Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial

Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.

Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility.

Otium et negotium. Reading processes and their cultural backgrounds in early Italian and German humanism

Reading and reading habits have radically changed in the digital age. Readers are no longer physically bound to textual objects and libraries, they deal with texts by copying, altering, and annotating them, and they mix established textual forms with other semiotic systems such as pictograms, icons and images. These circumstances also provoke a renewed research interest in the history of reading. In this talk, I will concentrate on reading processes as to how they were enacted and practised in early Italian and German humanism. I will start with some paradigmatic scenes described in Petrarch’s letters (among others the famous visit of the Mont Ventoux, where Petrarch, after having enjoyed a spectacular panorama, withdraws into the contemplative reading of St-Augustine). The transmission of Petrarch’s writings in humanist circles of Southern Germany (e.g. with the Schedel and Gossembrot families in Nurnberg, Augsburg and Strasburg) will then lead to specific reading practices documented in manuscripts that once belonged to coherent libraries and are nowadays spread all over Europe. In the case of the former tradesman and mayor Sigismund Gossembrot, complex habits of textual annotating and cross-referencing can be observed. The dichotomy of the Latin terms otium (‘rest’ and ‘leisure’) and negotium (‘activity’, but also ‘practice’, ‘negotiation’, ‘circulation of social energy’ in the sense of New Historicism) will be used as an ideal-type outline to describe the occurring processes of reading.

Otium et negotium. Reading processes and their cultural backgrounds in early Italian and German humanism

Reading and reading habits have radically changed in the digital age. Readers are no longer physically bound to textual objects and libraries, they deal with texts by copying, altering, and annotating them, and they mix established textual forms with other semiotic systems such as pictograms, icons and images. These circumstances also provoke a renewed research interest in the history of reading. In this talk, I will concentrate on reading processes as to how they were enacted and practised in early Italian and German humanism. I will start with some paradigmatic scenes described in Petrarch’s letters (among others the famous visit of the Mont Ventoux, where Petrarch, after having enjoyed a spectacular panorama, withdraws into the contemplative reading of St-Augustine). The transmission of Petrarch’s writings in humanist circles of Southern Germany (e.g. with the Schedel and Gossembrot families in Nurnberg, Augsburg and Strasburg) will then lead to specific reading practices documented in manuscripts that once belonged to coherent libraries and are nowadays spread all over Europe. In the case of the former tradesman and mayor Sigismund Gossembrot, complex habits of textual annotating and cross-referencing can be observed. The dichotomy of the Latin terms otium (‘rest’ and ‘leisure’) and negotium (‘activity’, but also ‘practice’, ‘negotiation’, ‘circulation of social energy’ in the sense of New Historicism) will be used as an ideal-type outline to describe the occurring processes of reading.

Prognostic value of the modified American College of Cardiology/American Heart Association lesion morphology classification for clinical outcome after sirolimus-eluting stent placement (results of the prospective multicenter German Cypher Registry)

The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology classification scheme has prognostic impact for early and late outcomes when bare-metal stents are used. Its value after drug-eluting stent placement is unknown. The predictive value of this lesion morphology classification system in patients treated using sirolimus-eluting stents included in the German Cypher Registry was prospectively examined. The study population included 6,755 patients treated for 7,960 lesions using sirolimus-eluting stents. Lesions were classified as type A, B1, B2, or C. Lesion type A or B1 was considered simple (35.1%), and type B2 or C, complex (64.9%). The combined end point of all deaths, myocardial infarction, or target vessel revascularization was seen in 2.6% versus 2.4% in the complex and simple groups, respectively (p = 0.62) at initial hospital discharge, with a trend for higher rates of myocardial infarction in the complex group. At the 6-month clinical follow-up and after adjusting for other independent factors, the composite of cumulative death, myocardial infarction, and target vessel revascularization was nonsignificantly different between groups (11.4% vs 11.2% in the complex and simple groups, respectively; odds ratio 1.08, 95% confidence interval 0.8 to 1.46). This was also true for target vessel revascularization alone (8.3% of the complex group, 9.0% of the simple group; odds ratio 0.87, 95% confidence interval 0.72 to 1.05). In conclusion, the modified ACC/AHA lesion morphology classification system has some value in determining early complications after sirolimus-eluting stent implantation. Clinical follow-up results at 6 months were generally favorable and cannot be adequately differentiated on the basis of this lesion morphology classification scheme.

Variation in fat mobilization during early lactation differently affects feed intake, body condition, and lipid and glucose metabolism in high-yielding dairy cows.

Fat mobilization to meet energy requirements during early lactation is inevitable because of insufficient feed intake, but differs greatly among high-yielding dairy cows. Therefore, we studied milk production, feed intake, and body condition as well as metabolic and endocrine changes in high-yielding dairy cows to identify variable strategies in metabolic and endocrine adaptation to overcome postpartum metabolic load attributable to milk production. Cows used in this study varied in fat mobilization around calving, as classified by mean total liver fat concentrations (LFC) postpartum. German Holstein cows (n=27) were studied from dry off until d 63 postpartum in their third lactation. All cows were fed the same total mixed rations ad libitum during the dry period and lactation. Plasma concentrations of metabolites and hormones were measured in blood samples taken at d 56, 28, 15, and 5 before expected calving and at d 1 and once weekly up to d 63 postpartum. Liver biopsies were taken on d 56 and 15 before calving, and on d 1, 14, 28, and 49 postpartum to measure LFC and glycogen concentrations. Cows were grouped accordingly to mean total LFC on d 1, 14, and 28 in high, medium, and low fat-mobilizing cows. Mean LFC (±SEM) differed among groups and were 351±14, 250±10, and 159±9 mg/g of dry matter for high, medium, and low fat-mobilizing cows, respectively, whereas hepatic glycogen concentrations postpartum were the highest in low fat-mobilizing cows. Cows in the low group showed the highest dry matter intake and the least negative energy balance postpartum, but energy-corrected milk yield was similar among groups. The decrease in body weight postpartum was greatest in high fat-mobilizing cows, but the decrease in backfat thickness was greatest in medium fat-mobilizing cows. Plasma concentrations of nonesterified fatty acids and β-hydroxybutyrate were highest around calving in high fat-mobilizing cows. Plasma triglycerides were highest in the medium group and plasma cholesterol concentrations were lowest in the high group at calving. During early lactation, the decrease in plasma glucose concentrations was greatest in the high group, and plasma insulin concentrations postpartum were highest in the low group. The revised quantitative insulin sensitivity check index values decreased during the transition period and postpartum, and were highest in the medium group. Plasma cortisol concentrations during the transition period and postpartum period and plasma leptin concentrations were highest in the medium group. In conclusion, cows adapted differently to the metabolic load and used variable strategies for homeorhetic regulation of milk production. Differences in fat mobilization were part of these strategies and contributed to the individual adaptation of energy metabolism to milk production.

Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [<200mg of total fat/g of dry matter (DM); n=10], medium (200-300 mg of total fat/g of DM; n=10), and high (>300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable gene expression depending on LFC after parturition. Correlations between hepatic gene expression and performance data and plasma concentrations of metabolites and hormones showed time-specific relations during the transition period. Elevated body fat mobilization during early lactation affected gene expression involved in gluconeogenesis to a greater extent than gene expression involved in lipid metabolism, indicating the dependence of hepatic glucose metabolism on hepatic lipid status and fat mobilization during early lactation.

Early versions in medieval textual traditions. Wolfram’s Parzival as a test case

Wolfram von Eschenbach’s novel Parzival is a courtly romance composed in German language shortly after 1200. In a project, based at the University of Bern, a new critical edition of the poem is prepared in electronic and printed form. It visualizes parallel textual versions, which, depending on particular circumstances of oral performance, have developed in the early stage of the poem’s transmission. Philological research as well as phylogenetic techniques common in the natural sciences, e.g. in molecular biology, have been used to demonstrate the existence of these early textual versions. The article shows how both methods work and how they are applied to the ongoing edition. Exemplary passages to be presented include the text of some rare fragments written in the first decades of the 13th century, which might even go back to the author’s lifetime and which allow to date the existence of the versions they belong to.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Reversal of gender differences in Educational Attainment – historical analysis of the West German Case

Background information: During the late 1970s and the early 1980s, West Germany witnessed a reversal of gender differences in educational attainment, as females began to outperform males. Purpose: The main objective was to analyse which processes were behind the reversal of gender differences in educational attainment after 1945. The theoretical reflections and empirical evidence presented for the US context by DiPrete and Buchmann (Gender-specific trends in the value of education and the emerging gender gap in college completion, Demography 43: 1–24, 2006) and Buchmann, DiPrete, and McDaniel (Gender inequalities in education, Annual Review of Sociology 34: 319–37, 2008) are considered and applied to the West German context. It is suggested that the reversal of gender differences is a consequence of the change in female educational decisions, which are mainly related to labour market opportunities and not, as sometimes assumed, a consequence of a ‘boy’s crisis’. Sample: Several databases, such as the German General Social Survey, the German Socio-economic Panel and the German Life History Study, are employed for the longitudinal analysis of the educational and occupational careers of birth cohorts born in the twentieth century. Design and methods: Changing patterns of eligibility for university studies are analysed for successive birth cohorts and gender. Binary logistic regressions are employed for the statistical modelling of the individuals’ achievement, educational decision and likelihood for social mobility – reporting average marginal effects (AME). Results: The empirical results suggest that women’s better school achievement being constant across cohorts does not contribute to the explanation of the reversal of gender differences in higher education attainment, but the increase of benefits for higher education explains the changing educational decisions of women regarding their transition to higher education. Conclusions: The outperformance of females compared with males in higher education might have been initialised by several social changes, including the expansion of public employment, the growing demand for highly qualified female workers in welfare and service areas, the increasing returns of women’s increased education and training, and the improved opportunities for combining family and work outside the home. The historical data show that, in terms of (married) women’s increased labour market opportunities and female life-cycle labour force participation, the raising rates of women’s enrolment in higher education were – among other reasons – partly explained by their rising access to service class positions across birth cohorts, and the rise of their educational returns in terms of wages and long-term employment.

Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

UNLABELLED Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. RESULTS (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.