In addition 15/18 of these patients later developed a chronic g-v-h-disease. The TX arthropathy may be induced by cortico-steroid therapy (resp. reduction), but most important, it is a clinical sign for an imminent chronic g-v-h-disease.

67 patients with ankylosing spondylitis (AS) were tissue-typed for HLA-A, -B and -C antigens. HLA-Bw62 was found in 6 of 13 (46%) HLA-B27 negative patients, compared to 9% in HLA-B27 positive AS (p greater than 0.01) and 10% in healthy blood donors (p greater than 0.001). HLA-Bw62, a split of the previous HLA-B15, belongs to the HLA-Bw35 CREG antigens, 11 of 13 (85%) of HLA-B27 negative patients had an HLA-Bw35 CREG antigen. The present results are interpreted as an indication of a direct involvement of the HLA-B locus in the pathogenesis of AS.

The etiology of inflammatory rheumatic diseases is unknown. The hypothesis, that bacteriae may play a part in the induction of a rheumatic synovialitis is further substantiated by the detection of Endotoxin (Lipid A) in the synovial membranes of five of eleven patients with early synovitis (disease duration shorter than 6 months) by using anti Lipid A monoclonal antibodies. Endotoxin (Lipid A) is a component of gram-negative bacteriae and Chlamydiae. It is a potent immunogen, and could be the link between infection of the gut or the urogenital system and the rheumatic synovialitis.

Among 86 patients selected as possibly having ankylosing spondylitis because of clinical symptoms and radiologically normal sacroiliac joints. HLA-B27 was positive in 41%. Four years later a representative sample of 38 individuals were re-examined and radiographed. HLA-B27 positive patients developed sacroiliitis as defined by radiological criteria twice as often (P less than 0.05). They also showed increased uptake of technetium 99 m upon quantitative scintigraphy with a region of interest method and more often probable or definite ankylosing spondylitis as defined by the New York criteria. Further differences between the HLA-B27 positive and negative follow-up groups concerned the frequency of clinical symptoms and peripheral arthritis. It is suggested that HLA-B27 typing may be helpful both in diagnosis and in judging the prognosis of possible or abortive ankylosing spondylitis.

Sterno-costo-hyperostosis is an inflammatory rheumatic disease which is associated to pustulosis palmaris et plantaris. The origin of this disorder is unknown. We described the appearance as a "reactive" fibromatosis in connection with a hyperostosis of a clavicle, which could be demonstrated in a biopsy-probe and by NMR-technique.

We measured the amount of plasma endotoxin in 95 patients with inflammatory rheumatic diseases (42 with ankylosing spondylitis; 12 with possible ankylosing spondylitis; 41 with rheumatoid arthritis) and in 16 patients with Crohn's disease with a quantitative Limulus assay. Significantly increased mean values were found in inflammatory rheumatic diseases and in Crohn's disease. Between 31% and 50% of the patients had endotoxin values higher than 10 pg/ml--none of the controls had such values. Patients on regular treatment with NSAIDS had higher amounts of endotoxin again. From our results we discuss an intestinal involvement in inflammatory rheumatic diseases. An inflammation of the gut with an increased permeability seems to be responsible for the raised plasma endotoxin levels compared to healthy controls. NSAIDs probably contribute to the increased permeability of the gut.

Yttrium-90 radiosynoviorthesis of the knee joint in rheumatic inflammatory diseases shows favourable results. Because of the supposed exposure of the patients gonads, Yttrium synoviorthesis has rarely been performed in patients below the age of 40. Scintigraphic studies in 20 patients with rheumatoid arthritis showed no significant leakage of the radionuclide from the knee joint. Gamma camera measurements both phantom and in vivo in the regions of ovary and testes revealed a local dose of 1.05 microGy/MBq (3.9 mrd/mCi) or 1.1 microGy/MBq (4.1 mrd/mCi) of the injected radioactivity. Calculation of the maximum possible load of the gonads, supposing even total leakage of the injected 90-Yttrium from the knee joint, yielded a maximum possible dose of 6 mGy (600 mrd). We conclude from these studies and calculations that Yttrium-90 synoviorthesis of the knee joint can safely be carried out in patients below the age of 40.

Sonography and NMR imaging of the knee joint make it possible to obtain a visual representation of the thickened synovial membrane occurring in patients with rheumatoid gonarthritis, even before inflammatory deformation is radiologically detectable. Both methods can expose effusions and Baker's cysts. In NMR imaging, an indication of the inflammatory genesis can be obtained from the extended relaxation time T1. Due to the good representation of soft tissues, prognostic evidence may be gained of whether a mainly exudative or proliferative form is present.