Supervision und Coaching - Gemeinsamkeiten und Unterschiede hinsichtlich von Kontrakt, Setting und Arbeitsbündnis

In diesem Beitrag werden Konzepte und die Gestaltung von Beratungsprozessen, so wie sie sich vor allem aus den Selbstauskünften der DGSv und der Internetauftritte des Deutschen Berufsverbandes Coaching (DBCV) herausfiltern lassen, aufgelistet und miteinander verglichen. Im Fokus der Betrachtung stehen dabei inhaltliche und normative Unterschiede. In diesem Zusammenhang wird zunächst eine Begriffsbestimmung von Coaching und Supervision vorgenommen und die Entwicklungslinien des Coaching herausgearbeitet. Des Weiteren werden der Kontrakt, das Setting und das Arbeitsbündnis im Coaching und in der Supervision beleuchtet

Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer – the multinational MATEO study

Background: The optimal duration of firstline chemotherapy in metastatic esophagogastric cancer is unknown. In most clinical trials therapy was given until tumour progression or limiting toxicity. Maintenance concepts aiming to prolong the duration of response and maintain quality of life have been established in other tumour types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Methods: The Maintenance Teysuno® (S-1) in esophagogastric cancer (MATEO) trial is a multinational, randomized phase II study that explores the role of S-1 maintenance therapy in Her-2 negative, advanced esophagogastric adenocarcinoma. After a 12-week firstline platinum-fluoropyrimidine-based chemotherapy patients without tumour progression are randomized in a 2:1 allocation to receive S-1 alone or continue with the same regimen as during the primary period. The primary endpoint is overall survival. Secondary endpoints include safety and toxicity, progression-free survival and quality of life. Correlative biomarker analyses focus on the identification of a subgroup of patients with a prolonged benefit from S-1 based maintenance therapy. Discussion: MATEO will be the first trial to define the role of a S-1 based maintenance therapy in patients having received a platinum-based firstline chemotherapy. Trial registration: NCT02128243 (date of registration: 29–04-2014)

Integrating patient reported measures as predictive parameters into decisionmaking about palliative chemotherapy: a pilot study

Background: Systemic treatment has proven to improve physical symptoms in patients with advanced cancer. Relationship between quality of life (QoL) or symptom burden (SYB) and treatment efficacy (tumour response and survival) is poorly described. Therefore, we evaluated the predictive value of pretreatment QoL and SYB on treatment outcomes. Methods: Eligible patients had metastatic gastrointestinal cancers and were about to receive 1st/2nd line palliative chemotherapy. 47 patients were consecutively enrolled. QoL and SYB were assessed by EORTC QLQ-C30 and MSKCC MSAS questionnaires before treatment and after first response evaluation after 8–12 weeks. Logistic regression analysis of QoL and SYB for prediction of objective treatment efficacy was performed. Patients were categorized according to response rate (RR) based on RECIST1.1 and progression free survival (PFS). PFS was categorized by a ratio (individual PFS/expected PFS) in above median (ratio > 1) or below median PFS (ratio 10 points difference). Lowest scores in all functioning scales at treatment start were seen in patients with future PFSR < 1. Global health status (EORTC), PSYCH subscale and global distress index (MSAS) predicted PFSR, even if adjusted for gender, age, cancer type, ECOG and line of treatment (p < 0.05). Interestingly, improved QoL and SYB (subjective benefit) were noted even in patients with worse pretreatment status and no objective tumour response. Conclusion: Future non-responders seem to show distinct QoL patterns before chemotherapy. This may facilitate early detection of patients deriving less or even no benefit from treatment regarding prolongation of survival. Even in patients with primarily progressive disease QoL and SYB may improve during treatment. Integration of QoL and SYB assessment into decision-making about palliative chemotherapy seem to be an important approach to improve patient outcome and should be further evaluated

Botrydial and botcinins produced by Botrytis cinerea regulate the expression of Trichoderma arundinaceum genes involved in trichothecene biosynthesis

Trichoderma arundinaceum IBT 40837 (Ta37) and Botrytis cinerea produce the sesquiterpenes harzianum A (HA) and botrydial (BOT), respectively, and also the polyketides aspinolides and botcinins (Botcs), respectively. We analysed the role of BOT and Botcs in the Ta37–B. cinerea interaction, including the transcriptomic changes in the genes involved in HA (tri) and ergosterol biosynthesis, as well as changes in the level of HA and squaleneergosterol. We found that, when confronted with B. cinerea, the tri biosynthetic genes were up-regulated in all dual cultures analysed, but at higher levels when Ta37 was confronted with the BOT non-producer mutant bcbot2D. The production of HA was also higher in the interaction area with this mutant. In Ta37– bcbot2D confrontation experiments, the expression of the hmgR gene, encoding the 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is the first enzyme of the terpene biosynthetic pathway, was also up-regulated, resulting in an increase in squalene production compared with the confrontation with B. cinerea B05.10. Botcs had an up-regulatory effect on the tri biosynthetic genes, with BotcA having a stronger effect than BotcB. The results indicate that the interaction between Ta37 and B. cinerea exerts a stimulatory effect on the expression of the tri biosynthetic genes, which, in the interaction zone, can be attenuated by BOT produced by B. cinerea B05.10. The present work provides evidence for a metabolic dialogue between T. arundinaceum and B. cinerea that is mediated by sesquiterpenes and polyketides, and that affects the outcome of the interaction of these fungi with each other and their environment

Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

BACKGROUND: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. METHODS: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. RESULTS: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7-13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60-76%) and FP/FA (0-77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0-16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10-10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. CONCLUSION: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage

Trichothecenes and aspinolides produced by Trichoderma arundinaceum regulate expression of Botrytis cinerea genes involved in virulence and growth

Trichoderma arundinaceum (Ta37) and Botrytis cinerea (B05.10) produce the sesquiterpenoids harzianum A (HA) and botrydial (BOT), respectively. TaDTri5, an HA non-producer mutant, produces high levels of the polyketide compounds aspinolides (Asp) B and C. We analyzed the role of HA and Asp in the B. cinerea-T. arundinaceum interaction, including changes in BOT production as well as transcriptomic changes of BcBOT genes involved in BOT biosynthesis, and also of genes associated with virulence and ergosterol biosynthesis. We found that exogenously added HA up-regulated the expression of the BcBOT and all the virulence genes analyzed when B. cinerea was grown alone. However, a decrease in the amount of BOT and a down-regulation of BcBOT gene expression was observed in the interaction zone of B05.10- Ta37 dual cultures, compared to TaDTri5. Thus, the confrontation with T. arundinaceum results in an upregulation of most of the B. cinerea genes involved in virulence yet the presence of T. arundinaceum secondary metabolites, HA and AspC, act separately and together to down-regulate the B. cinerea genes analyzed. The present work emphasizes the existence of a chemical cross-regulation between B. cinerea and T. arundinaceum and contributes to understanding how a biocontrol fungus and its prey interact with each other

Algebraic characteristic classes for idempotent matrices

This paper contains the algebraic analog for idempotent matrices of the Chern-Weil theory of characteristic classes. This is used to show, algebraically, that the canonical line bundle on the complex projective space is not stably trivial. Also a theorem is proved saying that for any smooth manifold there is a canonical epimorphism from the even dimensional algebraic de Rham cohomology of its algebra of smooth functions onto the standard even dimensional de Rham cohomology of the manifold

Fungicide-Driven Evolution and Molecular Basis of Multidrug Resistance in Field Populations of the Grey Mould Fungus Botrytis cinerea

The grey mould fungus Botrytis cinerea causes losses of commercially important fruits, vegetables and ornamentals worldwide. Fungicide treatments are effective for disease control, but bear the risk of resistance development. The major resistance mechanism in fungi is target protein modification resulting in reduced drug binding. Multiple drug resistance (MDR) caused by increased efflux activity is common in human pathogenic microbes, but rarely described for plant pathogens. Annual monitoring for fungicide resistance in field isolates from fungicide-treated vineyards in France and Germany revealed a rapidly increasing appearance of B. cinerea field populations with three distinct MDR phenotypes. All MDR strains showed increased fungicide efflux activity and overexpression of efflux transporter genes. Similar to clinical MDR isolates of Candida yeasts that are due to transcription factor mutations, all MDR1 strains were shown to harbor activating mutations in a transcription factor (Mrr1) that controls the gene encoding ABC transporter AtrB. MDR2 strains had undergone a unique rearrangement in the promoter region of the major facilitator superfamily transporter gene mfsM2, induced by insertion of a retrotransposon-derived sequence. MDR2 strains carrying the same rearranged mfsM2 allele have probably migrated from French to German wine-growing regions. The roles of atrB, mrr1 and mfsM2 were proven by the phenotypes of knock-out and overexpression mutants. As confirmed by sexual crosses, combinations of mrr1 and mfsM2 mutations lead to MDR3 strains with higher broad-spectrum resistance. An MDR3 strain was shown in field experiments to be selected against sensitive strains by fungicide treatments. Our data document for the first time the rising prevalence, spread and molecular basis of MDR populations in a major plant pathogen in agricultural environments. These populations will increase the risk of grey mould rot and hamper the effectiveness of current strategies for fungicide resistance management