Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874.

Historische Entwicklungen im Wohlfahrtswesen der Schweiz

In diesem Handbuch werden Themen, Handlungsfelder und Organisationen des Schweizer Sozialwesens «sichtbar» gemacht: historische Entwicklungen, aktuelle Herausforderungen, Abhängigkeiten und Zusammenhänge. Fachpersonen aus den Organisationen des Schweizer Sozialwesens sowie Wissenschaftler und Wissenschaftlerinnen aus Hochschulen zeigen auf, welchen Einfluss Entscheidungen in der Sozial- und Bildungspolitik auf die Lebensverhältnisse der Bevölkerung haben und welchen Beitrag das Sozialwesen an das Wohl aller leistet. Exemplarisch verdeutlicht werden die Besonderheiten des Schweizer Sozialwesens anhand der Sozialversicherungen, der öffentlichen und privaten sozialen Dienste sowie der Sozialen Arbeit als Profession und Disziplin. Beiträge über Subsidiarität, Integration, Lebensqualität, Staatlichkeit und Zivilgesellschaft, Effizienz- und Wirkungsorientierung, Risikominimierung, Prävention, soziale Ungleichheit, Eigenverantwortung und Selbstbestimmung schaffen einen Überblick über aktuelle soziale Problemlagen in der Schweiz und darauf zielende Konzepte. Das Handbuch wurde für die 2. Auflage überarbeitet und ergänzt. Es ist ein unentbehrliches Nachschlagewerk für alle, die sich mit dem Sozialwesen auseinandersetzen: Fachleute aus dem sozialen Bereich, Politikerinnen und Politiker, Studierende, Medienschaffende und weitere interessierte Personen.

Job-shadowing: Swiss health librarians observing experienced search specialists and information skills trainers in London

Abstract As librarians of the Social & Preventive Medicine Library in Bern, we help researchers perform systematic literature searches and teach students to use medical databases. We developed our skills mainly “on the job”, and we wondered how other health librarians in Europe were trained to become experts in searching. We had a great opportunity to “job shadow” specialists in this area of library service during a 5-day-internship at the Royal Free Hospital Medical Library in London, Great Britain.

Handrub Consumption Mirrors Hand Hygiene Compliance

We assessed handrub consumption as a surrogate marker for hand hygiene compliance from 2007 to 2014. Handrub consumption varied substantially between departments but correlated in a mixed effects regression model with the number of patient-days and the observed hand hygiene compliance. Handrub consumption may supplement traditional hand hygiene observations. Infect. Control Hosp. Epidemiol. 2016;1-4.

Taking Transgenic Plants with a Pinch of Salt

Making plants resistant to salty environments would be a boon for developing countries where poor land management has rendered large areas of arable land unfit for crop production. In a Perspective, Frommer and colleagues discuss how genetic engineering can be used to confer salt tolerance on plants ( see Apse et al.) and explore the implications of this feat for improving crop production in developing countries.

Rhesus factors and ammonium: a function in efflux?

Completion of fungal, plant and human genomes paved the way to the identification of erythrocytic rhesus proteins and their kidney homologs as ammonium transporters. Ammonium is the preferred nitrogen source of bacteria and fungi, and plants acquire nitrogen from the soil in the form of ammonium [1]. In animals and humans, assimilated forms of nitrogen - amino acids - are much preferred for nutrition, and, in the case of ammonotelic animals, ammonium is used for the excretion of nitrogen instead. In the human kidney, ammonium is produced, reabsorbed and excreted as a means to maintain pH balance and to get rid of surplus inorganic nitrogen. Whether ammonium transport also has a role in the pH regulation of other organs is not known and the molecular mechanisms were not, up to now, understood.

A New Family of High-Affinity Transporters for Adenine, Cytosine, and Purine Derivatives in Arabidopsis

In many organisms, including plants, nucleic acid bases and derivatives such as caffeine are transported across the plasma membrane. Cytokinins, important hormones structurally related to adenine, are produced mainly in root apices, from where they are translocated to shoots to control a multitude of physiological processes. Complementation of a yeast mutant deficient in adenine uptake (fcy2) with an Arabidopsis cDNA expression library enabled the identification of a gene, AtPUP1 (for Arabidopsis thaliana purine permease1), belonging to a large gene family (AtPUP1 to AtPUP15) encoding a new class of small, integral membrane proteins. AtPUP1 transports adenine and cytosine with high affinity. Uptake is energy dependent, occurs against a concentration gradient, and is sensitive to protonophores, potentially indicating secondary active transport. Competition studies show that purine derivatives (e.g., hypoxanthine), phytohormones (e.g., zeatin and kinetin), and alkaloids (e.g., caffeine) are potent inhibitors of adenine and cytosine uptake. Inhibition by cytokinins is competitive (competitive inhibition constant Ki = 20 to 35 μM), indicating that cytokinins are transported by this system. AtPUP1 is expressed in all organs except roots, indicating that the gene encodes an uptake system for root-derived nucleic acid base derivatives in shoots or that it exports nucleic acid base analogs from shoots by way of the phloem. The other family members may have different affinities for nucleic acid bases, perhaps functioning as transporters for nucleosides, nucleotides, and their derivatives.

Hypersensitivity of an Arabidopsis Sugar Signaling Mutant toward Exogenous Proline Application

In transgenic Arabidopsis a patatin class I promoter from potato is regulated by sugars and proline (Pro), thus integrating signals derived from carbon and nitrogen metabolism. In both cases a signaling cascade involving protein phosphatases is involved in induction. Other endogenous genes are also regulated by both Pro and carbohydrates. Chalcone synthase (CHS) gene expression is induced by both, whereas the Pro biosynthetic Δ1-pyrroline-5-carboxylate synthetase (P5CS) is induced by high Suc concentrations but repressed by Pro, and Pro dehydrogenase (ProDH) is inversely regulated. The mutantrsr1-1, impaired in sugar dependent induction of the patatin promoter, is hypersensitive to low levels of external Pro and develops autofluorescence and necroses. Toxicity of Pro can be ameliorated by salt stress and exogenously supplied metabolizable carbohydrates. The rsr1-1 mutant shows a reduced response regarding sugar induction of CHS andP5CS expression. ProDH expression is de-repressed in the mutant but still down-regulated by sugar. Pro toxicity seems to be mediated by the degradation intermediate Δ1-pyrroline-5-carboxylate. Induction of the patatin promoter by carbohydrates and Pro, together with the Pro hypersensitivity of the mutant rsr1-1, demonstrate a new link between carbon/nitrogen and stress responses.

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Theodor Lessing

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Theodor Lessing

Ludwig Jakobowski : einige Gedenkworte

Theodor Lessing

"Untergang der Erde am Geist"

Theodor Lessing