Whole genome sequencing of m. Tuberculosis strains in kazakhstan reveal genomic variants in genes coding pe/ppe protein family specific for mdr/xdr isolates

Worldwide in 2016, around 10.4 million people were diagnosed with TB among which 1.7 million died [1]. Despite the progress in decreasing the global incidence of drug-susceptible TB, multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in the past decade led to decreased efficiency of chemotherapy. However, the rate of drug-resistant TB increases annually, especially multidrug-resistant TB (MDR TB) [1]

Radar target simulator with complex-valued delay line modeling based on standard radar components

With increasing radar activities in the automotive, industrial and private sector, there is a need to test radar sensors in their environment. A radar target simulator can help testing radar systems repeatably. In this paper, the authors present a concept of low-cost hardware for radar target simulation. The theoretical foundations are derived and analyzed. An implementation of a demonstrator operating in the 24&thinsp;GHz ISM band is shown for which the dynamical range simulation was implemented in a FPGA with fast sampling ADCs and DACs. By using a FIR filtering approach a fine discretization of the range could be reached which will furthermore allow an inherent and automatic Doppler simulation by moving the target.</p

The Relationship of Shopping-Related Decisions with Materialistic Values Endorsement, Compulsive Buying-Shopping Disorder Symptoms and Everyday Moral Decision Making

Background: Compulsive buying-shopping disorder (CBSD) is associated with high materialistic values endorsement and excessive purchasing of consumer goods. A subgroup of individuals with CBSD engage in socially unacceptable behaviors to continue shopping despite negative consequences. This investigation aimed at exploring possible links between ego-oriented shopping-related decisions, materialism, symptoms of CBSD and close-to-everyday moral decision making. Methods: In study 1, patients with CBSD were interviewed to develop a list of conflict situations, capturing typical shopping-related dilemmas. In study 2, the shopping-related dilemmas from study 1, standardized close-to-everyday moral dilemmas, the Material Values Scale and Pathological Buying Screener were administered to a web-based convenience sample (n = 274). Results: The main effects of a moderated hierarchical regression analysis revealed an association of more ego-oriented shopping-related decisions with both higher materialistic values endorsement and more CBSD symptoms, but not with everyday moral decision-making. However, a more egoistic everyday moral decision making style moderated the effect of CBSD symptoms on ego-oriented shopping related decisions. Conclusions: The findings indicate that a more egoistic everyday moral decision making style is not directly linked to domain-specific shopping-related decision making but strengthens the link between symptoms of CBSD and ego-oriented shopping-related decisions

Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer.

PURPOSE: R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. PATIENTS AND METHODS: Patients with advanced-stage non–small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. RESULTS: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. CONCLUSION: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial

Background: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95% CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up

POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment

Background: Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting. Methods/design: The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival. Discussion: The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages. Analysis of various outcomes (such as quality of life, physical performance, self-efficacy, psychosocial and immunological parameters) will contribute to a better understanding of the potential of exercise in advanced lung cancer patients. In contrast to other studies with advanced oncological patients the POSITIVE trial provides weekly phone calls to support patients both in the intervention and control group and to segregate the impact of physical activity on quality of life. Trial registration: ClinicalTrials.gov NCT02055508 (Date: December 12, 2013

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Test des neuen PARIO-Gerätes zur automatisierten Schlämmkornanalyse auf Basis der ISP-Methode

Die Partikelgrößenverteilung ("particle size distribution", PSD) kennzeichnet eine der wichtigsten physikalischen Eigenschaften von Böden. Das Referenzverfahren zur Bestimmung des PSD beruht auf der durch Gravitation bedingten Sedimentation von Partikeln in einer anfänglich homogenen Suspension. Herkömmliche Methoden messen manuell (i) den Auftrieb eines schwimmenden Körpers in der Suspension zu verschiedenen Zeiten (Aräometer-Methode) oder (ii) die Feststoffmasse in extrahierten Suspensionsvolumina zu vorgegebenen Zeiten (Pipett-Methode). Beide Verfahren führen zu einer Störung des Sedimentationsprozesses und liefern nur wenige diskrete Daten der PSD. Durner et al. (2017) haben kürzlich eine neue automatisierte Methode zur Bestimmung der Partikelgrößenverteilung von Böden und Sedimenten aus Gravitationssedimentation enwickelt. Das "Integrale Suspensiondruckverfahren" (ISP) schätzt kontinuierliche Partikelgrößenverteilungen aus Sedimentationsexperimenten, indem die zeitliche Entwicklung des Suspensionsdrucks bei einer bestimmten Meßtiefe in einem Sedimentationszylinder aufgezeichnet wird. Das Verfahren erfordert keine manuelle Interaktion nach dem Start und somit keine spezialisierte Ausbildung des Laborpersonals und vermeidet jegliche Störung des Sedimentationsprozesses. Die Technik zur Durchführung dieser Experimente wurde von der Firma UMS AG, München, entwickelt und steht als Instrument mit der Bezeichnung PARIO zur Verfügung, das von der METER Group AG gehandelt wird. In diesem Vortrag wird die grundlegende Funktionsweise von PARIO aufgezeigt und Schlüsselkomponenten und Parameter der Technologie erläutert