Wenig Transparenz bei den Kosten

Über die weiter steigenden medizinischen Kosten wird viel diskutiert. Aber wie sieht es mit den nicht-medizinischen Kosten in Spitälern aus? Ein Projekt der ZHAW versucht Transparenz zu schaffen

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology

Binary Fluorescence Labeling for the Recovery of Polymeric Materials for Recycling

Fluorescent perylene derivatives for the invisible digital coding of polymers were reported where a binary combination of fluorescent doping allows the unambiguous identification of the polymers for sorting. The mono-material recovery of the polymeric materials is an important prerequisite for the high-performance application of recycled material and was enabled by the application of optical methods

Indications for liver transplantation in adults

Liver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics

A gene expression profile associated with relapse of cytogenetically normal acute myeloid leukemia is enriched for leukemia stem cell genes

Some 50 – 80% of patients with acute myeloid leukemia (AML) achieve a complete remission with contemporary chemotherapy protocols, yet the majority of them eventually relapse with resistant disease: some patients no longer respond to chemotherapy at disease recurrence; others accomplish second and even third remissions whose decreasing duration nevertheless indicates that the pool of residual leukemic cells, i.e. of cells that persisted during treatment with cytotoxic drugs, increases with every round of therapy [1]. Either of these clinical courses therefore refl ects an enhanced chemotherapy resistance of leukemic cells at relapse as compared to the cell population at diagnosis. Molecular changes enabling malignant cells to survive exposure to cytotoxic drugs may already have been present in a subset of the leukemic cell population at presentation, or may emerge during treatment [2,3], but in any case are thought to be selected as a consequence of drug therapy, and to play a major role in therapy resistance at relapse. Remarkably, however, even though various types of molecular alterations may be acquired at relapse, neither specifi c cytogenetic alterations nor functionally relevant point mutations as identifi ed by whole genome sequencing were associated with relapse in a recurrent manner [2,3]. Certain copy number variations and known AML associated point mutations were newly present at relapse in small proportions of patients (usually 10%), but the latter were lost in other patients, indicating that they are unlikely to represent drivers of therapy resistance at disease recurrence [4]. Th ese fi ndings could either indicate that chemotherapy resistance at relapse is acquired through a large variety of different mechanisms, or that molecular changes of other types than those mentioned above are of more general relevance in this context. Indeed, an earlier study has suggested that the expression of specifi c genes may change in a consistent manner between diagnosis and relapse of AML [5]. However, only a limited number of genes and mostly unpaired samples were probed in this investigation. Th erefore, in the present study, genes whose expression changed in a relapse-specifi c manner were sought in a set of paired AML samples and on a genome-wide scale. To limit the genetic heterogeneity of the study population, only samples from patients with cytogenetically normal (CN) AML were used.Letter to the Edito

Measurement of an Elongation of the Pion Source in Z Decays

We measure Bose-Einstein correlations between like-sign charged pion pairs in hadronic Z decays with the L3 detector at LEP. The analysis is performed in three dimensions in the longitudinal center-of-mass system. The pion source is found to be elongated along the thrust axis with a ratio of transverse to longitudinal radius of $0.81\pm 0.02 ^{+0.03}_{-0.19}$

Glioblastoma in the oldest old: Clinical characteristics, therapy, and outcome in patients aged 80 years and older

Background: Incidence rates of glioblastoma in very old patients are rising. The standard of care for this cohort is only partially defined and survival remains poor. The aims of this study were to reveal current practice of tumor-specific therapy and supportive care, and to identify predictors for survival in this cohort. Methods: Patients aged 80 years or older at the time of glioblastoma diagnosis were retrospectively identified in 6 clinical centers in Switzerland and France. Demographics, clinical parameters, and survival outcomes were annotated from patient charts. Cox proportional hazards modeling was performed to identify parameters associated with survival. Results: Of 107 patients, 45 were diagnosed by biopsy, 30 underwent subtotal resection, and 25 had gross total resection. In 7 patients, the extent of resection was not specified. Postoperatively, 34 patients did not receive further tumor-specific treatment. Twelve patients received radiotherapy with concomitant temozolomide, but only 2 patients had maintenance temozolomide therapy. Fourteen patients received temozolomide alone, 35 patients received radiotherapy alone, 1 patient received bevacizumab, and 1 took part in a clinical trial. Median progression-free survival (PFS) was 3.3 months and median overall survival (OS) was 4.2 months. Among patients who received any postoperative treatment, median PFS was 3.9 months and median OS was 7.2 months. Karnofsky performance status (KPS) ≥70%, gross total resection, and combination therapy were associated with better outcomes. The median time spent hospitalized was 30 days, accounting for 23% of the median OS. End-of-life care was mostly provided by nursing homes (n = 20; 32%) and palliative care wards (n = 16; 26%). Conclusions: In this cohort of very old patients diagnosed with glioblastoma, a large proportion was treated with best supportive care. Treatment beyond surgery and, in particular, combined modality treatment were associated with longer OS and may be considered for selected patients even at higher ages

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness