Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation

The granulocyte colony-stimulating factor receptor (G-CSF-R) transduces signals important for the proliferation and maturation of myeloid progenitor cells. To identify functionally important regions in the cytoplasmic domain of the G-CSF-R, we compared the actions of the wild-type receptor, two mutants, and a natural splice variant in transfectants of the mouse pro-B cell line BAF3 and two myeloid cell lines, 32D and L-GM. A region of 55 amino acids adjacent to the transmembrane domain was found to be sufficient for generating a growth signal. The immediate downstream sequence of 30 amino acids substantially enhanced the growth signaling in the three cell lines. In contrast, the carboxy-terminal part of 98 amino acids strongly inhibited growth signaling in the two myeloid cell lines but not in BAF3 cells. Truncation of this region lead to an inability of the G-CSF-R to transduce maturation signals in L-GM cells. An alternative carboxy tail present in a splice variant of the G-CSF-R also inhibited growth signaling, notably in both the myeloid cells and BAF3 cells, but appeared not to be involved in maturation

Investigating the prevalence of problematic substance use and mental disorders in a large sample of prisoners with mental illness: network analysis

Background The relationship between psychopathology and criminal offending has been the subject of many studies. Co-occurring substance use seems to increase the risk of offending in those with mental illness. Aims To present data on the prevalence of mental disorders and demographics of prisoners with mental illness, and investigate associations between diagnoses and substance use from a network perspective. Method Data used in this study are part of a cohort study within the four penitentiary psychiatric centres in The Netherlands. It includes data of 4956 incarcerated male patients. Prevalence rates of mental disorders and demographic variables were compared between individuals with and without problematic substance use. A network of diagnoses, including three categories of substance use, was constructed with regression coefficients. Results Most patients showed prior problematic substance use (72.2%) in more than one category of substances (58.7%). Problematic substance use was associated with diagnoses of schizophrenia spectrum disorders (χ2(1) = 37.52, P < 0.001, V = 0.09) and cluster B personality disorders (χ2(1) = 56.39, P < 0.001, V = 0.11). Three major findings of the network are discussed in detail: the role of antisocial personality disorder, impulsivity and psychotic disorders in combination with problematic substance use. Conclusions Problematic substance use is highly prevalent among prisoners with mental illness, and should always be taken into account in research on this topic. Treatment should target substance use to reduce the risk of recidivism. Further differentiation in categories of substances is needed for the development of risk profiles

Improving Quinolone Use in Hospitals by Using a Bundle of Interventions in an Interrupted Time Series Analysis

The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P < 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions

The choice for EU theorists: Establishing a common framework for analysis

European Union (EU) studies have entered a highly contentious and, arguably, creative phase. A range of theoretical perspectives, seemingly quite highly differentiated from one another, now compete for influence and lsquospacersquo. However, the questions remain: is EU studies developing theories which are truly competing theories? Or is it developing theories that do not compete so much as they aim to explain distinctly different pieces of the EU puzzle? This paper responds directly to these two questions, while reviewing recent literature on EU governance. It argues, first, that we lack theories of EU governance that are true rivals; and, second, that leading models explain different outcomes at different levels in a multi-level system of governance. The result is somewhat phoney debates between compatible theories masquerading as rivals, and between lsquocomparative politicsrsquo and lsquointernational relationsrsquo approaches. Above all, perhaps, we find middle range theories posing as general or lsquometa-theoriesrsquo. In the absence of a plausible general theory of EU governance, theorists must choose precisely which type of outcome theywish to explain

Orgelcultuur in een Deltagebied. Vijf Casestudies

ORGAN CULTURE IN A DELTA AREA contains five casestudies on organhistorical subjects. The first study Museum organs under the care of the government has been written as a contribution to a scientific discussion whether or not the famous 1479 Peter Gerritszorgan should be restored to a playable condition again after more than a century of museum conservation. The contribution focusses on the conservation history of the organs from the Amsterdam Rijksmuseum collection, among others based on the archives of the ministry of Education, Culture and Sciences. Among five instruments, only for the Peter Gerritszorgan the conservation of the complete instrument seems to have been intended after purchase in 1885. The second study A great work is an extended written result of a lecture during conference in Stockholm, 2003, on the Orchestrion that was built for the organ virtuoso and theorist Abbé Georg Joseph Vogler (1749-1814) by the Rotterdam organ builder Johannes Pieter Künckel (1750-1815). Since very few primary sources on this innovative transportable organ have survived, the description has mainly been derived from contemporary periodicals and a specification available in the Bayerische Staatsbibliothek. The third and fourth studies OF GOLDEN AND UNNECESSARY ORGANS and They did not seem to be aware of the jewel they possess are classic historic overviews of the organ history of the city of Dordrecht and the Rijnmond region. As Albert Schweitzer noticed in 1928, people of Rotterdam were unaware of the value of the organ of the Great or St. Laurens church. The typically Dutch underestimation of the meaning of proper cultural heritage and the tendency of expecting the best from far away gave reason to the idea that establishing a ‘School’ of organ builders hardly seems to have existed in the Rijnmond region. This seems especially to be applicable to the career of the Rotterdam organ builders Willem Hendrik Kam (1806-1863) and Hendrik van der Meulen (1810-1852). Their biographies are provided in the fifth study Accused of Mediocrity. According to independent contemporary experts as well as to more recent insights, their surviving instruments rank them among the most important Dutch organ builders of the 19th century. Yet, their career was firmly injured by the preoccupation of the Rotterdam church wardens who were wrongly informed of Kam and Van der Meulen’s so-called mediocrity. An anonymous newspaper discussion from their circle on the 1845 Bätz & Co. renovation of the Rotterdam Laurensorgan was not appreciated by the consultant involved. However, their surviving instruments at e.g. Zierikzee (1848), Nieuw-Lekkerland (1853), Ouderkerk aan den IJssel (1854) and Dordrecht (1859) all testify of their internationally orientated scholarly approach of organ buildin

'Weidegang staat op de agenda bij veehouders'

Het project Koe & Wij nadert zijn einde. Weidegang of opstallen, de veehouders denken weer bewust na over de wijze waarop ze hun melkvee willen houden, meent projectleider Bert Philipsen. Na twee jaar Koe & Wij maakt hij de balans op. “Wij willen de veehouders bewust laten nadenken over de overwegingen bij keuze voor weiden of opstallen”, vertelt Philipse