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This study employs qualitative methodology to assess surgeons' perspective on decision making in management of recurrent diverticulitis to improve patient-centered decision making.The decision to pursue colectomy for patients with recurrent diverticulitis is nuanced. Strategies to enact broad acceptance of guidelines for surgery are hindered because of a knowledge gap in understanding surgeons' current attitudes and opinions.We performed semi-structured interviews with board-certified North American general and colorectal surgeons who manage recurrent diverticulitis. We purposely sampled specialists by both surgeon and practice factors. An iterative inductive/deductive strategy was used to code and analyze the interviews and create a conceptual framework.25 surgeons were enrolled over a nine-month period. There was diversity in surgeons' gender, age, experience, training, specialty (colorectal vs general surgery) and geography. Surgeons described the difficult process to determine who receives an operation. We identified seven major themes as well as twenty subthemes of the decision-making process. These were organized into a conceptual model. Across the spectrum of interviews, it was notable that there was a move over time from decisions based on counting episodes of diverticulitis to a focus on improving quality of life. Surgeons also felt that quality of life was more dependent on psychosocial factors than the degree of physiological dysfunction. [What about what surprised you/].Surgeons mostly have discarded older dogma in recommending colectomy for recurrent diverticulitis based on number and severity of episodes. Instead, decision making in recurrent diverticulitis is complex, involving multiple surgeon and patient factors and evolving over time. Surgeons struggle with this decision and education- or communication-based interventions that focus on shared decision making warrant development.

Telehealth is the use of electronic information and technology for long-distance clinical care. In direct-to-patient (DTP) telehealth, the patient initiates care from a personal computer or mobile device to a medical provider. While information on standard clinic-to-clinic telehealth exists, less is known about DTP telehealth in pediatric populations. Using quantitative and qualitative data, we examined DTP telehealth for low-income pediatric patient-families and compared the experience of English and non-English speakers.Telehealth visits for acute and preventive care took place from April 2020 to May 2020 at a pediatric primary care clinic (80% Medicaid-insured, 40% non-English-speaking). Patients and primary care providers conducted the visit through the clinic's portal or other platforms (WhatsApp, FaceTime, Zoom). Providers completed an electronic survey with patient feedback about the telehealth experience and their own observations. An iterative inductive/deductive approach informed a coding scheme for free-text survey responses consisting of five domains.REDCap surveys were completed for 258 (52%) of telehealth visits. There was an overrepresentation of English visits compared to the overall clinic population and the majority of visits were via mobile phone. Visits with English speakers utilized the patient portal and had positive process ease ratings more often than those with non-English speakers. Providers rated most telehealth visits as satisfactory, with contributing elements including family call environment, technology process and experience, value added, and barriers.Expanding telehealth in pediatrics without worsening health disparities requires building digital health that is user-friendly on mobile technology, facilitating patient preferred language, and simplifying logistical processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Tissue specimens are valuable materials for microbiological diagnosis. The method of tissue processing can have a significant effect on sensitivity. This study aimed to compare different biopsy processing methods in terms of efficacy and standardization. Pork tissue artificially inoculated with Staphylococcus aureus and Escherichia coli, and samples of infected human tissue were processed by different methods before culture, and the results compared. Bacterial recovery from artificially inoculated pork tissue was significantly higher by homogenization with GentleMacs Dissociator than with sonication. No significant difference was observed between the GentleMacs Dissociator and manual treatment with a scalpel and vortexing. The microbial yield from homogenized human tissues was significantly higher after homogenization with GentleMacs Dissociator than with the conventional method. Homogenization with the GentleMacs Dissociator retrieves bacteria from tissue effectively. Tissue homogenization with the Dissociator is easy and fast to perform and allows for a high degree of standardization.

Purpose: Lung cancer is the leading cause of cancer death in the U.S. Lung cancer screening significantly reduces lung cancer mortality, but national uptake is low ( Citation Format: Jennifer Richmond, Jessica R. Fernandez, Kemberlee R. Bonnet, Maria A. Pena, Allana T. Forde, David G. Schlundt, Consuelo H. Wilkins, Melinda C. Aldrich. Evaluating medical mistrust in efforts to promote equity in lung cancer screening implementation [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A116.

Recovery of severely deformed ferrite was followed in situ by High Energy X Ray Diffraction during heating and isothermal holding experiments. Dislocation densities during annealing were determined by a modified Williamson Hall method. The deduced recovery kinetics was compared to post-mortem hardness measurements. A temperature dependent saturation of recovery was exhibited during holding. Dislocation density drop and saturation behavior cannot be reproduced simultaneously by the classical physically based models.

International audience; Knowledge of phase transformation kinetics is a key point in designing steel grades, in particular modern high-performance grades, highly sought-after in energy and transportation applications. The design space for these grades is highly multi-dimensional given the numerous potential alloying elements. The characterization techniques that are usually relied on to assess transformation kinetics, such as metallography or dilatometry, are highly time consuming, due to their limitation to either a single transformation time or a single composition per experiment. The high-throughput approach showcased here overcomes those limitations by combining compositionally graded samples with time-and space-resolved in situ Xray diffraction, yielding full kinetic records over a range of compositions in a single run. Its application to low-alloy steel required addressing specific challenges related to the reactivity and thermodynamics of the material. The transformation of austenite into ferrite was chosen to illustrate its benefits. Using the rich resulting database, the transformation mechanism was examined quasi-continuously across sections of the composition space. Neither the paraequilibrium, nor the local equilibrium with negligible partitioning model, nor a transition from the former to the latter is applicable over the whole range of investigated conditions. Instead, the observed kinetics were explained by accounting for the solute drag exerted on the mobile interface. This work is a major contribution in accelerating the design of future low-alloy steel grades, involving the transformation of austenite into ferrite or any other transformation to which the present high-throughput methodology can be adapted.

Acta materialia 212, 116920 (2021). doi:10.1016/j.actamat.2021.116920, The manufacturing of Dual-Phase steels includes as a crucial step the annealing of a cold-rolled ferrite-pearlite (F/P) microstructure, which involves numerous and interacting metallurgical mechanisms, namely recovery/recrystallization of ferrite, globularization, manganese enrichment, coarsening of cementite and finally austenite transformation. Present study focuses on the austenite transformation considering its interaction with the ferrite recrystallization and the influence of the chemical composition of the cementite. The behavior of a cold-rolled F/P microstructure is studied at three heating rates to induce weak and strong interactions between the mechanisms, in particular using post mortem microstructure observations but also in situ High Energy X-Ray Diffraction experiments on a synchrotron beamline. Slow heating leads to a necklace austenite distribution whereas fast heating conducts to a banded topology. This particular microstructure morphogenesis is explained by the presence of numerous intergranular (or isolated) carbides inside the ferrite matrix, inherited from the hot-rolling. Thermokinetic analysis accounting for the cementite composition shows that the pearlite islands transformation necessarily involves the partition of substitutional elements. Conversely, the dissolving isolated carbides undergo a partition/partitionless transition on heating. After the dissolution of the cementite, a final ferrite/austenite transformation takes place. The phase transformation kinetics increases with increasing heating rates, despite the thermal-activated nature of the austenite growth process. This is interpreted thanks to kinetic simulations with DICTRA software, which allow to analyze the austenite growth regimes involving or not the partition of the alloying elements., Published by Elsevier Science, Amsterdam [u.a.]

International audience; The aim of this paper is to investigate the effective properties of Fe–TiB2 composites obtained after hot or cold rolling. The elastic moduli of both hot and cold rolled composites are measured experimentally using several methods. Microstructure analyses based on SEM observations are performed to characterize the distribution of particles and cracks, and are then used to generate 3D representative microstructures using the RSA method. This allows the numerical determination of the overall elastic behavior of Fe–TiB2 composites using full-field FFT-based simulations. In addition, Young’s moduli of the hot rolled Fe–TiB2 composites are also determined analytically using the mean-field homogenization scheme of Mori–Tanaka. The elastic properties determined experimentally, analytically and numerically are in a good agreement. Overall, a significant improvement of the specific stiffness in comparison to standard steels is achieved irrespective of the processing conditions

The evolution of the dislocation densities in martensite and in austenite during the quench of a low-carbon (0.215 wt% C) steel is investigated in situ by the mean of a High Energy X-Ray Diffraction experiment on a synchrotron beamline. The line configuration offers an excellent time resolution well adapted to the studied martensitic transformation kinetics. The mean density of dislocations in martensite increases as the transformation proceeds confirming that dislocations are not homogeneously distributed between the laths in agreement with some recent post-mortem observations. The resulting spatial distribution of dislocations and the associated strain-hardening support the views assuming that lath martensite is a heterogeneous microstructure and behaves as a “multiphase” aggregate. In austenite, the increase in dislocation densities is even more significant meaning that austenite in martensite is also a hard phase, contradicting some recent theories attributing to films of retained austenite a major role in the plasticity of martensite.

International audience; An original mean field model for the nucleation and the growth of new recrystallized grains during annealing treatments of deformed, low-carbon ferritic steels is proposed in this paper. The model was calibrated on two steels extensively studied in the literature under both isothermal annealing and continuous heating schedules. It permits one to predict not only recrystallization kinetics but also advanced microstructural features (such as dislocation density, dislocation cell size and grain size) during complex heat treatments. Once calibrated, the model was applied to the case of a third ferrite/pearlite steel and was shown to accurately capture the effect of cold-rolling ratio on the recrystallization kinetics.

The growth kinetics of ferrite during intercritical annealing of steel has been investigated using in situ high energy X-ray diffraction with a specially designed furnace allowing highly quantitative measurements of phase volume fractions. Kinetics have been obtained at 730 ∘ C, 750 ∘ C and 775 ∘ C in different ternary Fe-C-X (where X : Mn, Ni, Mo and Cr) alloys and in a quaternary Fe-C-1Mn-1Cr (wt.%) alloy. The obtained results were compared with the predictions of classical Local Equilibrium and Para-Equilibrium models as well as an improved version of a three-jump solute drag model, where the interactions between the solute elements and the moving interface are described comprehensively. Good agreement was obtained between the measured ferrite growth kinetics and the predictions of the solute drag model for the different Fe-C-X systems using only one fitting parameter, namely the Fe-X interaction parameter at the interface. The interactions found here qualitatively match those reported in literature for all solutes except for Ni, which displayed an attractive interaction with the interface. For the quaternary Fe-C-Mn-Cr system, the solute drag model succeeded in predicting ferrite growth kinetics using the same interaction values as used for the ternary Fe-C-Mn and Fe-C-Cr systems.

Objectives The aim was to assess the incidence of sink contamination by multidrug-resistant (MDR) Pseudomonas aeruginosa and Enterobacteriaceae, risk factors for sink contamination and splashing, and their association with clinical infections in the intensive care setting. Methods A prospective French multicentre study (1 January to 30 May 2020) including in each intensive care unit (ICU) a point-prevalence study of sink contamination, a questionnaire of risk factors for sink contamination (sink use, disinfection procedure) and splashing (visible plashes, distance and barrier between sink and bed), and a 3-month prospective infection survey. Results Seventy-three ICUs participated in the study. In total, 50.9% (606/1191) of the sinks were contaminated by MDR bacteria: 41.0% (110/268) of the sinks used only for handwashing, 55.3% (510/923) of those used for waste disposal, 23.0% (62/269) of sinks daily bleached, 59.1% (126/213) of those daily exposed to quaternary ammonium compounds (QACs) and 62.0% (285/460) of those untreated; 459 sinks (38.5%) showed visible splashes and 30.5% (363/1191) were close to the bed ( Discussion Our data showed frequent and multifactorial infectious risks associated with contaminated sinks in ICUs.

International audience; The thermo-mechanical properties of a ferritic-steel-based metal matrix composite reinforced with titanium diboride (TiB 2) particles were studied using synchrotron X-ray diffraction. The samples were subjected to in situ heat treatment to investigate the effect of the mismatch in the coefficient of thermal expansion between the matrix and reinforcement. In addition, in situ tensile tests were performed to examine the load partitioning in the composite. Load transfer from the ferritic matrix to the TiB 2 particles was observed at the onset of plasticity in the matrix.

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/mu l compared with 500 cells/mu l and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Metals 9(1), 8 - (2019). doi:10.3390/met9010008, The annealing process of cold-rolled ferrite/pearlite steel involves numerous metallurgicalmechanisms as recovery/recrystallization of deformed phases, ripening of carbide microstructure,and austenite transformation in the intercritical domain. The interactions between these mechanismsgovern the morphogenesis of the transformed austenite microstructure and, thus, the final propertiesof the steel. This paper demonstrates that high energy X-ray diffraction (HEXRD) on synchrotronbeamline offers the unique possibility to follow concomitantly these mechanisms in situ duringa single experiment. A cold-rolled ferrite-pearlite steel dedicated to the industrial production ofDual-Phase steel serves as case-study. Synchrotron experiments have been conducted in transmissionat 100 keV with a 2D detector. Diffraction patterns acquired all along an annealing treatment are firstanalyzed after circular integration. A Rietveld refinement procedure coupled with a Williamson-Hallapproach is used to determine phase transformation and recovery kinetics. In this paper, a newmethod inspired by the 3D X-ray diffraction tomography is proposed to follow recrystallizationkinetics at the same time. It is based on a systematic detection of individual diffraction spots relatedto newly recrystallized grains appearing on Debye-Scherrer rings. The deduced recrystallizationkinetics is compared and validated by more conventional ex situ methods., Published by MDPI, Basel

In-situ high energy X-Ray diffraction (HEXRD) was used on compositionally graded steels to study the effect of substitutional elements on ferrite growth kinetics in Fe&ndash, C&ndash, X and Fe&ndash, X&ndash, Y systems. Two systems were selected to illustrate the applicability of the combinatorial approach in studying such transformations, Fe&ndash, Mn and Fe&ndash, Mn&ndash, Mo. Comparison between the measured ferrite growth kinetics using HEXRD and the predicted ones using Para-Equilibrium (PE) and Local Equilibrium with Negligible Partitioning (LENP) models indicates that the fractions reached at the stasis of transformation are lower than the predicted ones. Experiments indicated a deviation of measured kinetics from both PE and LENP models when increasing Mn and decreasing Mo (in Fe&ndash, Mo system). The large amount of data that can be obtained using this approach can be used for validating existing models describing ferrite growth kinetics.

International audience; ObjectivesWe previously described extended-spectrum oxacillinase OXA-145 from Pseudomonas aeruginosa, which differs from narrow-spectrum OXA-35 by loss of Leu-155. The deletion results in loss of benzylpenicillin hydrolysis and acquisition of activity against ceftazidime. We report the crystal structure of OXA-145 and provide the basis of its switch in substrate specificity.MethodsOXA-145 variants were generated by site-directed mutagenesis and purified to homogeneity. The crystal structure of OXA-145 was determined and molecular dynamics simulations were performed. Kinetic parameters were investigated in the absence and in the presence of sodium hydrogen carbonate (NaHCO3) for representative substrates.ResultsThe structure of OXA-145 was obtained at a resolution of 2.3 Å and its superposition with that of OXA-10 showed that Trp-154 was shifted by 1.8 Å away from the catalytic Lys-70, which was not N-carboxylated. Addition of NaHCO3 significantly increased the catalytic efficiency against penicillins, but not against ceftazidime. The active-site cavity of OXA-145 was larger than that of OXA-10, which may favour the accommodation of large molecules such as ceftazidime. Molecular dynamics simulations of OXA-145 in complex with ceftazidime revealed two highly coordinated water molecules on the α- or β-face of the acyl ester bond, between Ser-67 and ceftazidime, which could be involved in the catalytic process.ConclusionsDeletion of Leu-155 resulted in inefficient positioning of Trp-154, leading to a non-carboxylated Lys-70 and thus to loss of hydrolysis of the penicillins. Ceftazidime hydrolysis could be attributed to enlargement of the active site and to a catalytic mechanism independent of the carboxylated Lys-70.

Steel-based composites reinforced with titanium diborides (TiB 2 ) and produced by eutectic solidification display a significant increase in specific stiffness ( E / ρ ) in comparison with usual steels. A significant lightening can be achieved in parts designed for stiffness with a high Young’s modulus and a low density. They can be produced through the use of industrial continuous casting devices and can be hot rolled without any damage. This production route guarantees a good cohesion of the steel/reinforcement interface and the control of the main parameters that determine the final properties of the product (size, shape, clustering of reinforcements). In order to get a better understanding of the composite properties, its microstructural features after hot rolling are investigated through transmission electron microscopy at microscopic and atomic levels. TiB 2 reinforcements are homogeneously distributed in the ferritic iron matrix. Interfaces between Fe and TiB 2 particles are mainly parallel to dense planes of the diboride, with a preferential growth of prismatic planes { 1 0 1 ¯ 0 } . Interfacial misfit dislocations occur at interfaces parallel to the prismatic planes. The TiB 2 basal plane is covered by a TiC layer three atomic planes in width. The hot rolling operation induces a significant plastic deformation in the TiB 2 particles, with the activation of basal and prism plane slip systems. All these characteristics may account for the good behaviour of the composite in terms of hot rolling capability.

Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per mu L, 350 cells per mu L, and 500 cells per mu L. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4.0 months and viral load every 3.8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1.05 (95% CI 0.86-1.29) for threshold 200 and 1.02 (0.91.1.14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95-1.22) for threshold 200 and 1.03 (0.96-1.12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2.01 (1.17-3.43) for threshold 200 and 1.24 (0.89-1.73) for threshold 350, and 24 month mean CD4 cell count differences were 0.4 (-25.5 to 26.3) cells per mu L for threshold 200 and -3.5 (-16.0 to 8.9) cells per mu L for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per mu L compared with higher than 500 cells per mu L does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies.

Neuroendokrine Neoplasien der Lunge leiten sich von diffus im Korper verteilten enterochromaffinen Zellen her. Die Inzidenz der neuroendokrinen Neoplasien der Lunge ist in den letzten Jahrzehnten aufgrund der zur Verfugung stehenden Diagnostik deutlich angestiegen, sie machen etwa 1 – 2 % aller Lungentumoren und ca. 20 – 30 % aller neuroendokrinen Neoplasien aus. Die aktuelle WHO-Klassifikation ist aus dem Jahre 2004 und unterteilt typische Karzinoide (TC), atypische Karzinoide (AC), groszellige Lungenkarzinome (LCNEC) und kleinzellige Lungenkarzinome (SCLC). Die wichtigsten neuroendokrinen Biomarker sind Chromogranin A, CD56 und Synaptophysin. TC haben eine geringe Mitoserate von Die steigende Zahl der therapeutischen Moglichkeiten und diagnostische Verfahren erfordert ein multidisziplinares Vorgehen und eine Entscheidungsfindung in multidisziplinaren Tumorkonferenzen, um eine „masgeschneiderte“ Therapie zu gewahrleisten, weshalb Patienten mit einer neuroendokrinen Neoplasie der Lunge in spezialisierten Zentren behandelt werden sollten.

Bei der hereditaren hamorrhagischen Teleangiektasie (HHT, Morbus Osler-Weber-Rendu) kann es zur Ausbildung von pulmonalen arteriovenosen Malformationen (pAVM) kommen. Zur Vermeidung von Komplikationen und zum Verschluss relevanter AV-Shunts sollte eine Embolisation der Malformationen vorgenommen werden. Im vorliegenden Fallbeispiel kam es zum Abhusten von Embolisationsspiralen 15 Jahre nach Intervention. Bei Hamoptysen nach Interventionen mit Embolisationsspiralen sollte auch Jahre nach deren Implantation neben dem Verdacht auf neue AV-Malformationen an durchwanderte Spiralen gedacht und eine entsprechende Diagnostik durch Einsatz von Thorax-CT mit Kontrastmittel und Bronchoskopie durchgefuhrt werden.

Anlasslich des 50. Geburtstags der Wissenschaftlichen Arbeitsgemeinschaft fur die Therapie von Lungenkrankheiten (WATL) wird ihre Geschichte von der Grundung bis zur heutigen Situation dargestellt. Es werden die Forschungsthemen der WATL uber diese lange Zeit hinweg benannt und wesentliche Studien der WATL kurz charakterisiert. Fruh vor allem mit Studien zur Tuberkulose beschaftigt, hat sich das Spektrum der WATL dann erheblich verbreitert und Krankheiten wie die Sarkoidose, die pulmonale Langerhans-Zell-Histiozytose, das Lungenemphysem beim α1-Antitrypsin-Mangel, die chronisch-obstruktive Bronchitis und das Asthma bronchiale sowie die nichttuberkulosen Mykobakteriosen ins Visier genommen. Schlieslich in der Erkenntnis, dass die methodischen Moglichkeiten fur grose Studien bei den klassischen Lungenkrankheiten unter aktuellen Anforderungen nicht ausreichen, hat die WATL begonnen, sich eine Kompetenz auf dem Sektor der seltenen Lungenkrankheiten wie Lymphangioleiomyomatose und Alveolarproteinose zu erwerben. Zusatzlich hat sich die WATL mit ihren nun zum dritten Mal durchgefuhrten Kongressen in Berlin ein edukatives Ziel im Bereich der nicht zum Mainstream gehorenden Fragen in der Pneumologie auf die Fahnen geschrieben.

Introduction: CT alone cannot provide sufficient information referring to response after neoadjuvant therapy in a timely manner. To evaluate the role of 18F-FDG-PET after neoadjuvant chemoradiation as a valid, non-invasive predictor for early therapy response and its effect on survival as compared to histopathologic tumor response, data of 32 of 210 randomized patients with NSCLC stage IIIA/IIIB, who were treated in a prospective randomized controlled multicenter trial (LUCAS- MD), were re-evaluated. Material and Methods: For 32 patients with NSCLC stage IIIA (44%) IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m2 paclitaxel and carboplatin AUC 6 d1q22) and concomitant chemoradiation (50 mg/m2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5 Gy b.i.d. up to 45 Gy). Documentation of involved lymph node stations as detected by 18F-FDG-PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al. (2001) and correlation with 18F-FDG-PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates and log rank tests. Results: Actuarial tumor specific survival for the 32 patients with concomitant chemoradiation plus chemotherapy: complete vs. incomplete metabolic remission prior to surgery after 60 months: 40% vs. 24% (p = 0.018). RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs. 15% (p = 0.006). 18/32 (56%) patients had RG III/IIb, 8/32 (25%) patients had regression grade III. 1/8 pts. with RG III were in the 18F-FDG- PET/CT false positive, 10 pts. with RG IIb (i.e. all pts. with RG IIb) were in the 18F-FDG-PET/CT false negative. One patient with RG IIa was in the 18F-FDG-PET/CT false negative. Hence, the cut-off level in detecting vital tumor cells by 18F-FDG-PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Conclusion: Histological regression grading correlates well with metabolic remission as detected by 18F-FDG-PET. Thus, 18F-FDG-PET precedes CT in measuring the tumor response and may predict long-term therapeutic outcome in patients with stage III NSCLC. Invasive staging procedures may be avoided and patients who will not profit from resection due to insufficient downstaging after neoadjuvant treatment will be easily detected by using 18F-FDG-PET as standard imaging in workup and evaluation of treatment response.

Cementite composition in a ferrite-pearlite steel dedicated to the industrial production of Dual-Phase steels has been investigated after hot-rolling and during annealing. By coupling TEM investigations and local field composition modeling using THERMOCALC and DICTRA softwares, its progressive enrichment in manganese is explained. This enrichment begins during hot-rolling when austenite first decomposes into ferrite and pearlite. Measured enrichments are consistent with a pearlite transformation process governed by two simultaneous local equilibria at the growing fronts between ferrite, cementite and austenite. During subsequent coiling operation and annealing, cementite enrichment in manganese continues. Observed composition profiles can be reproduced considering diffusion simulations with local equilibrium at ferrite/cementite interface. Nevertheless, the known diffusion coefficient of manganese in cementite has been reassessed to explain observed composition gradients. Both thermodynamic approach of pearlite phase transformation and diffusion simulation must be coupled to follow seamlessly manganese composition gradients in cementite all along the manufacturing process. Such calculation is the key to understand the inheritance effects of hot-rolling on final properties on Dual-Phase steels.

We discuss the performances of (001) and (110) oriented gate-all-around silicon nanowire (Si NW) transistors within a nonequilibrium Green's functions framework, taking surface roughness and phonon scatterings into account. We show, in agreement with previous studies, that uniaxial tensile (respectively, compressive) strains can significantly improve the mobility of electrons (respectively, holes) in the channel. This does not, however, necessarily result in a comparable enhancement of the device performances. Indeed, the current in short channels is limited by both the scattering and the number of sub-bands available for carrier transport in quantum confined systems (intrinsic “ballistic” resistance). The dependence of the mobility and ballistic resistance on strains can be different, which calls for a careful design of the devices. We show, in this respect, that (110) Si NWs provide the best opportunities for strain engineering in ultimate short channel transistors.

Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 +/- 1 months, (2) 6 +/- 1 months, and (3) 9-12 +/- 1 months. We used inverseprobability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -25.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Fragment-based design was used to guide derivatization of a lead series of β-lactamase inhibitors that had heretofore resisted optimization for in vivo activity. X-ray structures of fragments overlaid with the lead suggested new, unanticipated functionality and points of attachment. Synthesis of three derivatives improved affinity over 20-fold and improved efficacy in cell culture. Crystal structures were consistent with the fragment-based design, enabling further optimization to a K i of 50 pM, a 500-fold improvement that required the synthesis of only six derivatives. One of these, compound 5 , was tested in mice. Whereas cefotaxime alone failed to cure mice infected with β-lactamase-expressing Escherichia coli , 65% were cleared of infection when treated with a cefotaxime: 5 combination. Fragment complexes offer a path around design hurdles, even for advanced molecules; the series described here may provide leads to overcome β-lactamase-based resistance, a key clinical challenge.

Hintergrund: Neuroendokrine Tumore der Lunge weisen eine deutlich ansteigende Inzidenz auf. Uber Diagnose und Therapie dieser Tumoren existieren jedoch nur wenig gesicherte Informationen. Demgegenuber liegen deutlich mehr Daten fur die neuroendokrinen Tumore des gastroenteropankreatischen Systems vor. Methode: Dialog mit Fachexperten fur neuroendokrine Tumore (NET) des gastroenteropankreatischen Systems und der Lunge am 25. und 26. Februar 2011 in Weimar, um Gemeinsamkeiten und Unterschiede zwischen den neuroendokrinen Tumoren der Lunge und des gastroenteropankreatischen Systems herauszustellen. Ergebnisse: Die neuroendokrinen Tumoren der Lunge weisen viele Gemeinsamkeiten, aber auch einige Unterschiede mit den gastroenteropankreatischen NETgastroenteropankreatischen Tumoren auf. Gemeinsamkeiten bestehen vor allem in der Pathologie, der Diagnosestellung und der Therapie. Unterschiede bestehen in den Empfehlungen zur systemischen Therapie und der deutlich geringeren Inzidenz paraneoplastischer Syndrome. Das Somatostatinrezeptor-PET/CT mit Gallium-68 konjugierten Somatostatinanaloga und die Peptid-Rezeptor vermittelte Radiorezeptortherapie sind innovative Verfahren fur die neuroendokrinen Tumore der Lunge. An erster Stelle der Therapie steht jedoch die komplette kurative Resektion. Erste Ergebnisse von Studien mit molekularen Wirkstoffen wie Everolimus (Afinitor®) zeigen eine Wirksamkeit an. Schlussfolgerungen: Es existieren deutliche Schnittmengen in der Diagnose und Therapie der neuroendokrinen Tumore der Lunge und des gastroenteropankreatischen Systems. Weitere Studien sind geplant und notwendig, um die Datenlage zu verbessern. Ein Register zur Erfassung der neuroendokrinen Tumore der Lunge ware sinnvoll.

It is commonly known in economics that markets follow both positive and/or negative trends, crashes and bubble effects. In general a strong positive trend is followed by a crash. Famous examples of these effects were seen in the recent crash on the NASDAQ (April 2000) and prior to the crash on the Hong Kong market, which was associated with the Asian crisis in the early 1994. In this paper we use real market data input into a minority game with a variable payoff function and a nonlinear super exponential model for bubbles, to explore financial bubbles. By changing the payoff function in the minority game we study how one can get the price function to follow the dynamics of a real market.

We describe the characterization of a novel CTX-M β-lactamase from Salmonella enterica . Four S. enterica isolates (three of serotype Westhampton and one of serotype Senftenberg) resistant to extended-spectrum cephalosporins (cefotaxime and ceftazidime) were recovered in 2004 from living cockles in three supermarkets located in distant geographic areas in France, which got their supplies from the same fishery. The isolates were found to produce a novel extended-spectrum β-lactamase (ESBL) belonging to the CTX-M-1 phylogenetic group and named CTX-M-53. The CTX-M-53 β-lactamase harbored the substitution Asp240Gly, like the CTX-M-15 enzyme, which is specifically implicated in a higher catalytic efficiency against ceftazidime. The bla CTX-M-53 gene was located on a mobilizable 11-kb plasmid, pWES-1. The complete sequence of pWES-1 revealed the presence of a novel insertion sequence, IS Sen2 , and an IS 26 element upstream and downstream of the bla CTX-M-53 gene, respectively; however, transposition assays of the bla CTX-M-53 gene were unsuccessful. IS 26 elements may have contributed to the acquisition of the bla CTX-M-53 gene. Interestingly, the mobilization module of the pWES-1 plasmid was similar to that of quinolone resistance plasmids (carrying the qnrS2 gene) from aquatic sources. Although belonging to two serotypes differentiated on the basis of the O-antigen structure (E1 or E4 groups), the isolates were found to be genetically indistinguishable by pulsed-field gel electrophoresis. Multilocus sequence typing showed that the isolates of serotype Westhampton had a sequence type, ST14, common among isolates of serotype Senftenberg. This is the first characterization of the CTX-M-53 ESBL, which represents an additional ceftazidime-hydrolyzing CTX-M enzyme.

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis. A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg x kg(-1) body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period. Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.

Die Spirometrie ist ein hervorragend standardisiertes Messverfahren, mit dem die forcierte Vitalkapazitat (FVC) mit hoher Prazision und Reproduzierbarkeit bestimmt werden kann. Speziell bei Patienten mit idiopathischer pulmonaler Fibrose (IPF) reflektiert die FVC und deren Abfall uber die Zeit den zugrunde liegenden Krankheitsprozess, der durch Vernarbung der Alveolen und Schrumpfung der Lungen charakterisiert ist. Dementsprechend zeigen zahlreiche Studien einen konsistenten Zusammenhang zwischen der Abnahme der FVC im Zeitverlauf und der Mortalitat. Nachdem erstmals wirksame Medikamente zur Therapie der IPF entwickelt wurden, bestatigt sich, dass in Studien, die einen positiven Effekt des Medikaments auf den Abfall der FVC zeigen konnten, auch ein zumindest numerisch positiver Effekt auf die Mortalitat gefunden wurde, wahrend in einer Studie, die keinen signifikanten Effekt auf den Abfall der FVC zeigte, auch die Mortalitat nicht beeinflusst wurde. Insofern kann der Abfall der FVC als Surrogat fur Mortalitat bei IPF-Patienten in prospektiven interventionellen Studien als validiert betrachtet werden. Die FVC-Abnahme ist daher nicht nur ein anerkannter Studienendpunkt, sondern sollte auch fur die Bewertung des patientenrelevanten Nutzens berucksichtigt werden.

Respiratory therapists are healthcare professionals taking care of patients with pulmonary disorders. They are an allied health specialty, practicing under medical direction. The professionalism of nurses and therapists must grow up to act successfully in new fields of medicine, where evidence-based independent action is necessary. Specialized therapists can help us coordinate separated processes (diagnoses, therapy and nursing). The profession "Respiratory Therapist" was created in the United States 50 years ago. We intend to introduce this profession also in Germany. We follow many other countries who have already taken this step. We hope that we can reach yet a higher quality of patient care.

The production of β-lactamases is the predominant cause of resistance to β-lactam antibiotics in gram-negative bacteria. These enzymes cleave the amide bond in the β-lactam ring, rendering β-lactam antibiotics harmless to bacteria. They are classified according to the scheme of Ambler et al. (2) into four classes, designated classes A to D, on the basis of their amino acid sequences, with classes A and C being the most frequently occurring among bacteria. Oxyimino-cephalosporins such as cefotaxime and ceftazidime, which are inherently less susceptible to β-lactamases, were introduced in the early 1980s to treat infections caused by gram-negative bacilli that were resistant to established β-lactams and that produced class A, C, and D β-lactamases. Their repetitive and increased use induced the appearance of resistant strains, which overproduced class C enzymes (42, 72) and/or which produced extended-spectrum β-lactamases (ESBLs), mainly those of class A but also those of class D (19, 61). Class A ESBLs hydrolyze oxyimino-cephalosporins and aztreonam but not 7-α-substituted β-lactams. They are generally susceptible to β-lactamase inhibitors (clavulanate, sulbactam, tazobactam). According to the functional classification scheme of Bush et al. (23), class A ESBLs are therefore clustered in group 2be, which can be subdivided on the basis of their activities against ceftazidime and cefotaxime as ceftazidimases (higher levels of hydrolytic activity against ceftazidime than against cefotaxime) and cefotaximases (higher levels of hydrolytic activity against cefotaxime than against ceftazidime), respectively (48). However, class A ESBLs form a heterogeneous molecular cluster comprising β-lactamases sharing 20 to >99% identity. The earliest class A ESBLs, which were reported from 1985 to 1987, differed from widespread plasmid-mediated TEM-1/2 and SHV-1 penicillinases by one to four point mutations, which extend their hydrolytic spectra (51, 90, 91). TEM and SVH ESBLs now comprise at least 130 members and have a worldwide distribution. Most of them are ceftazidimases, and only a few are cefotaximases. More recently, non-TEM and non-SHV plasmid-mediated class A ESBLs have been reported: ceftazidimases of the PER, VEB, TLA-1, and GES/IBC types and cefotaximases of the SFO-1, BES-1, and CTX-M types (8, 12, 13, 16, 31, 58, 62, 75, 76, 79, 81, 88, 96). The CTX-M β-lactamases are the most widespread enzymes. They were initially reported in the second half of the 1980s, and their rate of dissemination among bacteria and in most parts of the world has increased dramatically since 1995. This review focuses on the origin, epidemiology, clinical impact, enzymatic properties, and structural relationships of the CTX-M-type ESBLs.

Using mean--field improved gauge field configurations, we compare the results obtained for the quark propagator from Wilson fermions and Overlap fermions on a $\3$ lattice at a spacing of $a=0.125(2)$ fm., 5 pages, 8 figures, talk given by F.D.R. Bonnet at LHP 2001 workshop, Cairns, Australia

Background: The tumor microenvironment plays a critical role in cancer development, progression, and control. We demonstrated in vitro and in vivo that a bidirectional crosstalk between tumor-associated macrophages and cancer cells via CCR2-CCL2 and CX3CR1-CXCL1 signaling is fundamental for lung cancer growth and metastasis offers new treatment concepts. Aim: Our working hypothesis is to develop a new platform for specific chemokine receptor (CCR2) PET imaging and a range of theranostic applications in lung cancer. For this purpose, we planned to define the CCR2 expression in NSCLC as well as in SCLC, tumor cells as well as immune/inflammatory cells. Material and Methods: This is a multicenter trial with patients from Zentralklinik Bad Berka GmbH (n =100 NSCLC, n=100 SCLC). All patients gave informed consent according to the declaration of Helsinki. FFPE material was available in all cases. CCR2 CXCR4 and CX3CR1 expression was determined by immunohistochemistry with the avidin-biotin-peroxidase-complex. Results: Analyzing 96 NSCLC (47 adenocarcinoma, 49 squamous cell carcinoma) and 45 SCLC tumor samples, we found CXCR4 and CCR2 chemokine receptor expression in tumor, immune and inflammatory cells. In NSCLC, co-expression between CCR2 and CXCR4 staining was very high concerning their expression on tumor cells rising with higher tumor stages, proliferation rate and grading. CCR2 expression in immune cells was restricted to lower stages; the same pattern could be observed in 45 SCLC tumor samples where CCR2 expression on immune cells was found especially in limited disease rather than in metastatic disease; CXCR4 expression in tumor cells was found to be high in all stages of SCLC. To evaluate the therapeutic efficacy of CCR2 antagonism in vivo, we injected LLC1 s.c. into WT mice treated with CCR2 antagonist (RS504393) or vehicle. Notably, tumor growth was significantly inhibited in CCR2 antagonist-treated mice as compared with vehicle-treated mice. Discussion: Our preliminary results show a significant portion of CCR2 positive tumors - NSCLC as well as SCLC which would qualify for a CCR2-based imaging as well as - demonstrated in our mice models - CCR2 inhibitory strategies. This should be evaluated in further preclinical trials. Citation Format: Katalin Nagy-Major, Jörg Sänger, Harshad R. Kulkarni, Peter Fix, Almut Kunze, Amelie Lupp, Reiner Bonnet, Werner Seeger, Richard P. Baum, Patricia Grabowski, Rajkumar Savai. Chemokine receptor signaling as a new tool to improve lung cancer diagnostics and therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 944. doi:10.1158/1538-7445.AM2017-944

OBJECTIVE: Although radiation therapy is used in early-stage inoperable lung cancer, it often results in injury to functional lung tissue. A study was undertaken to determine the frequency and severity of pulmonary injury revealed by CT in patients who had undergone conformal proton (to a limited volume) radiation therapy. We compared these findings with those from a group of patients who had undergone a combination of photon and conformal proton (to a larger volume) radiation therapy. CONCLUSION: Proton radiation therapy was associated with a lower frequency of pulmonary injury than the combined regimen. Injury correlated well with the volume of normal lung that was irradiated. Conformal proton radiation therapy appears to be able to reduce the incidence and severity of pulmonary injury revealed by CT.

Die idiopathische pulmonale Fibrose (IPF) ist eine schwerwiegende und in der Regel zum Tod fuhrende Erkrankung, die bisher nur unzureichend behandelt werden kann. Empfehlungen zur Diagnostik und Therapie wurden erstmals im ATS-ERS-Statement im Jahr 2000 publiziert 1 . Seither haben sich die diagnostischen Standards geandert und es liegen zahlreiche Therapiestudien zu diesem Krankheitsbild vor, die es erforderlich machten, die bestehenden Empfehlungen zu uberarbeiten und eine wissenschaftlich begrundete Leitlinie zu erstellen. Diese wurde von einer internationalen Expertengruppe in den Jahren 2006 – 2010 erarbeitet und publiziert 2 . Die folgenden Ausfuhrungen beinhalten eine Ubersetzung wesentlicher Inhalte der Originalleitlinie sowie die Interpretation und Adaptation der Empfehlungen an die speziellen Belange des deutschen Gesundheitssystems, wobei auch neue wissenschaftliche Erkenntnisse Berucksichtigung fanden. Die Deutsche Leitlinie zur Diagnostik und Therapie der IPF beruht auf einer Initiative deutscher Experten unter der Schirmherrschaft der Deutschen Gesellschaft fur Pneumologie und Beatmungsmedizin (DGP) und auf den Ergebnissen einer Konsensuskonferenz, die am 3. 12. 2011 in Bochum unter Supervision der „Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)“ abgehalten wurde. Die Mehrzahl der Empfehlungen der internationalen Leitlinie konnten dabei ubernommen werden. Basierend auf aktuellen Studienergebnissen, die zum Zeitpunkt der Verabschiedung der internationalen Leitlinie noch nicht bzw. nicht vollstandig vorlagen wurden die schwach negativen Empfehlungen fur die Antikoagulantientherapie und die Kombinationstherapie mit Prednison, Azathioprin und N-Acteylcystein in stark negative Empfehlungen umgewandelt, wahrend fur Pirfenidon, welches inzwischen in der Europaischen Union zugelassen ist, eine schwach positive Therapieempfehlung ausgesprochen wurde.