Assessing the Process of Therapeutic Change in the Eating Disorders.

Comparative outcome and process research approaches have not yielded a complete understanding of the beneficial processes of psychotherapy. A recent approach to studying psychotherapy has involved the study of general stages of change that occur during all types of psychotherapy which are positively related to treatment outcome. The purpose of the present investigation was to test a stage of change model for the treatment of the eating disorders anorexia and bulimia nervosa. A review of the literature suggested that there were four general symptom domains that may be related to positive outcome in the treatment of eating disorders. Based on this information a stage of change model was proposed. In order to examine the validity of such a model, a self-report inventory (Eating Disorder Symptom Profile, EDSP) was developed so that the four symptom domains could be assessed at different stages of treatment. Study 1 of this investigation was devoted to the development of the change model and the development of the EDSP. Study 2 involved an examination of the psychometrics of the EDSP, and an initial examination of the stage of change model. Results showed the EDSP to contain 4 factors which were conceptually similar to the 4 symptom areas of the stage of change model. The instrument was found to have good test-retest reliability and moderate to good support for the validity of the EDSP factors. In Study 2, the EDSP was administered to a group of 50 eating disorder patients who were at different points in treatment. The symptom profiles of the EDSP were examined in order to see if they corresponded with predictions made by the stage of change model. Cluster analyses and examination of individual profiles were generally supportive of the model, although the model was not able to account for all patterns of symptomatology evidenced by the patients on the EDSP. Results were discussed with respect to the psychometric characteristics of the EDSP and their implications for testing the stage of change model. Also, suggestions for the refinement of the stage of change model and the EDSP were presented

Validation of Smart Contracts Using Process Mining

Smart contracts are self-executing contracts defining rules for negotiating, verifying the fulfillment of rules and executing the agreement using formal code. They run on top of a blockchain. Errors in smart contracts are costly and are mostly found too late after execution, which is too late for fixing. To improve the validation of executed smart contracts, this paper suggests a process mining based approach. For this, we present an approach for the extraction of meaningful event logs from a blockchain. The event log can be imported in any process mining tool and validation and verification techniques can be used allowing to diagnose (non)conformity in smart contracts by means of common quality measures and with low latency after smart contract execution

Kundenorientierte Wissensaufnahmefähigkeit des Unternehmens: Rückführung des organisationstheoretischen Konstrukts auf eine neurowissenschaftliche Ebene

Kundenorientierung ist ein maßgeblicher Erfolgsfaktor für Unternehmen. Entscheidenden Einfluss hierauf besitzen Mitarbeiter mit Kunden-Kontakt, die sich in Bedürfnisse der Kunden einfühlen können und die ihr Wissen mit anderen Mitarbeitern im Unternehmen teilen. In einem schrittweisen und systematischen Vorgehen werden in dieser Arbeit betriebswirtschaftliche und neurowissenschaftlichen Erkenntnisse zusammengeführt und hierdurch dargelegt, welche Faktoren im Unternehmen diese Gehirnleistung des Einfühlens begünstigen. Die Mehr-Ebenen-Analyse erfolgt ausgehend von der Unternehmensebene, insbesondere Phänomenen der Unternehmenskultur, über die Ebene der Beziehungen zwischen Kunden und Mitarbeitern bis hin zur Ebene des sozialen Gehirns

Comparative psychopathology of women with bulimia nervosa and obsessive-compulsive disorder

Twenty women with bulimia nervosa (BN) and 20 women with obsessive-compulsive disorder (OCD) were compared on responses to the Minnesota Multiphasic Personality Inventory (MMPI), Symptom Checklist-90-Revised (SCL-90-R), and the Beck Depression Inventory (BDI). Multivariate analyses showed no significant differences between bulimic and OCD women on the MMPI, although a greater number of bulimic women showed significant elevations on several of the clinical scales. Analyses of SCL-90-R profiles indicated higher scores on somatization, interpersonal sensitivity, and psychoticism in the BN sample. Bulimic women did not differ significantly from OCD women on either obsessive-compulsive measures or other measures of anxiety. Similarities and differences in symptom profiles between these two groups are discussed, as well as their implications for alternative treatment approaches for BN

Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia Patients Treated With Hypomethylating Agents

Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2mut/ASXL1wt genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNX1mut (Hazard Ratio [HR] = 2.00, p = .011), CBLmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log10(WBC) HR = 2.30, p = .005) independently predicted worse OS while the TET2mut/ASXL1wt predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores CPSS and GFM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX1 mutations. Keywords: Chronic myelomonocytic leukemia, Hypomethylating agents, Somatic mutations, Prognosi

Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from Preleukemic TP53-Mutant Clonal Hematopoiesis

UNLABELLED Low hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (n = 591, ages 18-84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics. The proportion of LH-ALL within Ph-negative B-ALL dramatically increased with age, from 3% in the youngest patients (under 40 years old) to 32% in the oldest (over 55 years old). Somatic TP53 biallelic inactivation was the hallmark of adult LH-ALL, present in virtually all cases (98%). Strikingly, we detected TP53 mutations in posttreatment remission samples in 34% of patients. Single-cell proteogenomics of diagnosis and remission bone marrow samples evidenced a preleukemic, multilineage, TP53-mutant clone, reminiscent of age-related clonal hematopoiesis. SIGNIFICANCE We show that low-hypodiploid ALL is a frequent entity within B-ALL in older adults, relying on somatic TP53 biallelic alteration. Our study unveils a link between aging and low-hypodiploid ALL, with TP53-mutant clonal hematopoiesis representing a preleukemic reservoir that can give rise to aneuploidy and B-ALL. See related commentary by Saiki and Ogawa, p. 102. This article is highlighted in the In This Issue feature, p. 101

Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients

Background: Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Methods: To discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines. Results: In the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7—most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or −7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66–3.86]; P < 0.001; PTPN11: HR, 2.24 [95% CI 1.56–3.22]; P < 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25–4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33–4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30–0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26–0.96]; P = 0.036). Conclusion: This work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation

Genomic characterization of AML with aberrations of chromosome 7:a multinational cohort of 519 patients

Background: Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Methods: To discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines. Results: In the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7—most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or −7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66–3.86]; P &lt; 0.001; PTPN11: HR, 2.24 [95% CI 1.56–3.22]; P &lt; 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25–4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33–4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30–0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26–0.96]; P = 0.036). Conclusion: This work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation.</p

Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn’s disease: an observational study

Background/Objectives: Enteral feeding will induce remission in as many as 80–90% of compliant patients with active Crohn’s disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. Methods/Subjects: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. Results: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. Conclusions: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD