Radiology volunteers to support a breast cancer screening program in Peru: Description of the project, preliminary results, and impressions.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Voluntariado radiológico para apoyar un programa de detección precoz del cáncer de mama en Perú: descripción del proyecto, presentación de los primeros resultados e impresiones / Radiology volunteers to support a breast cancer screening program in Peru: description of the project, preliminary results, and impressions

El cáncer de mama es el segundo cáncer más frecuente en las mujeres peruanas. Las limitaciones de los programas nacionales de detección precoz, sobre todo en las regiones rurales, propician que más del 50% de los nuevos casos de cáncer de mama en Perú se diagnostiquen en estadios avanzados. RAD-AID Internacional, en colaboración con una clínica local registrada como organización no gubernamental (CerviCusco), pretende crear una estructura diagnóstica sostenible que mejore el cribado del cáncer de mama en Cuzco. Para ello se ha contado con socios locales, nacionales e internacionales que han colaborado en el análisis de recursos radiológicos, la concienciación de la población, la adquisición de equipamiento, el entrenamiento clínico y las redes de referencia. Nuestros equipos de radiólogos, incluidos en el equipo RAD-AID, han participado en la capacitación ecográfica del personal de CerviCusco, permitiendo una formación adicional a los residentes de radiología gracias a una colaboración internacional reglada.(AU)

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.(AU)

Radiology volunteers to support a breast cancer screening program in Peru: description of the project, preliminary results, and impressions. / Voluntariado radiológico para apoyar un programa de detección precoz del cáncer de mama en Perú: descripción del proyecto, presentación de los primeros resultados e impresiones.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology - Evolution versus revolution.

At a joint workshop organized by RIVM and BfR, international experts from governmental institutes, regulatory agencies, industry, academia and animal welfare organizations discussed and provided recommendations for the development, validation and implementation of innovative 3R approaches in regulatory toxicology. In particular, an evolutionary improvement of our current approach of test method validation in the context of defined approaches or integrated testing strategies was discussed together with a revolutionary approach based on a comprehensive description of the physiological responses of the human body to chemical exposure and the subsequent definition of relevant and predictive in vitro, in chemico or in silico methods. A more comprehensive evaluation of biological relevance, scientific validity and regulatory purpose of new test methods and assessment strategies together with case studies that provide practical experience with new approaches were discussed as essential steps to build up the necessary confidence to facilitate regulatory acceptance.

Mobile Technology Affinity in Renal Transplant Recipients.

BACKGROUND: Medication nonadherence is a common problem in renal transplant recipients (RTRs). Mobile health approaches to improve medication adherence are a current trend, and several medication adherence apps are available. However, it is unknown whether RTRs use these technologies and to what extent. In the present study, the mobile technology affinity of RTRs was analyzed. We hypothesized significant age differences in mobile technology affinity and that mobile technology affinity is associated with better cognitive functioning as well as higher educational level. METHODS: A total of 109 RTRs (63% male) participated in the cross-sectional study, with an overall mean age of 51.8 ± 14.2 years. The study included the Technology Experience Questionnaire (TEQ) for the assessment of mobile technology affinity, a cognitive test battery, and sociodemographic data. RESULTS: Overall, 57.4% of the patients used a smartphone or tablet and almost 45% used apps. The TEQ sum score was 20.9 in a possible range from 6 (no affinity to technology) to 30 (very high affinity). Younger patients had significantly higher scores in mobile technology affinity. The only significant gender difference was found in having fun with using electronic devices: Men enjoyed technology more than women did. Mobile technology affinity was positively associated with cognitive functioning and educational level. CONCLUSIONS: Young adult patients might profit most from mobile health approaches. Furthermore, high educational level and normal cognitive functioning promote mobile technology affinity. This should be kept in mind when designing mobile technology health (mHealth) interventions for RTRs. For beneficial mHealth interventions, further research on potential barriers and desired technologic features is necessary to adapt apps to patients' needs.

Prediction of persistent post-operative pain: Pain-specific psychological variables compared with acute post-operative pain and general psychological variables.

BACKGROUND: Psychological variables and acute post-operative pain are of proven relevance for the prediction of persistent post-operative pain. We aimed at investigating whether pain-specific psychological variables like pain catastrophizing add to the predictive power of acute pain and more general psychological variables like depression. METHODS: In all, 104 young male patients undergoing thoracic surgery for pectus excavatum correction were studied on the pre-operative day (T0) and 1 week (T1) and 3 months (T2) after surgery. They provided self-report ratings (pain-related: Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale = PASS, Pain Vigilance and Awareness Questionnaire = PVAQ; general psychological: Screening for Somatoform Symptoms, State-Anxiety Inventory-X1, Center for Epidemiologic Studies Depression Scale = CES-D). Additional predictors (T1) as well as criterion variables (T2) were pain intensity (Numerical Rating Scale) and pain disability (Pain Disability Index). RESULTS: Three months after surgery, 25% of the patients still reported clinically relevant pain (pain intensity ≥3) and over 50% still reported pain-related disability. Acute post-operative pain as well as general psychological variables did not allow for a significant prediction of persistent post-operative pain; in contrast, pain-related psychological variables did. The best single predictors were PASS for pain intensity and PVAQ for pain disability. CONCLUSIONS: Pain-related psychological variables derived from the fear-avoidance model contributed significantly to the prediction of persistent post-operative pain. The best possible compilation of these measures requires further research. More general psychological variables may become relevant predictors later in the medical history. SIGNIFICANCE: Our results suggest that pain-specific psychological variables such as pain anxiety and pain hypervigilance add significantly to the prediction of persistent post-operative pain and might even outperform established predictors such as acute pain and general psychological variables. Clinicians might benefit from the development of time-economic screening tools based on these variables.

Psychometric Properties of the German Version of the Pain Vigilance and Awareness Questionnaire (PVAQ) in Pain-Free Samples and Samples with Acute and Chronic Pain.

PURPOSE: The way individuals attend to pain is known to have a considerable impact on the experience and chronification of pain. One method to assess the habitual "attention to pain" is the Pain Vigilance and Awareness Questionnaire (PVAQ). With the present study, we aimed to test the psychometric properties of the German version of the PVAQ across pain-free samples and across patients with acute and chronic pain. METHOD: Two samples of pain-free individuals (student sample (N = 255)/non-student sample (N = 362)) and two clinical pain samples (acute pain patients (N = 105)/chronic pain patients (N = 36)) were included in this cross-sectional evaluation of the German PVAQ. Factor structure was assessed using exploratory and confirmatory factor analyses. Reliability was assessed using internal consistency (Cronbach's alpha). Construct validity was tested by assessing correlations between PVAQ and theoretically related constructs. RESULTS: Exploratory factor analysis (non-student sample) and confirmatory factor analysis (student sample, acute pain patient sample) suggested that a two-factor solution best fitted our data ("attention to pain," "attention to changes in pain"). Internal consistency ranged from acceptable to good in all four samples. As hypothesized, the PVAQ correlated significantly with theoretically related constructs in all four samples, suggesting good construct validity in pain-free individuals and in pain patients. CONCLUSION: The German PVAQ shows good psychometric properties across samples of pain-free individuals and patients suffering from pain that are comparable to PVAQ versions of other languages. Thus, the German PVAQ seems to be a measure of pain vigilance equally valid as found in other countries.

[Psychological prophylaxis training for coping with postoperative pain. Long-term effects]. / Psychologisches Prophylaxetraining zur Bewältigung postoperativer Schmerzen. Langfristige Effekte.

INTRODUCTION: The present study was performed to investigate the effect of multidimensional psychological prophylaxis training focusing on coping with cognitive-emotional pain on recovery within the first 12 months after surgery. The training included the following three components: (1) education about pain, analgesia and psychological aspects of coping with pain, (2) training for coping with pain and (3) body-centered relaxation. MATERIAL AND METHODS: In the study 48 young male patients (surgical correction of a chest malformation) were assessed 1 day before surgery, at discharge and 3, 6 and 12 months postoperatively concerning postoperative pain intensity and pain disability as well as pain anxiety, pain catastrophizing and pain hypervigilance. Additionally, 24 of these patients received training on cognitive-emotional coping with pain 1 day before surgery and 1-3 days after surgery (each session 1 h). RESULTS: The proportion of patients with clinically relevant improvement was significantly higher in the training group compared to the control group. This was the case for acute pain intensity (approximately 1 week after surgery), pain disability 3 months later and pain anxiety 12 months after surgery. CONCLUSION: The resurgence of pain anxiety after 12 months could only be found in the control group and could be due to the upcoming surgical removal of the transsternal metal implant. The prophylaxis training can therefore be seen as a protective factor for long-term management of surgery-related consequences and future pain experiences.

Report from the EPAA workshop: in vitro ADME in safety testing used by EPAA industry sectors.

There are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritization, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data.

Effect of the centrifugal force on domain chaos in Rayleigh-Bénard convection.

Experiments and simulations from a variety of sample sizes indicated that the centrifugal force significantly affects the domain-chaos state observed in rotating Rayleigh-Bénard convection-patterns. In a large-aspect-ratio sample, we observed a hybrid state consisting of domain chaos close to the sample center, surrounded by an annulus of nearly stationary nearly radial rolls populated by occasional defects reminiscent of undulation chaos. Although the Coriolis force is responsible for domain chaos, by comparing experiment and simulation we show that the centrifugal force is responsible for the radial rolls. Furthermore, simulations of the Boussinesq equations for smaller aspect ratios neglecting the centrifugal force yielded a domain precession-frequency f approximately epsilon(mu) with mu approximately equal to 1 as predicted by the amplitude-equation model for domain chaos, but contradicted by previous experiment. Additionally the simulations gave a domain size that was larger than in the experiment. When the centrifugal force was included in the simulation, mu and the domain size were consistent with experiment.

Characterization of the domain chaos convection state by the largest Lyapunov exponent.

Using numerical integrations of the Boussinesq equations in rotating cylindrical domains with realistic boundary conditions, we have computed the value of the largest Lyapunov exponent lambda1 for a variety of aspect ratios and driving strengths. We study in particular the domain chaos state, which bifurcates supercritically from the conducting fluid state and involves extended propagating fronts as well as point defects. We compare our results with those from Egolf, [Nature 404, 733 (2000)], who suggested that the value of lambda1 for the spiral defect chaos state of a convecting fluid was determined primarily by bursts of instability arising from short-lived, spatially localized dislocation nucleation events. We also show that the quantity lambda1 is not intensive for aspect ratios Gamma over the range 20

Lyapunov exponents for small aspect ratio Rayleigh-Bénard convection.

Leading order Lyapunov exponents and their corresponding eigenvectors have been computed numerically for small aspect ratio, three-dimensional Rayleigh-Benard convection cells with no-slip boundary conditions. The parameters are the same as those used by Ahlers and Behringer [Phys. Rev. Lett. 40, 712 (1978)] and Gollub and Benson [J. Fluid Mech. 100, 449 (1980)] in their work on a periodic time dependence in Rayleigh-Benard convection cells. Our work confirms that the dynamics in these cells truly are chaotic as defined by a positive Lyapunov exponent. The time evolution of the leading order Lyapunov eigenvector in the chaotic regime will also be discussed. In addition we study the contributions to the leading order Lyapunov exponent for both time periodic and aperiodic states and find that while repeated dynamical events such as dislocation creation/annihilation and roll compression do contribute to the short time Lyapunov exponent dynamics, they do not contribute to the long time Lyapunov exponent. We find instead that nonrepeated events provide the most significant contribution to the long time leading order Lyapunov exponent.

Scaling laws for rotating Rayleigh-Bénard convection.

Numerical simulations of large aspect ratio, three-dimensional rotating Rayleigh-Bénard convection for no-slip boundary conditions have been performed in both cylinders and periodic boxes. We have focused near the threshold for the supercritical bifurcation from the conducting state to a convecting state exhibiting domain chaos. A detailed analysis of these simulations has been carried out and is compared with experimental results, as well as predictions from multiple scale perturbation theory. We find that the time scaling law agrees with the theoretical prediction, which is in contradiction to experimental results. We also have looked at the scaling of defect lengths and defect glide velocities. We find a separation of scales in defect diameters perpendicular and parallel to the rolls as expected, but the scaling laws for the two different lengths are in contradiction to theory. The defect velocity scaling law agrees with our theoretical prediction from multiple scale perturbation theory.

Traveling waves in rotating Rayleigh-Bénard convection: analysis of modes and mean flow.

Numerical simulations of the Boussinesq equations with rotation for realistic no-slip boundary conditions and a finite annular domain are presented. These simulations reproduce traveling waves observed experimentally. Traveling waves are studied near threshold by using the complex Ginzburg-Landau equation (CGLE): a mode analysis enables the CGLE coefficients to be determined. The CGLE coefficients are compared with previous experimental and theoretical results. Mean flows are also computed and found to be more significant as the Prandtl number decreases (from sigma=6.4 to sigma=1). In addition, the mean flow around the outer radius of the annulus appears to be correlated with the mean flow around the inner radius.

Genomic structure of the human Ah receptor nuclear translocator gene (hARNT).

The vertebrate basic helix-loop-helix/Per-ARNT-Sim (bHLH/PAS protein) ARNT (aryl hydrocarbon receptor nuclear translocator) plays a crucial role in transcriptional regulation as the common subunit of a number of transcriptionally active complexes. Several studies indicate that ARNT might be involved in the pathogenesis of various genetic diseases. In this study we provide the first report on the genomic structure of the human ARNT gene (hARNT). Human BAC and PAC libraries were screened, and clones positive for ARNT were mapped, subcloned, and sequenced. The gene has an overall size of about 65 kb and consists of 22 exons varying in size from 25 to 214 bp. Splice junctions follow the GT/AG consensus except for intron 11 starting with GC at its 5' end. Knowledge of exon-intron boundaries and intronic sequences neighboring the exons allows the extended search for polymorphisms and variants in human genomic DNA. The exonintron arrangement is highly similar to the murine arnt gene (marnt) except for a slight shift in the last three exons. 5' RACE indicated several transcription start sites, one of them identical with the major transcription start site of marnt.

Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes.

New proteins and modules have been invented throughout evolution. Gene "birth dates" in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are "metazoan" genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin.

Chromosome topology and genome size of selected actinomycetes species.

Information about the genome organization of actinomycetes species is restricted to a few genera: Corynebacterium, Mycobacterium, Rhodococcus, Saccharopolyspora and Streptomyces. Streptomyces species and Saccharopolyspora erythraea were shown to contain a single linear 8 Mb chromosome. In contrast, the Corynebacterium, Mycobacterium and Rhodococcus species studied were demonstrated to possess a smaller (3 Mb-6.5 Mb) single circular chromosome. To investigate whether linear chromosome topology and genome sizes above 7 Mb are unique features of Streptomyces and S. erythraea we have started to investigate the chromosome topology, the genome size and the status of accessory elements of additional actinomycetes species: Actinoplanes philippinensis, Amycolatopsis orientalis, Micromonospora chalcea, Nocardia asteroides, Rhodococcus opacus and Streptoverticillium abikoense. Our data which are based on PFGE experiments clearly suggest that large genome sizes and chromosome linearity are seen in mycelium forming actinomycetes genera. In addition we have identified large linear plasmids in Nocardia asteroides, Streptoverticillium abikoense and Rhodococcus opacus.

Purification and analysis of authentic CLIP-170 and recombinant fragments.

We have purified authentic CLIP-170 (cytoplasmic linker protein of 170 kDa) and fragments comprising functional domains of the protein to characterize the structural basis of the function of CLIP-170. Analysis of authentic CLIP-170 and the recombinant fragments by electron microscopy after glycerol spraying/low angle rotary metal shadowing reveals CLIP-170 as a thin, 135-nm-long molecule with two kinks in its central rod domain, which are approximately equally spaced from the two ends of the protein. The central domain consisting of heptad repeats, which is alpha-helical in nature and forms a 2-stranded coiled-coil, mediates dimerization of CLIP-170. The rod domain harbors two kinks, each spaced approximately 37 nm from the corresponding end of the molecule, thus providing mechanical flexibility to the highly elongated molecule. The N-terminal domain of CLIP-170 binds to microtubules in vitro with a stoichiometry of one dimeric head domain per four tubulin heterodimers. Authentic CLIP-170 binds to microtubules with lower stoichiometry, indicating that the rod and tail domains affect microtubule binding of CLIP-170. These results document that CLIP-170 is a highly elongated polar molecule with the microtubule-binding domain and the organelle-interacting domains at opposite ends of the homodimer, thus providing a structural basis for the function of CLIP-170 as a microtubule-organelle linker protein.

Adeno-retroviral chimeric viruses as in vivo transducing agents.

Several hybrid viral gene transfer systems have been described that exploit the favorable features of the two parent viral species. We have developed a hybrid adeno-retroviral vector system to generate a retroviral vector in situ. The system consists of adenoviruses encoding MoMLV gag.pol (Axtet.gag.pol), the VSV-G viral envelope (Axtet.VSV-G), the retroviral vector LXSN expressing the neomycin phosphotransferase gene (AV-LXSN) and a transcriptional regulator to control expression of gag.pol and envelope (AV-rtTA). In vitro, biologically active retroviral vector preparations were generated following adeno-retroviral transduction of 9L rat glioma cells. In vivo the transcomplementing adeno-retroviruses were co-administered intratumorally into subcutaneous 9L glioma tumors in rats and human A375 melanoma xenografts in nude mice. In the 9L rat model, G418 cell cultures were only obtained when 9L cells were harvested from tumors injected with all four transcomplementing adeno-retroviruses. Molecular analysis of DNA extracted from 9L G418 populations derived both in vitro and in vivo showed appropriate integration of the LXSN proviral sequence. Tumor cells were harvested 1, 3 and 4 weeks after adeno-retrovirus administration to the human A375 xenografts. The percentage of G418 colonies recovered from tumors transduced with all of the transcomplementing adeno-retroviruses increased with time, whereas no increase was observed in tumors transduced with AV-LXSN alone. DNA extracted from G418 A375 cell populations showed the presence of integrated proviral sequences only in animals that received the full complement of adeno-retroviruses. These results demonstrate that adenoviral vectors expressing transcomplementing genes for retroviral proteins and retroviral vector RNAs can be used for in situ transduction of target cells.