Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib

The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 × 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 × 10(9)/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier:00055874).

Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV

PURPOSE Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.

Gilui ha-niqhudh. Revelelatio punctationis : dissertatio

Leiden, Univ., Diss., 1680

Assessment of STR Typing Success Rate in Soft Tissues from Putrefied Bodies Based on a Quantitative Grading System for Putrefaction.

To date, there is no systematic investigation of the association of short tandem repeat (STR) typing success rate in soft tissues with different signs of putrefaction. Herein, putrefaction was rated using a newly developed 19-parameter system in soft tissues from a collective of 68 decaying bodies, and DNA yield was determined in 408 samples. DNA integrity was rated using a self-devised pentaplex PCR generating an "integrity score" (Si ). STR typing success rate was then assessed for selected cases. DNA yield and Si differed significantly between tissues with kidney on average exhibiting the highest Si values. Statistical analysis revealed that nine parameters were significantly and positively correlated with Si . The observed values for each of these nine parameters were summed up to generate a putrefaction score (Sp ) for each sample. Our results show that STR typing success rate can be predicted based on Sp before expensive multiplex STR profiling is performed.

Three essays on the concept of trust and its foundations

The present dissertation focuses on trust and comprises three empirical essays on the concept itself and its foundations. All three essays investigate trust as an expectation and rely on selfreport measures of trust. Whereas the first two chapters investigate social trust, the third chapter investigates political trust. Essentially, there are three related important debates to which the following chapters contribute. A first debate discusses problems with current selfreport measures. Scholars recently started to question whether standard trust questions really measure the same across countries and languages. Chapter 1 engages in this debate. Using data from Switzerland it studies whether different trust questions measure the same latent trust constructs across individuals belonging to three different culturallinguistic regions. The second debate concerns the socalled forms or dimensions of trust. Recently, scholars started investigating whether trust is a onedimensional construct, i.e. whether an individual's trust judgment differs for categories of trustees such as strangers, neighbors, family members and friends or not. Relying on confirmatory factor analysis Chapter 2 investigates whether individuals really do make a difference between different trustee categories and to what extent these judgments can be summarized into higherorder latent trust constructs. The third debate is concerned with causes of differences in trust across humans. Chapter 3 focuses on the role of laterlife experiences, more precisely victimization experiences and investigates their causal relationship with generalized social trust. Chapter 4 focuses on the impact of direct democratic institutions on the trust relationship between citizens and political authorities.

Simultaneous analysis of nuclear and mitochondrial DNA, mRNA and miRNA from backspatter from inside parts of firearms generated by shots at "triple contrast" doped ballistic models

When a firearm projectile hits a biological target a spray of biological material (e.g., blood and tissue fragments) can be propelled from the entrance wound back towards the firearm. This phenomenon has become known as "backspatter" and if caused by contact shots or shots from short distances traces of backspatter may reach, consolidate on, and be recovered from, the inside surfaces of the firearm. Thus, a comprehensive investigation of firearm-related crimes must not only comprise of wound ballistic assessment but also backspatter analysis, and may even take into account potential correlations between these emergences. The aim of the present study was to evaluate and expand the applicability of the "triple contrast" method by probing its compatibility with forensic analysis of nuclear and mitochondrial DNA and the simultaneous investigation of co-extracted mRNA and miRNA from backspatter collected from internal components of different types of firearms after experimental shootings. We demonstrate that "triple contrast" stained biological samples collected from the inside surfaces of firearms are amenable to forensic co-analysis of DNA and RNA and permit sequence analysis of the entire mtDNA displacement-loop, even for "low template" DNA amounts that preclude standard short tandem repeat DNA analysis. Our findings underscore the "triple contrast" method's usefulness as a research tool in experimental forensic ballistics.

Interpersonale Konsequenzen von offenen Selbstgesprächen in Dyaden im Sport

In der sportpsychologischen Forschung werden sowohl offene als auch verdeckte Selbstgespräche mehrheitlich als rein intrapersonale Phänomene betrachtet und sowohl deren Antezedenzien als auch Konsequenzen nur auf die mit sich selbst sprechende Person bezogen untersucht. Erste laborexperimentelle Studien, die die Effekte von offenen Selbstgesprächen auf die Eindrucksbildung (Graf, Lier & Seiler, 2012; Van Raalte, Brewer, Cornelius & Petitpas, 2006) und die individuelle Leistung (Gould & Weiss, 1981) eines Beobachters nachweisen konnten und Aussagen verschiedener Tennisspieler (Rimmer, Greenlees, Graydon, Thelwell & Buscombe, 2008), dass sie die offene Selbstgespräche der Gegner bei der Bildung eines ersten Eindrucks verwenden würden, deuten jedoch auf die Bedeutsamkeit von interpersonalen Konsequenzen von offenen Selbstgesprächen hin. Um das Verständnis für die interpersonalen Konsequenzen von offenen Selbstgesprächen im Sport zu vertiefen, wurden zwei Studien mit unterschiedlicher Methodik durchgeführt. In einer qualitativen Feldstudie wurden mit 13 Badmintonspielern im Anschluss an ihr Badminton Herren-Doppel Selbstkonfrontationsinterviews durchgeführt, um die Wahrnehmungsergebnisse nach offenen, während eines realen Wettkampfes geäusserten Selbstgesprächen zu untersuchen. Die wahrgenommenen positiven, negativen und motivierenden Selbstgespräche führten zu Zuschreibungen von mentalen Zuständen und Kognitionen und vereinzelt zur Einschätzung des episodischen Leistungsvermögens. Weiter lösten die Selbstgespräche verschiedene affektive Reaktionen und Erwartungsreaktionen aus, deren mögliche Konsequenzen für den weiteren Spielverlauf diskutiert werden. Um einzelne Resultate aus dieser ersten Studie eingehender zu analysieren (zugeschriebene Kompetenz und stellvertretende Valenzeinschätzung; Birrer & Seiler, 2008), und zur Untersuchung der Effekte der offenen Selbstgespräche auf die individuelle Leistung eines Teampartners wurde eine zweite, laborexperimentelle Studie durchgeführt. Zur Herstellung der drei experimentellen Bedingungen kam ein gleichgeschlechtlicher Konfident zum Einsatz, der als vermeintlicher Teampartner fungierte und der während der Golf-Putt-Aufgabe als Reaktion auf die eigenen Putts positive, negative oder keine Selbstgespräche führte. Bezogen auf die zugeschriebene Kompetenz zeigte sich kein allgemeiner, sondern ein von der Valenz der Probanden bedingter Effekt der negativen Selbstgespräche: War den Probanden die Aufgabe wichtig, führten negative Selbstgespräche zur Zuschreibung einer tiefen Kompetenz. Weiter lösten sowohl positive als auch negative Selbstgespräche die Einschätzung aus, dass dem Partner die Aufgabe wichtig ist. Keine Effekte hatten die Selbstgespräche auf die individuelle Leistung der Probanden. Explorativ durchgeführte Nachanalysen deuten jedoch darauf hin, dass sich die Selbstgespräche des Partners womöglich nach einer gewissen Zeit auf die individuelle Leistung der wahrnehmenden Person auswirken könnten, weshalb methodische Anpassungen diskutiert werden, mit Hilfe derer der Effekt der Selbstgespräche auf die Leistung gesteigert werden könnte. Neben den hypothesenprüfenden Tests ermittelten verschiedene Post-Hoc-Analysen aufschlussreiche Resulate (z.B. zu affektiven Reaktionen). Die Ergebnisse der beiden Studien bringen klar zum Ausdruck, dass die interpersonale Perspektive bei der Erforschung der Effekte von offenen Selbstgesprächen bedeutsame Erkenntnisse für Theorie und Praxis liefern kann.

Josef deutet den Traum Pharaos [Illustration]

P. von Cornelius

Wiedererkennung Josefs [Illustration]

P. von Cornelius

De Republica Hebraeorum, commentario illustratus opera Constantini l'Empereur ab Oppijck

Vorlage d. Digitalisats aus d. Besitz d. Theol. Hochschule St. Georgen

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 417 - Übersetzungen lateinischer Redewendungen

u.a.: vorwiegend aus den Urtexten von Livius; Plinius; Tacitus; Cicero; Terenz; Horaz;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 416 - Übersetzungen lateinischer Redewendungen

u.a.: vorwiegend aus den Urtexten von Tacitus; Livius; Cicero; Seneca;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 423 - Zitatensammlung aus Seneca, Plinius, Martial, Cicero, Tacitus, Lucretius

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