Die berufliche Eingliederung von Übersiedlern aus der DDR und Berlin (Ost)

"Im 1. Quartal 1984 konnten 11 800 Personen aus der DDR und Berlin (Ost) in die Bundesrepublik Deutschland übersiedeln, etwa viermal soviel wie im gleichen Zeitraum der vorangegangenen Jahre. Es handelte sich dabei überwiegend um Personen im erwerbsfähigen Alter. Um untersuchen zu können, wie die Eingliederung dieser Personen in das Erwerbsleben bei hoher Arbeitslosigkeit vor sich geht, wurde im Frühjahr 1984 eine Stichprobe von 4100 Übersiedlern gezogen, die sich bei den Arbeitsämtern arbeitslos gemeldet hatten. Diese 4100 Personen wurden Ende 1984, also ca. acht Monate später, über ihren Berufsverlauf seit der Arbeitslosenmeldung und über ihre berufliche Situation befragt. Die Befragung brachte folgende Ergebnisse: 28% der männlichen und 53% der weiblichen Übersiedler waren acht Monate nach ihrer Arbeitslosenmeldung noch oder wieder arbeitslos. Der Anteil ist bei den Frauen auch deshalb wesentlich höher als bei Männern, weil sich weibliche Arbeitslose (vor allem verheiratete, deren Ehemänner erwerbstätig sind und gut verdienen) weniger unter wirtschaftlichem Druck stehend fühlen und sich nach eigenen Angaben bei der Arbeitsuche etwas Zeit lassen können. Fachbarbeiter, Ingenieure und Techniker sowie Ärzte und Apotheker konnten überdurchschnittlich häufig Arbeit finden. Bei Angehörigen der kaufmännischen und Dienstleistungsberufe (z.B. Publizisten, Künstler, Sozialpflegerische Berufe) dagegen liegt der Anteil der Arbeitslosen über dem Durchschnitt. Ein relativ großer Teil der erwerbstätigen Übersiedler mußte angesichts der vorherrschenden Situation auf dem Arbeitsmarkt bei der Arbeitsuche Zugeständnisse machen. So betrachten z.B. 44% ihre jetzige Berufstätigkeit als Übergangslösung, 39% haben nach der Übersiedlung einen Berufswechsel vollzogen, bei 18% ist das Arbeitsverhältnis zeitlich befristet." (Autorenreferat)Übersiedler, berufliche Integration, Arbeitslosigkeit, Berufswechsel, Statusmobilität, beruflicher Status, regionale Mobilität, Berufssituation

On state-alternating context-free grammars

AbstractState-alternating context-free grammars are introduced, and the language classes obtained from them are compared to the classes of the Chomsky hierarchy as well as to some well-known complexity classes. In particular, state-alternating context-free grammars are compared to alternating context-free grammars (Theoret. Comput. Sci. 67 (1989) 75–85) and to alternating pushdown automata. Further, various derivation strategies are considered, and their influence on the expressive power of (state-) alternating context-free grammars is investigated

Immunometabolic Markers in a Small Patient Cohort Undergoing Immunotherapy

Although the discovery of immune checkpoints was hailed as a major breakthrough in can cer therapy, generating a sufficient response to immunotherapy is still limited. Thus, the objective of this exploratory, hypothesis-generating study was to identify potentially novel peripheral biomarkers and discuss the possible predictive relevance of combining scarcely investigated metabolic and hor monal markers with immune subsets. Sixteen markers that differed significantly between responders and non-responders were identified. In a further step, the correlation with progression-free survival (PFS) and false discovery correction (Benjamini and Hochberg) revealed potential predictive roles for the immune subset absolute lymphocyte count (rs = 0.51; p = 0.0224 *), absolute basophil count (rs = 0.43; p = 0.04 *), PD-1+ monocytes (rs = −0.49; p = 0.04 *), hemoglobin (rs = 0.44; p = 0.04 *), metabolic markers LDL (rs = 0.53; p = 0.0224 *), free androgen index (rs = 0.57; p = 0.0224 *) and CRP (rs = −0.46; p = 0.0352 *). The absolute lymphocyte count, LDL and free androgen index were the most significant individual markers, and combining the immune subsets with the metabolic markers into a biomarker ratio enhanced correlation with PFS (rs = −0.74; p ≤ 0.0001 ****). In summary, in addition to well-established markers, we identified PD-1+ monocytes and the free androgen index as potentially novel peripheral markers in the context of immunotherapy. Furthermore, the combination of immune subsets with metabolic and hormonal markers may have the potential to enhance the power of future predictive scores and should, therefore, be investigated further in larger trials

Discrepancy between German S3 Guideline Recommendations and Daily Urologic Practice in the Management of Nonmuscle Invasive Bladder Cancer: Results of a Binational Survey

Introduction: Guideline recommendations are meant to help minimize morbidity and to improve the care of nonmuscle invasive bladder cancer (NMIBC) patients but studies have suggested an underuse of guideline-recommended care. The aim of this study was to evaluate the level of adherence of German and Austrian urologists to German guideline recommendations. Methods: A survey of 27 items evaluating diagnostic and therapeutic recommendations (15 cases of strong consensus and 6 cases of consensus) for NMIBC was administered among 14 urologic training courses. Survey construction and realization followed the checklist for reporting results of internet e-surveys and was approved by an internal review board. Results: Between January 2018 and June 2019, a total of 307 urologists responded to the questionnaire, with a mean response rate of 71%. The data showed a weak role of urine cytology (54%) for initial diagnostics although it is strongly recommended by the guideline. The most frequently used supporting diagnostic tool during transurethral resection of the bladder was hexaminolevulinate (95%). Contrary to the guideline recommendation, 38% of the participants performed a second resection in the case of pTa low-grade NMIBC. Correct monitoring of Bacille Calmette-Guerin (BCG) response with cystoscopy and cytology was performed by only 34% of the urologists. Conclusions: We found a discrepancy between certain guideline recommendations and daily routine practice concerning the use of urine cytology for initial diagnostics, instillation therapy with a low monitoring rate of BCG response, and follow-up care with unnecessary second resection after pTa low-grade NMIBC in particular. Our survey showed a moderate overall adherence rate of 73%. These results demonstrate the need for sharpening awareness of German guideline recommendations by promoting more intense education of urologists to optimize NMIBC care thus decreasing morbidity and mortality rates

Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling

Transferrin receptor 2 (Tfr2) is mainly expressed in the liver and controls iron homeostasis. Here, we identify Tfr2 as a regulator of bone homeostasis that inhibits bone formation. Mice lacking Tfr2 display increased bone mass and mineralization independent of iron homeostasis and hepatic Tfr2. Bone marrow transplantation experiments and studies of cell-specific Tfr2 knockout mice demonstrate that Tfr2 impairs BMP-p38MAPK signaling and decreases expression of the Wnt inhibitor sclerostin specifically in osteoblasts. Reactivation of MAPK or overexpression of sclerostin rescues skeletal abnormalities in Tfr2 knockout mice. We further show that the extracellular domain of Tfr2 binds BMPs and inhibits BMP-2-induced heterotopic ossification by acting as a decoy receptor. These data indicate that Tfr2 limits bone formation by modulating BMP signaling, possibly through direct interaction with BMP either as a receptor or as a co-receptor in a complex with other BMP receptors. Finally, the Tfr2 extracellular domain may be effective in the treatment of conditions associated with pathological bone formation

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% +/- 9.4% vs. 35.4% +/- 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.335.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. Am. J. Hematol., 2012

Approximating Fixation Probabilities in the Generalized Moran Process

We consider the Moran process, as generalized by Lieberman, Hauert and Nowak (Nature, 433:312--316, 2005). A population resides on the vertices of a finite, connected, undirected graph and, at each time step, an individual is chosen at random with probability proportional to its assigned 'fitness' value. It reproduces, placing a copy of itself on a neighbouring vertex chosen uniformly at random, replacing the individual that was there. The initial population consists of a single mutant of fitness $r>0$ placed uniformly at random, with every other vertex occupied by an individual of fitness 1. The main quantities of interest are the probabilities that the descendants of the initial mutant come to occupy the whole graph (fixation) and that they die out (extinction); almost surely, these are the only possibilities. In general, exact computation of these quantities by standard Markov chain techniques requires solving a system of linear equations of size exponential in the order of the graph so is not feasible. We show that, with high probability, the number of steps needed to reach fixation or extinction is bounded by a polynomial in the number of vertices in the graph. This bound allows us to construct fully polynomial randomized approximation schemes (FPRAS) for the probability of fixation (when $r\geq 1$) and of extinction (for all $r>0$).Comment: updated to the final version, which appeared in Algorithmic

Rectal Indomethacin Dose Escalation (RIDE) for Prevention of Post-ERCP Pancreatitis in High-Risk Patients: a Randomized Trial

Background Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. Methods In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. Findings Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients—76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87–1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients—six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. Interpretation Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP