Arbeitsmarktwirkungen sind gering: Reformvorschläge zur Grundsicherung für Arbeitsuchende

"Das IAB äußert sich in dieser Stellungnahme zu ausgewählten Aspekten des Gesetzentwurfes der Regierungsfraktionen CDU/CSU und FDP sowie der Anträge der Fraktionen Bündnis 90/Die Grünen, Die Linke und SPD. Sie betreffen die Begründung des Regelbedarfs (insbesondere zur Bestimmung der 'verdeckten Armut'), die neue Hinzuverdienstregelung, die Forderungen nach einem allgemeinen Mindest-lohn, die Förderung der Integration und Teilhabe von Langzeitarbeitslosen am Arbeitsleben, den Vorrang für Ausbildung für Menschen unter 25 Jahren im SGB II und die Einführung eines 'Sozialen Arbeitsmarkts'. Die voraussichtlichen Arbeitsmarktwirkungen, die sich aus der Umsetzung des Entwurfes zu einem Gesetz zur Ermittlung von Regelbedarfen und zur Änderung des Zweiten und Zwölften Buches Sozialgesetzbuch ergeben, sind nach Ansicht des IAB gering. Aus der Regelsatzanpassung resultiert auch keine nennenswerte Verschlechterung der Anreize zur Aufnahme einer Beschäftigung im Niedriglohnbereich. Die Anpassung wird zudem keine größeren fiskalischen Belastungen verursachen. Von der Reform der Freibeträge bei Erwerbstätigkeit im SGB II werden ebenfalls keine signifikanten Arbeitsmarktwirkungen und Zusatzkosten ausgehen." (Autorenreferat)"In this statement, the IAB comments on selected aspects of a draft law submitted by the governing parliamentary parties of the Christian Democrats (CDU/CSU) and Liberals (FDP), and on petitions filed by the Green (Bündnis 90/Die Grünen) and Left (Die Linke) parties and the Social Democrats (SPD). These propositions are concerned with needs for regulation (in particular for the identification of 'concealed' poverty), the new unemployment benefit top-up regulation, claims for a general minimum wage, promotion of the integration and participation of long-term unemployed people in the working life, the priority of education for people under 25 within the scope of the Social Code II, and the introduction of a 'social labour market'. The IAB suggests that foreseeable labour market effects, resulting from the implementation of a law on the identification of benefit recipients’ needs and on changes in the Social Codes II and XII, are rather small. Neither does the adjustment of regu-lation decrease incentives to take up work in the low-wage sector. The adjustment, furthermore, will not create higher fiscal burdens. Neither will the reform of tax exemption (of those topping up Unemployment Benefit II transfers by earnings from minor employment) have significant effects on the labour market or lead to addi-tional costs." (author's abstract

A gain-of-function TBX20 mutation causes congenital atrial septal defects, patent foramen ovale and cardiac valve defects

BACKGROUND: Ostium secundum atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and mutations in cardiac transcription factors, including TBX20, were identified as an underlying cause for ASDII. However, very little is known about disease penetrance in families and functional consequences of inherited TBX20 mutations. METHODS: The coding region of TBX20 was directly sequenced in 170 ASDII patients. Functional consequences of one novel mutation were investigated by surface plasmon resonance, CD spectropolarymetry, fluorescence spectrophotometry, luciferase assay and chromatin immunoprecipitation. RESULTS: We found a novel mutation in a highly conserved residue in the T-box DNA-binding domain (I121M) segregating with CHD in a three generation kindred. Four mutation carriers revealed cardiac phenotypes in terms of cribriform ASDII, large patent foramen ovale or cardiac valve defects. Interestingly, tertiary hydrophobic interactions within the mutant TBX20 T-box were significantly altered leading to a more dynamic structure of the protein. Moreover, Tbx20-I121M resulted in a significantly enhanced transcriptional activity, which was further increased in the presence of co-transcription factors GATA4/5 and NKX2-5. Occupancy of DNA binding sites on target genes was also increased. CONCLUSIONS: We suggest that TBX20-I121M adopts a more fluid tertiary structure leading to enhanced interactions with cofactors and more stable transcriptional complexes on target DNA sequences. Our data, combined with that of others, suggest that human ASDII may be related to loss- as well as gain-of-function TBX20 mutations

Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants

Protease inhibitors (PIs) are important components of treatment regimens for patients with chronic hepatitis C virus (HCV) infection. However, emergence and persistence of antiviral resistance could reduce their efficacy. Thus, defining resistance determinants is highly relevant for efforts to control HCV. Here, we investigated patterns of PI resistance–associated substitutions (RASs) for the major HCV genotypes and viral determinants for persistence of key RASs. We identified protease position 156 as a RAS hotspot for genotype 1‐4, but not 5 and 6, escape variants by resistance profiling using PIs grazoprevir and paritaprevir in infectious cell culture systems. However, except for genotype 3, engineered 156‐RASs were not maintained. For genotypes 1 and 2, persistence of 156‐RASs depended on genome‐wide substitution networks, co‐selected under continued PI treatment and identified by next‐generation sequencing with substitution linkage and haplotype reconstruction. Persistence of A156T for genotype 1 relied on compensatory substitutions increasing replication and assembly. For genotype 2, initial selection of A156V facilitated transition to 156L, persisting without compensatory substitutions. The developed genotype 1, 2, and 3 variants with persistent 156‐RASs had exceptionally high fitness and resistance to grazoprevir, paritaprevir, glecaprevir, and voxilaprevir. A156T dominated in genotype 1 glecaprevir and voxilaprevir escape variants, and pre‐existing A156T facilitated genotype 1 escape from clinically relevant combination treatments with grazoprevir/elbasvir and glecaprevir/pibrentasvir. In genotype 1 infected patients with treatment failure and 156‐RASs, we observed genome‐wide selection of substitutions under treatment. Conclusion : Comprehensive PI resistance profiling for HCV genotypes 1‐6 revealed 156‐RASs as key determinants of high‐level resistance across clinically relevant PIs. We obtained in vitro proof of concept for persistence of highly fit genotype 1‐3 156‐variants, which might pose a threat to clinically relevant combination treatments

Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2–1.0%. Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitorin

Fachkräftebedarf: Analyse und Handlungsstrategien

Mit der verbesserten Lage am Arbeitsmarkt und dem aus demografischen Gründen zu erwartenden Rückgang des Erwerbspersonenpotenzials gewinnt auch das Thema Fachkräftesicherung immer mehr an Bedeutung. Dieses Thema wird in Kapitel D ("Fachkräftebedarf: Analyse und Handlungsstrategien") eingehend behandelt. Dabei wird deutlich: Die Folgen des demografischen Wandels für den Arbeitsmarkt sind erheblich und es muss an vielen Stellschrauben gedreht werden, um diese abzumildern. Sowohl die Mobilisierung inländischer Potenziale als auch die verstärkte Zuwanderung von Fachkräften ist notwendig, um den Rückgang des Erwerbspotenzials spürbar abzufedern

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead