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To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy.VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy.The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%).Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.

Unsere zunehmende Abhängigkeit von Informationstechnik erhöht kontinuierlich die Safety- und Security-Anforderungen bei deren Einsatz. Ein zentrales Problem hierbei sind Schwachstellen von Hard- und Software. Marktkräfte konnten diese Situation bislang nicht grundsätzlich beheben. Eine Gegenstrategie sollte deshalb folgende Optionen erwägen: (1) private und staatliche Förderung offener und sicherer IT‑Produktion, (2) Verbesserung der souveränen Kontrolle bei der Produktion aller kritischen IT‑Komponenten innerhalb eines Wirtschaftsraumes sowie (3) verbesserte und durchgesetzte Regulierung. Dieser Beitrag analysiert Vor- und Nachteile dieser Optionen. Es wird vorgeschlagen, die Sicherheit der Schlüsselkomponenten einer Lieferkette durch weltweit verteilte, offene und ggf. mathematisch bewiesene Komponenten zu gewährleisten. Der beschriebene Ansatz erlaubt die Nutzung existierender und neuer proprietärer Komponenten. Increasing dependence on information technology calls for strengthening the requirements on their safety and security. Vulnerabilities that result from flaws in hardware and software are a core problem which market mechanisms have failed to eliminate. A strategy for resolving this issue should consider the following options: (1) private- and public-sector funding for open and secure production, (2) strengthening the sovereign control over the production of critical IT components within an economic zone, and (3) improving and enforcing regulation. This paper analyses the strengths and weaknesses of these options and proposes a globally distributed, secure supply chain based on open and mathematically proved components. The approach supports the integration of legacy and new proprietary components.

Kurzfassung: Wie kann effektive Deutsche Cyberabschreckung aussehen? Dieser Artikel stellt die ersten Ergebnisse eines neuen Cyberabschreckungsmodells vor, genannt „Agile Cyberabschreckung“, das auf interdisziplinärer Forschung am ISPK basiert. Danach eröffnen Cyber-Operationen einen völlig neuen Weg in der Verteilung von Macht. Grundsätzlich dafür ist der spezielle virtuelle (technologische) Charakter der operativen Domäne „Cyber“. Die beschriebene Agile Cyberabschreckung adressiert die spezifischen Cyber-Verwundbarkeiten einer „Cyber-Mittel-Macht“ wie Deutschland und schlägt vier Abschreckungsoptionen vor.

Zurich, Switzerland S. Kruger & B. Hattendorf You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to B. Hattendorf. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is the solution to the Analytical Challenge to be found at https://doi.org/10.1007/s00216-020-02459-1 Reprints and Permissions Kruger, S., Hattendorf, B. Solution to element crossword challenge. Anal Bioanal Chem 412, 6635–6636 (2020). https://doi.org/10.1007/s00216-020-02877-1 Download citation Published: 10 September 2020 Issue Date: October 2020 DOI: https://doi.org/10.1007/s00216-020-02877-1

The ability to disperse is considered essential for soil bacteria colonization and survival, yet very little is known about the dispersal ability of communities from different heterogeneous soil compartments. Important factors for dispersal are the thickness and connectivity of the liquid film between soil particles. The present results from a fractured clay till depth profile suggest that dispersal ability is common in various soil compartments and that most are dominated by a few dispersing taxa. Importantly, an increase in shared dispersers among the preferential flow paths of the clay till suggests that active dispersal plays a role in the successful colonization of these habitats., This study assessed the dispersal of five bacterial communities from contrasting compartments along a fractured clay till depth profile comprising plow layer soil, preferential flow paths (biopores and the tectonic fractures below), and matrix sediments, down to 350 cm below the surface. A recently developed expansion of the porous surface model (PSM) was used to capture bacterial communities dispersing under controlled hydration conditions on a soil-like surface. All five communities contained bacteria capable of active dispersal under relatively low hydration conditions (−3.1 kPa). Further testing of the plow layer community revealed active dispersal even at matric potentials of −6.3 to −8.4 kPa, previously thought to be too dry for dispersal on the PSM. Using 16S rRNA gene amplicon sequencing, the dispersing communities were found to be less diverse than their corresponding total communities. The dominant dispersers in most compartments belonged to the genus Pseudomonas and, in the plow layer soil, to Rahnella as well. An exception to this was the dispersing community in the matrix at 350 cm below the surface, which was dominated by Pantoea. Hydrologically connected compartments shared proportionally more dispersing than nondispersing amplicon sequence variants (ASVs), suggesting that active dispersal is important for colonizing these compartments. These results highlight the importance of including soil profile heterogeneity when assessing the role of active dispersal and contribute to discerning the importance of active dispersal in the soil environment. IMPORTANCE The ability to disperse is considered essential for soil bacteria colonization and survival, yet very little is known about the dispersal ability of communities from different heterogeneous soil compartments. Important factors for dispersal are the thickness and connectivity of the liquid film between soil particles. The present results from a fractured clay till depth profile suggest that dispersal ability is common in various soil compartments and that most are dominated by a few dispersing taxa. Importantly, an increase in shared dispersers among the preferential flow paths of the clay till suggests that active dispersal plays a role in the successful colonization of these habitats.

In this study, we developed a method that provides profiles of community-level surface dispersal from environmental samples under controlled hydration conditions and enables us to isolate and uncover the diversity of the fastest bacterial dispersers. The method expands on the porous surface model (PSM), previously used to monitor the dispersal of individual bacterial strains in liquid films at the surface of a porous ceramic disc. The novel procedure targets complex communities and captures the dispersed bacteria on a solid medium for growth and detection. The method was first validated by distinguishing motile Pseudomonas putida and Flavobacterium johnsoniae strains from their nonmotile mutants. Applying the method to soil and lake water bacterial communities showed that community-scale dispersal declined as conditions became drier. However, for both communities, dispersal was detected even under low-hydration conditions (matric potential, −3.1 kPa) previously proven too dry for P. putida strain KT2440 motility. We were then able to specifically recover and characterize the fastest dispersers from the inoculated communities. For both soil and lake samples, 16S rRNA gene amplicon sequencing revealed that the fastest dispersers were substantially less diverse than the total communities. The dispersing fraction of the soil microbial community was dominated by Pseudomonas species cells, which increased in abundance under low-hydration conditions, while the dispersing fraction of the lake community was dominated by Aeromonas species cells and, under wet conditions (−0.5 kPa), also by Exiguobacterium species cells. The results gained in this study bring us a step closer to assessing the dispersal ability within complex communities under environmentally relevant conditions. IMPORTANCE Dispersal is a key process of bacterial community assembly, and yet, very few attempts have been made to assess bacterial dispersal at the community level, as the focus has previously been on pure-culture studies. A crucial factor for dispersal in habitats where hydration conditions vary, such as soils, is the thickness of the liquid films surrounding solid surfaces, but little is known about how the ability to disperse in such films varies within bacterial communities. Therefore, we developed a method to profile community dispersal and identify fast dispersers on a rough surface resembling soil surfaces. Our results suggest that within the motile fraction of a bacterial community, only a minority of the bacterial types are able to disperse in the thinnest liquid films. During dry periods, these efficient dispersers can gain a significant fitness advantage through their ability to colonize new habitats ahead of the rest of the community.

Glass-ceramics are noted for their unusual combination of properties and manifold commercialized products for consumer and specialized markets. Evolution of novel glass and ceramic processing routes, a plethora of new compositions, and unique exotic nano- and microstructures over the past 60 years led us to review the definition of glass-ceramics. Well-established and emerging processing methods, such as co-firing, additive manufacturing, and laser patterning are analyzed concerning the core requirements of processing glass-ceramics and the performance of the final products. In this communication, we propose a revised, updated definition of glass-ceramics, which reads “Glass-ceramics are inorganic, non-metallic materials prepared by controlled crystallization of glasses via different processing methods. They contain at least one type of functional crystalline phase and a residual glass. The volume fraction crystallized may vary from ppm to almost 100%”.

The goal of this study was to examine the development of the reticulum, rumen, omasum and abomasum in six calves from birth to 100 days of age by means of six serial ultrasonographic examinations. The examinations were carried out in standing animals using a 5 MHz-transducer as described previously. The calves were primarily fed milk until examination 4 and then they were weaned. The reticulum was assessed for its shape and contractility, the rumen for its size and content, the omasum for its size, content and motility and the abomasum for its size and content before and after the ingestion of milk. The reticulum was seen in all calves starting at examination 2 and had biphasic and triphasic contractions; the latter were associated with eructation. The rumen was always imaged in all calves as early as Day 1 and its visible size increased progressively in all intercostal spaces (ICSs) during the study period. The omasum was best imaged in the 8th or 9th ICS; it was seen medial to the liver dorsally and usually medial to small intestines ventrally. Its visible size in these two ICSs increased progressively but omasal motility was not apparent. In newborn calves the abomasum was the largest compartment and dominated the abdominal cavity. It was visible from the 5th ICS to the flank. Except for examination 2, the mean visible abomasal length was significantly larger after feeding than before. Lateral abomasal extension to the left was greater than to the right at examinations 1-4, but was much smaller than to the right at examinations 5 and 6 because of progressive expansion of the rumen. Abomasal extension into the right hemiabdomen changed little during the study period.

[1] Fluid-induced seismicity results from an activation of finite rock volumes. The finiteness of perturbed volumes influences frequency-magnitude statistics. Previously we observed that induced large-magnitude events at geothermal and hydrocarbon reservoirs are frequently underrepresented in comparison with the Gutenberg-Richter law. This is an indication that the events are more probable on rupture surfaces contained within the stimulated volume. Here we theoretically and numerically analyze this effect. We consider different possible scenarios of event triggering: rupture surfaces located completely within or intersecting only the stimulated volume. We approximate the stimulated volume by an ellipsoid or cuboid and derive the statistics of induced events from the statistics of random thin flat discs modeling rupture surfaces. We derive lower and upper bounds of the probability to induce a given-magnitude event. The bounds depend strongly on the minimum principal axis of the stimulated volume. We compare the bounds with data on seismicity induced by fluid injections in boreholes. Fitting the bounds to the frequency-magnitude distribution provides estimates of a largest expected induced magnitude and a characteristic stress drop, in addition to improved estimates of the Gutenberg-Richter a and b parameters. The observed frequency-magnitude curves seem to follow mainly the lower bound. However, in some case studies there are individual large-magnitude events clearly deviating from this statistic. We propose that such events can be interpreted as triggered ones, in contrast to the absolute majority of the induced events following the lower bound.

Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium.Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation.Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372).Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.

Fe isotope ratios and concentrations of dissolved Fe (Fedis, < 0.45 μm) and of suspended particulate Fe (FeSPM) were analyzed from a depth profile through the anoxic Eastern Gotland Basin water column, Baltic Sea. Results show a sharp gradient in δ56Fedis across the ferruginous layer with δ56Fedis = −0.4‰ in the euxinic deep basin and δ56Fedis = &plus;0.3‰ in the oxic upper water column. The isotopic gradient overlaps with a strong concentration gradient of Fedis, a concentration maximum in FeSPM and lower δ56FeSPM values than δ56Fedis. These features indicate preferential loss of light Fe isotopes from solution to suspended iron-oxyhydroxides (FeIOH) during typical oxidative precipitation across the redox interface. The sign of the overall fractionation, Δ56FeIOH-Fe(II)(aq) < 0‰, is in contrast to similar, mostly non-marine redox environments, where Δ56FeIOH-Fe(II)(aq) > 0‰. The difference appears to be the result of isotope exchange dominated by reaction kinetics in the marine water column, rather than equilibrium fractionation generally inferred for oxidative Fe precipitation elsewhere. High residual δ56Fedis immediately above the oxic–ferruginous interface and throughout the oxic water column suggests that any potential dissolved Fe export from marine reducing waters into the oxic open water column is enriched in the heavy isotopes. In the deep, mildly euxinic water column above the level of Fe sulfide saturation, a decreasing δ56FeSPM trend with depth and a generally low δ56Fedis are comparable to trends generally observed in marine anoxic sediment profiles where microbial reductive Fe dissolution occurs. The isotope composition of the redox-cycled Fe inventory in anoxic marine basins mainly reflects the balance between external fluxes, driving the composition towards crustal δ56Fe values, and intensity of internal recycling, driving δ56Fe towards negative values.

Summary Background Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. Methods In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam–Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. Findings We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (−0·03 points [4·04]; −0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. Interpretation 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. Funding German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

The present study explores the temperature and time dependence of heterogeneous crystal nucleation in a lithium disilicate glass using the stochastic approach. In particular a single lithium disilicate sample was repeatedly (284 runs) undercooled to 1173 K in a PtRh-crucible and the crystallization onset time during an isothermal hold was detected in each run. The statistical distribution of the times elapsed before crystallization is described by a first order reaction with a heterogeneous crystal nucleation rate of (9.19 ± 0.04) × 10-4 s-1 while individually shaped crystallization exotherms of each run were recorded which indicate growth of a single or only few crystals during crystallization of the entire volume. The data were used together with results of previous stochastic experiments and those of double-stage heat treatments to calculate the crystallization time of a fraction of 10-4 percent for all temperatures between glass transition and melting. The derived TTT diagram shows a double nose of crystallization in the volume at large undercoolings (0.53–0.61 Tm) and crystallization at the surface at small undercoolings (0.62–0.92 Tm) initiated by homogeneous and heterogeneous crystal nucleation, respectively. The critical cooling rate at the heterogeneous nose is approximately 73 K s-1.

Li₃.₅Y₁.₅(MoO₄)₄ was synthesized in the form of phase-pure crystals. It forms a solid solution with Li₃.₅Eu₁.₅(MoO₄)₄. Single crystals obtained from Li₂MoO₄ fluxes had edge lengths of up to 0.5 mm. The crystal structures of Li₃.₅(Y₁₋ₓEuₓ)₁.₅(MoO₄)₄ (x = 0, 0.1, 0.25, 0.5, 0.75 and 1) were determined in the triclinic crystal system (e.g. P1, no. 2, Z = 1; Li₃.₅Y₁.₅(MoO₄)₄: a = 5.1875(2) Å, b = 6.6380(2) Å, c = 10.2731(4) Å, α = 100.082(3)°, β = 100.257(2)° and γ = 111.943(2)°). All the compounds are isostructural and crystallize with a structure related to the scheelite-type structure with mixed occupancy of one cation position, while the two others are occupied by Li ions exclusively. Thermal analyses reveal stability in air up to 995 K for Li₃.₅Y₁.₅(MoO₄)₄; the decomposition temperature decreases with an increase in Eu-content. Spectroscopic properties (emission and excitation) were investigated in the context of the search for new thermographic phosphors. Excitation at 395 nm leads to strong red emission at 613 nm. Features of the emission spectra suggest the potential of Li₃.₅(Y₁₋ₓEuₓ)₁.₅(MoO₄)₄ as red phosphor candidates for light emitting diodes. Their luminescence properties at high temperatures were also investigated.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Background Respiratory infection and failure is a commonly encountered problem in intensive care unit (ICU) patients. However, despite the accumulating body of evidence to suggest that herpes simplex virus type 1 (HSV-1) is associated with pneumonia, the exact role played by this virus in this process is still not fully understood. Therefore, to identify patients at risk, we have conducted a case–control study to characterize patients with HSV-1-positive pneumonia. Patients and methods Between 2007 and 2009, all patients with suspected viral pneumonia were tested for the presence of herpes viruses using a PCR assay approach with respiratory specimens. To identify possible associations, risk factors, and impact of HSV, HSV-1-positive ICU patients (n = 51) were compared to age-, gender-, and department- and season-matched HSV-negative patients (n = 52). Results HSV-positive patients differed significantly from the HSV-negative ones only in terms of time of mechanical ventilation (13 vs. 6 days, respectively; p = 0.002). Subgroup analysis in the patients aged >60 years and in those without bacterial detection revealed a similar trend (p = 0.01 and p = 0.004, respectively). Mortality did not differ between the groups or between the HSV-1-positive patients treated with aciclovir and those who were not. A viral load >10E+05 geq/ml was associated with mechanical ventilation (20/21 vs. 17/29; p = 0.004), acute respiratory distress syndrome (ARDS; 19/21 vs. 18/29; p = 0.005), sepsis (18/21 vs. 14/29; p = 0.008), detection of a bacterial pathogen in the same specimen (10/21 vs. 4/29; p = 0.01) and longer ICU stay (25 vs. 30 days; p = 0.04). Conclusion Despite several associations with high viral load, the clinical outcome of HSV-1-positive ICU patients did not differ significantly from the clinical outcome of HSV-negative patients. This finding indicates that HSV-1 viral loads in respiratory specimens are a symptom of a clinically poor condition rather than a cause of it. Longitudinal and therapy studies are therefore needed to distinguish between HSV-1 as a causative pathogen and HSV-1 as a bystander of pneumonia/ARDS.

INTRODUÇÃO: A orientação dietética e o uso adequado de quelantes de fósforo são a base do tratamento da hiperfosfatemia. Assim, seu sucesso depende essencialmente da habilidade do paciente em entender e aderir ao plano dietético e ao uso dos quelantes. OBJETIVO: Avaliar a adesão e o conhecimento de pacientes hiperfosfatêmicos em hemodiálise sobre o tratamento da hiperfosfatemia. METODOLOGIA: Estudo transversal. Foram incluídos 112 pacientes em hemodiálise (60 homens; idade = 49,3 ± 13,3 anos), de cinco unidades de diálise, que apresentaram média de fósforo sérico > 5,5 mg/dL entre julho e dezembro de 2008 (média = 6,57 ± 0,73 mg/dL). Foi aplicado um questionário que incluía questões fechadas sobre consequências da hiperfosfatemia, alimentos ricos em fósforo, uso adequado dos quelantes e opinião do paciente sobre os motivos do insucesso do tratamento. Os parâmetros laboratoriais avaliados foram: fósforo, cálcio, paratormônio e ureia séricos, e a eficiência da diálise por meio do Kt/V. RESULTADOS : A média de acertos das questões do questionário foi de 78,5%. Com relação às razões do insucesso do tratamento da hiperfosfatemia, 87% dos pacientes assinalaram a resposta "porque eu como mais fósforo do que eu deveria" e/ ou "porque eu não tomo o quelante de fósforo como eu deveria". Entre os que afirmaram não utilizar o quelante corretamente, a maioria (62%) justificou o esquecimento como motivo. O fósforo sérico correlacionou-se diretamente com a ureia sérica (R = 0,33; p < 0,01) e inversamente com o Kt/V (R = -0,20; p < 0,05). Não houve correlação entre a fosfatemia, o nível de escolaridade e a pontuação no questionário. CONCLUSÃO: Os pacientes estudados apresentaram um bom nível de conhecimento sobre o tratamento da hiperfosfatemia, mas a maioria afirmou não ser aderente ao mesmo. Estratégias para melhorar a adesão ao tratamento são necessárias para diminuir a ocorrência da hiperfosfatemia nessa população.INTRODUCTION: Adequate dietary phosphorus intake and the use of phosphorus binders are the main tools for treating hyperphosphatemia. Thus, its success depends essentially on the patient's ability to understand and adhere to the dietary plan and the use of phosphate binders. OBJECTIVE: To evaluate hyperphosphatemic patients adherence and knowledge about phosphate control treatment. METHODS: This is a cross-sectional study. One hundred and twelve patients on hemodialysis (60 males; age = 49.3 ± 13.3 years), from five dialysis centers with mean serum phosphorus > 5.5 mg/dL between July and December of 2008 (mean = 6.57 ± 0.73 mg/dL) were included. A questionnaire with questions about the consequences of hyperphosphataemia, foods high in phosphorus, appropriate use of phosphate binders and patient's opinion about reasons for treatment failure was administered. Laboratory parameters assessed were serum urea, calcium, phosphorus and parathormony (PTH), and dialysis adequacy by means of urea Kt/V. RESULTS: The average score of questionnaire was 78.5%. Regarding the reasons for the failure of the treatment of hyperphosphataemia, 87% indicated the response "because I eat more phosphorus than I should" and / or "because I do not take the phosphate binder as I should". Among those who said they did not use phosphate binder correctly, most (62%) justified to forget as the reason. The serum phosphorus correlated directly with serum urea (R = 0.33, p < 0.01) and inversely with Kt/V (R = -0.20, p < 0.05). There was no correlation between the phosphorus, the education level and the scores on questionnaire. CONCLUSION: Patients showed a good level of knowledge about the hyperphosphatemia treatment, but the vast majority were noncompliant to that. Strategies to improve compliance are necessary to decrease the incidence of hyperphosphatemia in hemodialysis patients.

PURPOSE: The study was performed to evaluate an intensified breast cancer screening program for women at risk of familial breast cancer. MATERIAL UND METHODS: 157 women were included in the study. Criteria for inclusion were: proven mutation of the BRCA 1-gene (n = 33), BRCA 2-gene (n = 14), heterozygous risk of ≥ 20 % or lifetime risk for developing breast cancer of ≥ 30 % (n = 110). Results were evaluated separately for healthy women and women with a history of breast or ovarian cancer. The study protocol consisted of 6-monthly clinical examinations as well as ultrasound and yearly mammography and MR-mammography. RESULTS: 12 women were diagnosed with breast cancer during the observation period (1. 11. 1999-31. 10. 2007); 75 % of the carcinomas were pT1-lesions, 89 % were pN0-lesions. The sensitivity of clinical examination was 25 % (mammography 27 %, ultrasound 58 %, MR-mammography 100 %). The positive predictive value was 75, 38, 50 and 60 % and specificity was 99,8, 99,6, 99,0, 97,6 %, respectively. These data are in accordance with the results of other national and international studies. The detection rate of carcinoma and positive predictive value were highest for carriers of BRCA 1-gene mutations. CONCLUSION: Based on the published data, implementing intensified screening programs for women at risk of familial breast cancer leads to the detection of carcinoma at an early stage. MR-mammography was shown to be the most sensitive method with acceptable positive predictive value. Further studies need to be performed to determine the perfect interval between examinations.

The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) risk classes.

Freehand positioning of the femoral drill guide is difficult during hip resurfacing and the surgeon is often unsure of the implant position achieved peroperatively. The purpose of this study was to find out whether, by using a navigation system, acetabular and femoral component positioning could be made easier and more precise. Eighteen patients operated on by the same surgeon were matched by sex, age, BMI, diagnosis and ASA score (nine patients with computer assistance, nine with the regular ancillary). Pre-operative planning was done on standard AP and axial radiographs with CT scan views for the computer-assisted operations. The final position of implants was evaluated by the same radiographs for all patients. The follow-up was at least 1 year. No difference between both groups in terms of femoral component position was observed (p > 0.05). There was also no difference in femoral notching. A trend for a better cup position was observed for the navigated hips, especially for cup anteversion. There was no additional operating time for the navigated hips. Hip navigation for resurfacing surgery may allow improved visualisation and hip implant positioning, but its advantage probably will be more obvious with mini-incisions than with regular incision surgery.

The objective of this study was to investigate the impact of a hunting trip on hunters‟ quality of life (QoL) as measured by life domains. A number of life domains that are directly related to a hunting trip may affect the QoL of hunters. A web-based survey was conducted and 158 responses were received. The statistical analysis consisted of descriptive statistics of the demographic profile of hunters, Cronbach‟s alpha, mean-inter-item-correlations, mean/standard deviation and a structural equation model. The results have indicated that social and travel life domains have a statistically significant effect on life domains overall, as well as on the QoL of hunters on a hunting trip as measured by life domains. The main contributions of the research are twofold: Firstly, it makes a contribution to the current literature on hunters and QoL; and secondly, it has identified the intangible aspects of hunting that may be used by owners of hunting products in marketing a hunting trip.

The article presents the outline of a comparative framework for the understanding of religious fundamentalism. The argument is developed around the interrelated aspects of macro-historical religious context, socio-religious context, and the context of religious tradition as a primary dimension of religion. In those overlapping contexts, the possibility of fundamentalism is explained with refe-rence to pre-disposing, precipitating and perpetuating conditions. In terms of the dimension of religious tradition, fundamentalism is expounded in terms of the following three aspects: education, inter-pretation and identity-definition. Fundamentalism emerges as an awkward mix (not a creative synthesis) of traditional and modernist elements in the present breach - with its peculiar characteristics, crises and threats - between epochs.

The nearly complete, PCR-amplified, 16S rRNA gene sequences have been determined from the representative type strains of eight xanthomonad phena, including six validly described species of the genus Xanthomonas and Stenotrophomonas maltophilia. Pairwise sequence comparisons and phylogenetic analysis demonstrated that the xanthomonads comprise a monophyletic lineage-within the gamma-subclass of the Proteobacteria. Although the genus Xanthomonas was observed to comprise a cluster of very closely related species, the observed species-specific primary sequence differences were confirmed through sequencing additional strains belonging to the respective species.

SUMMARY Scattering and diffraction of elastic waves by many cracks or inclusions have a significant influence on the waves behaviour (e.g. velocity, attenuation). As a result of the lack of an analytical solution for scattering caused by complex crack structures, numerical methods have to be used to compute the wave field. The numerical error of such methods has to be controlled. In this paper, we present an accuracy analysis of the rotated staggered grid (RSG)—finite difference (FD) scheme. It is designed, amongst other things, to model wave propagation in multiple cracked rocks with high contrasts in their elastic moduli without implementing explicit boundary conditions and without averaging elastic moduli (e.g. at free surfaces like crack boundaries). The problem of a plane SH wave scattered by a single finite crack has a known analytical solution. This solution provides a chance to validate the special abilities of the RSG–FD scheme. The calculation precision is examined by comparing numerical and analytical results. We observe a very good agreement for the single finite crack. Because the RSG is not restricted to the single crack case only, we conclude that this approach is an accurate tool to study wave propagation in media with many cracks.

This paper is concerned with numerical considerations of fluid effects on wave propagation. The focus is on effective elastic properties (i.e. velocities) in different kinds of dry and fluid-saturated fractured media. We apply the so-called rotated staggered finite-difference grid (RSG) technique. Using this modified grid it is possible to simulate the propagation of elastic waves in a 2D or 3D medium containing cracks, pores or free surfaces without explicit boundary conditions and without averaging elastic moduli. Therefore the RSG allows an efficient and precise numerical study of effective velocities in fractured structures. This is also true for structures where theoretically it is only possible to predict upper and lower bounds. We simulate the propagation of plane P- and S-waves through three kinds of randomly cracked 3D media. Each model realization differs in the porosity of the medium and is performed for dry and fluid-saturated pores. The synthetic results are compared with the predictions of the well known Gassmann equation and the Biot velocity relations. Although we have a very low porosity in our models, the numerical calculations showed that the Gassmann equation cannot be applied for isolated pores (thin penny-shaped cracks). For Fontainebleau sandstone we observe with our dynamic finite-difference approach the exact same elastic properties as with a static finite-element approach. For this case the Gassmann equation can be checked successfully. Additionally, we show that so-called open-cell Gaussian random field models are an useful tool to study wave propagation in fluid-saturated fractured media. For all synthetic models considered in this study the high-frequency limit of the Biot velocity relations is very close to the predictions of the Gassmann equation. However, using synthetic rock models saturated with artificial ``heavy' water we can roughly estimate the corresponding tortuosity parameter.

Hintergrund: Das endobronchiale Lipom ist ein sehr seltener benigner Lungentumor. Als Therapiemoglichkeiten bestehen die interventionelle bronchoskopische Therapie oder die chirurgische Resektion. Methoden: In den Jahren 1996 bis 2002 wurden in unserer Klinik 16 Patienten mit einem endobronchialen Lipom diagnostiziert. Wir untersuchten die klinischen Daten der Patienten und deren Einfluss auf die gewahlte Therapie. Ergebnisse: Von den 16 Patienten (60 ± 14 J.) waren 14 mannlich (88 %). Die klinischen Symptome waren Husten (81 %), Dyspnoe (75 %), Infiltrat (63 %) und Fieber (31 %). In der rechten Lunge fanden sich 11 Lipome (69 %), in der linken 5 (31 %). Die Verteilung auf Hauptbronchus, Ober-, Mittel- und Unterlappen war 2 (12,5 %), 6 (37,5 %), 2 (12,5 %) und 6 (37,5 %). 14 (88 %) Lipome fanden sich in den zentralen Atemwegen, 2 waren peripher gelegen. Von den zentral gelegenen Lipomen konnten alle erfolgreich mittels bronchoskopischer Lasertherapie behandelt werden. Dazu waren im Mittel 1,1 ± 0,3 Lasersitzungen erforderlich. Ein Patient verstarb an einem gleichzeitig vorliegenden Bronchial-Karzinom vor Therapie. Eine chirurgische Sanierung war nur bei einem sehr peripher gelegenen grosen Lipom und einem Parenchym destruierend wachsenden Lipom erforderlich. Schlussfolgerungen: Die bronchoskopische Resektion sollte als Therapie der ersten Wahl beim endobronchialen Lipom eingesetzt werden. Sie ist sicher, erfolgreich, schneller durchfuhrbar und preisgunstiger als die chirurgische Therapie. Die chirurgische Therapie ist lediglich indiziert bei Patienten mit destruierendem oder sehr peripherem Wachstum, extrabronchialem Wachstum, der Moglichkeit eines malignen Tumors oder technischen Schwierigkeiten bei der bronchoskopischen Prozedur. Background: Endobronchial lipoma is a very rare benign lung tumor. Therapeutic alternatives are the interventional bronchoscopic laser resection or surgical treatment. Methods: From 1996 to 2002 we diagnosed 16 patients with endobronchial lipoma in our institution. We examined the clinical data of the patients and their influence on the individual patient treatment. Results: 14 (88 %) out of the 16 patients (60 ± 14 y.) were male. Clinical symptoms were cough (81 %), dyspnea (75 %), pulmonary infiltration (63 %) and fever (31 %). In the right lung 11 lipomas (69 %) were located, in the left lung 5 lipomas (31 %). The distribution to main bronchus, upper lobe, middle lobe and lower lobe bronchus were 2 (12.5 %), 6 (37.5 %), 2 (12.5 %) und 6 (37.5 %). 14 (88 %) lipomas were found in the central airways, 2 were located in the periphery of the lung. All lipomas in the central airways were successfully treated by bronchoscopic laser therapy with a mean of 1.1 ± 0.3 laser sessions. One patient died of concomitant bronchial carcinoma before therapy. Surgical treatment was only necessary in a very peripherally located huge lipoma and a lipoma with extensive parenchym destruction. Conclusions: Bronchoscopic laser resection should be considered as first line therapy in cases of endobronchial lipoma. It is safe, successful, rapid and less expensive compared to surgical resection. Surgery should only be indicated in patients with lipomas with very peripherally localisation or parenchym destruction, extrabronchial growth, suspected malignancy or technical problems at bronchoscopic resection.

Summary Background : Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease. Aims : To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease. Methods : We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters. Results : In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01). Conclusions : Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.

Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.

Recurrent focal myositis is a rare entity and can be difficult to diagnose and treat. A long-term follow-up and diagnostic evaluation was carried out in a patient who presented with ankle stiffness secondary to a painful mass within the calf. This process was diagnosed as focal myositis of the peroneal muscles, which recurred over a period of 7 yr. A review of the literature regarding focal myositis, treatment options and a successful conservative therapy regimen, as an alternative to a surgical protocol, are presented. After making the diagnosis with the help of a muscle biopsy, long-term therapy should be considered. Conservative treatment of focal myositis with anti-inflammatory drugs and physical therapy can be successful but recurrence may occur if the medical treatment is interrupted.

Ultrasonography of a six-year-old Simmental cow revealed an abscess like structure, approximately 15 cm in diameter, in place of the right kidney. The cow had a history of colic for 4 days and was referred to our clinic with a tentative diagnosis of caecal dilatation. The cow voided dark opaque urine with white floccules. Laboratory examination yielded increased haematocrit, leukocytosis with left shift, hyperbilirubinaemia and azotaemia. The diagnosis was confirmed, the caecum emptied surgically and the pus-filled structure at the site of the right kidney removed. A diagnosis of pyonephrosis was made after pathological examination of the pus-filled structure.Bei einer 6 Jahre alten Fleckviehkuh wurde mittels Ultraschalluntersuchung anstelle der rechten Niere ein ca. 15 cm grosses abszessartiges Gebilde gefunden. Die Kuh hatte seit 4 Tagen Anzeichen von Kolik gezeigt und war mit der Verdachtsdiagnose Blinddarmdilatation in die Klinik eingewiesen worden. Die Blinddarmdilatation konnte bestätigt werden. Der Spontanharn war dunkelgelb und trüb mit weisslichen Flocken. Im Blut wurden ein erhöhter Hämatokrit, eine Leukozytose mit Linksverschiebung, eine Hyperbilirubinämie und eine Azotämie festgestellt. Die Kuh wurde operiert. Dabei wurden der Blinddarm entleert und das mit Eiter gefüllte Gebilde entfernt. Bei der pathologisch-anatomischen Untersuchung stellte sich heraus, dass es sich dabei um eine Pyonephrose handelte.

Ultrasonography of a six-year-old Simmental cow revealed an abscess like structure, approximately 15 cm in diameter, in place of the right kidney. The cow had a history of colic for 4 days and was referred to our clinic with a tentative diagnosis of caecal dilatation. The cow voided dark opaque urine with white floccules. Laboratory examination yielded increased haematocrit, leukocytosis with left shift, hyperbilirubinaemia and azotaemia. The diagnosis was confirmed, the caecum emptied surgically and the pus-filled structure at the site of the right kidney removed. A diagnosis of pyonephrosis was made after pathological examination of the pus-filled structure.