Does an activity based remuneration system attract young doctors to general practice?

<p>Abstract</p> <p>Background</p> <p>The use of increasingly complex payment schemes in primary care may represent a barrier to recruiting general practitioners (GP). The existing Norwegian remuneration system is fully activity based - 2/3 fee-for-service and 1/3 capitation. Given that the system has been designed and revised in close collaborations with the medical association, it is likely to correspond - at least to some degree - with the preferences of <it>current </it>GPs (men in majority). The objective of this paper was to study which preferences that young doctors (women in majority), who are the <it>potential entrants </it>to general practice have for activity based vs. salary based payment systems.</p> <p>Methods</p> <p>In November-December 2010 all last year medical students and all interns in Norway (n = 1.562) were invited to participate in an online survey. The respondents were asked their opinion on systems of remuneration for GPs; inclination to work as a GP; risk attitude; income preferences; work pace tolerance. The data was analysed using one-way ANOVA and multinomial logistic regression analysis.</p> <p>Results</p> <p>A total of 831 (53%) responded. Nearly half the sample (47%) did not consider the remuneration system to be important for their inclination to work as GP; 36% considered the current system to make general practice <it>more </it>attractive, while 17% considered it to make general practice <it>less </it>attractive. Those who are attracted by the existing system were men and those who think high income is important, while those who are deterred by the system are risk averse and less happy with a high work pace. On the question of preferred remuneration system, half the sample preferred a mix of salary and activity based remuneration (the median respondent would prefer a 50/50 mix). Only 20% preferred a fully activity based system like the existing one. A salary system was preferred by women, and those less concerned with high income, while a fully activity based system was preferred by men, and those happy with a high work pace.</p> <p>Conclusions</p> <p>Given a concern about low recruitment to general practice in Norway, and the fact that an increasing share of medical students is women, we were interested in the extent to which the current Norwegian remuneration system correspond with the preferences of potential GPs. This study suggests that an existing remuneration mechanism has a selection effect on who would like to become a GP. Those most attracted are income motivated men. Those deterred are risk averse, and less happy with a high work pace. More research is needed on the extent to which experienced GPs differ along the questions we asked potential GPs, as well as studying the relative importance of other attributes than payment schemes.</p

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations

Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin

A very luminous magnetar-powered supernova associated with an ultra-long gamma-ray burst

A new class of ultra-long duration (>10,000 s) gamma-ray bursts has recently been suggested1,2,3. They may originate in the explosion of stars with much larger radii than normal long gamma-ray bursts3,4 or in the tidal disruptions of a star3. No clear supernova had yet been associated with an ultra-long gamma-ray burst. Here we report that a supernova (2011kl) was associated with the ultra-long duration burst 111209A, at z=0.677. This supernova is more than 3 times more luminous than type Ic supernovae associated with long gamma-ray bursts5,6,7, and its spectrum is distinctly different. The continuum slope resembles those of super-luminous supernovae8,9, but extends farther down into the rest-frame ultra-violet implying a low metal content. The light curve evolves much more rapidly than super-luminous supernovae. The combination of high luminosity and low metal-line opacity cannot be reconciled with typical type Ic supernovae, but can be reproduced by a model where extra energy is injected by a strongly magnetized neutron star (a magnetar), which has also been proposed as the explanation for super-luminous supernovae20,20a

The NADPH Oxidase Complexes in <em>Botrytis cinerea</em>: Evidence for a Close Association with the ER and the Tetraspanin Pls1

<div><p>NADPH oxidases (Nox) are major enzymatic systems that generate reactive-oxygen species (ROS) in multicellular eukaryotes. In several fungi they have been shown to be involved in sexual differentiation and pathogenicity. However, in contrast to the well characterized mammalian systems, basic information on the composition, recruitment, and localization of fungal Nox complexes and on the molecular mechanisms of their cellular effects are still lacking. Here we give a detailed analysis of components of the Nox complexes in the gray mold fungus <em>Botrytis cinerea.</em> It had previously been shown that the two catalytic transmembrane subunits BcNoxA and B are important for development of sclerotia and for full virulence, with BcNoxA being involved in spreading of lesions and BcNoxB in penetration; BcNoxR functions as a regulator of both subunits. Here we present evidence (using for the first time a functional GFP fusion able to complement the ΔbcnoxA mutant) that BcNoxA localizes mainly to the ER and at the plasma membrane; BcNoxB shows a similar localization pattern, while the regulator BcNoxR is found in vesicles throughout the hyphae and at the hyphal tip. To identify possible interaction partners, which could be involved in the localization or recruitment of the Nox complexes, we functionally characterized the tetraspanin Pls1, a transmembrane protein, which had been suggested to be a NoxB-interacting partner in the saprophyte <em>Podospora anserina</em>. Knock-out experiments and GFP fusions substantiate a link between BcNoxB and BcPls1 because both deletion mutants have overlapping phenotypes (especially a defect in penetration), and the proteins show a similar localization pattern (ER). However, in contrast to the corresponding protein in <em>P. anserina</em> BcPls1 is important for female fertility, but not for ascospore germination.</p> </div

Cellular localization of the protein BcPls1.

<p>Protein localization was determined by confocal laser scanning microscopy (CLSM) in germlings of the strain Δbcpls1:gfp-Pls1 expressing a <i>gfp-bcpls1</i> gene fusion. 10-µl droplets of a conidial suspension in GB5 medium (10⁵ conida/ml) were given on a glass slide and were allowed to germinate over night before microscopic analyses were performed. <b>A</b>: Overview of BcPls1 localization in a <i>Botrytis cinerea</i> germling. BcPls1 mainly localizes to the border of circular structures in germinating hyphae that seem to be coherent (middle row). Higher magnification showed that the protein also localizes to structures at the edge of the hyphal tip (top row). Fluorescence is clearly limited to the last segment of the germling. The septal pore shows no fluorescence (white arrow, bottom row). <b>B</b>: Germlings were treated with the endocytosis marker FM4-64 (red, top right panel) to stain intracellular membranes. BcPls1 localization is shown in green (top left panel). White arrows indicate co-localization of BcPls1 fluorescence and the FM4-64 stained plasma membrane (see overlay, bottom left panel). Yellow arrows indicate localization of BcPls1 in membrane structures that are not stained by FM4-64 (indicative for the nuclear envelope/endoplasmic reticulum). <b>C</b>: Germlings were treated with the dye Hoechst (blue, top right panel) to stain nuclei. BcPls1 localization is shown in green (top left panel). White arrows indicate Hoechst- stained nuclei that are surrounded by the intracellular membrane structures BcPls1 localizes to ((see overlay, bottom left panel). <b>D:</b> Germlings were treated with the dyes FM4-64 (red, second row)) and Hoechst (blue, third row), simultaneously. BcPls1 localization is shown in green (first row). In addition to the membrane structures seen before (nuclear envelope), white arrows indicate localization of BcPls1 to the interior space of round structures, whose membranes are stained by FM4-64 (indicative for vacuoles). Scale bars in all images = 3 µm.</p

Sexual crosses of the WT and Δbcpls1 mutant.

<p><b>A:</b> Sexual crosses between <i>B. cinerea</i> SAS405 microconidia (standard strain of the opposite mating type to B05.10) and sclerotia of the B05.10 WT, two independent Δbcpls1 transformants and the Δbcpls1:GFP-Pls1 complementation strain. Sclerotia of the Δbcpls1 deletion strain show no morphological differences during their development but are sterile. <b>B:</b> Sexual crosses between <i>B. cinerea</i> SAS405 sclerotia and microconidia of the B05.10 WT, the Δbcpls1 mutants and the Δbcpls1:GFP-Pls1 complementation strains. Microconidia of the Δbcpls1 deletion strain are fertile.</p

Cellular localization of BcNoxA, BcNoxB and BcNoxR.

<p>Protein localization was determined by epifluorescence microscopy in germlings of the strains WT:GFP-NoxA, WT:NoxB-GFP and WT:GFP-NoxR expressing <i>gfp-bcnoxA, bcnoxB-gfp</i> and <i>gfp-noxR</i> gene fusions, respectively. 10-µl droplets of a conidial suspension in GB5 medium (10⁵ conida/ml) were placed on a glass slide and allowed to germinate over night before microscopic analyses were performed. <b>A</b>: BcNoxA localized to intracellular membrane structures and at times also to the plasma membrane. Staining with the ER-Tracker™ Blue-White DPX and a respective overlay show that the intracellular structures are partly consistent with the ER (from left to right: GFP-NoxA, ER-tracker, overlay, white light). <b>B</b>: BcNoxB localized to similar intracellular membrane structures and to the plasma membrane as visible for BcNoxA. Staining with the ER-Tracker™ Blue-White DPX and a respective overlay show that the intracellular structures visual are similar to ER structures (from left to right: NoxB-GFP, ER-tracker, overlay, white light). <b>C</b>: BcNoxR accumulated in cellular granules, which were distributed irregularly throughout the hyphae (left) and at the hyphal tip, where it seemed to determine the point of outgrowth (right, see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055879#pone.0055879.s009" target="_blank">movie S2</a>). Scale bars = 10 µm.</p

<i>In planta</i> penetration assay on bean leaves.

<p>Scanning electron microscopy (SEM) images of germinating conidia of the <i>B. cinerea</i> WT, Δbcpls1, ΔbcnoxA, ΔbcnoxB, ΔbcnoxAB and ΔbcnoxR were taken on the surface of bean leaves. Detached bean leaves were inoculated with conidial suspensions (2×10⁶ spores/ml) and 18 h after the infection samples were prepared for SEM by glutharaldehyde fixation, osmification, ethanol series, critical point drying and gold sputtering. Arrowheads indicate appressoria-like structures. Scale bars = 10 µm.</p

Complementation analyses of ΔbcnoxA and bcnoxR with <i>gfp</i>-constructs.

<p>Strains ΔbcnoxA:GFP-NoxA and ΔbcnoxR:GFP-NoxR expressing <i>gfp-noxA</i> and <i>gfp-noxR</i> gene fusions were tested for their phenotypical characteristics. The strains WT, ΔbcnoxA and ΔbcnoxR served as a control. The GFP-fusion constructs did complement the deletion phenotypes of ΔbcnoxA and ΔbcnoxR <b>A</b>: The ability to form sclerotia after 2 weeks incubation in darkness on CM media at 18°C is restored. <b>B</b>: The pathogenicity defect of the mutants is reinstated. Primary leaves of 10 day old French bean plants were inoculated with 7 µl droplets of conidial suspensions (2×10⁴ spores/ml in Gamborgs B5+2% glucose). Progression of infections was documented 3, 4 and 6 days after the infection (dpi).</p