Career-Success Scale – A new instrument to assess young physicians' academic career steps

Background: Within the framework of a prospective cohort study of Swiss medical school graduates, a Career-Success Scale (CSS) was constructed in a sample of young physicians choosing different career paths in medicine. Furthermore the influence of personality factors, the participants' personal situation, and career related factors on their career success was investigated. Methods: 406 residents were assessed in terms of career aspired to, and their career progress. The Career-Success Scale, consisting of 7 items, was developed and validated, addressing objective criteria of academic career advancement. The influence of gender and career aspiration was investigated by a two-factorial analysis of variance, the relationships between personality factors, personal situation, career related factors and the Career-Success Scale by a multivariate linear regression analysis. Results: The unidimensional Career-Success Scale has an internal consistency of 0.76. It is significantly correlated at the bivariate level with gender, instrumentality, and all career related factors, particularly with academic career and received mentoring. In multiple regression, only gender, academic career, surgery as chosen specialty, and received mentoring are significant predictors. The highest values were observed in participants aspiring to an academic career, followed by those pursuing a hospital career and those wanting to run a private practice. Independent of the career aspired to, female residents have lower scores than their male colleagues. Conclusion: The Career-Success Scale proved to be a short, reliable and valid instrument to measure career achievements. As mentoring is an independent predictor of career success, mentoring programs could be an important instrument to specifically enhance careers of female physicians in academia

Swiss residents' arguments for and against a career in medicine

BACKGROUND: In some Western countries, the medical profession is continuously losing prestige, doctors are claiming of high demands, low rewards, and difficult structural working conditions. This study aimed to investigate the arguments given by Swiss residents for and against a career in medicine. METHODS: As part of a prospective cohort study of Swiss medical school graduates on career development, 567 fourth-year residents were asked to answer the free-response item of what arguments there still were in favour of or against a career in medicine. They also indicated whether they would choose the medical profession all over again (yes/no). The statements were transcribed, content categories inductively formulated, and their descriptions written down in a code manual. Arguments were encoded according to the code manual and assigned to eight content categories (Mayring's content analysis). Frequency distributions were given for categories and tested with Chi(2)-tests for differences in gender, speciality fields, and whether or not the respondent would again choose a career in medicine. RESULTS: The 567 participants made 1,640 statements in favour of and 1,703 statements against a career in medicine. The content analysis of the residents' answers yielded eight categories with arguments both for and against a career in medicine. Of all "statements for" responses, 70% fell into the two top-ranking categories of Personal experiences in day-to-day working life (41.2%) and Interpersonal experiences in professional relationships (28.8%). The top-ranking category of the "statements against" arguments was General work-related structural conditions (32%), followed by Social prestige and health-policy aspects (21%). Main arguments in favour of a career in medicine were interdisciplinary challenge, combination of basic sciences and interpersonal concerns, helping suffering people, guarantee of a secure job; arguments against comprised high workload, time pressure, emotional stress, poorly structured continuing education, increasing bureaucracy, work-life imbalance, low income, and decreasing social prestige. The statements revealed few differences depending on gender, medical field, and attitude towards choosing the medical profession again; one out of five young doctors would not do so. CONCLUSION: Residents' chief complaint is deteriorating structural working conditions, including unfavourable work-life balance. Making medicine an attractive profession again will require sustainable changes in health-policy framework and social reward

An “Escape Clock” for Estimating the Turnover of SIV DNA in Resting CD4+ T Cells

Persistence of HIV DNA presents a major barrier to the complete control of HIV infection under current therapies. Most studies suggest that cells with latently integrated HIV decay very slowly under therapy. However, it is much more difficult to study the turnover and persistence of HIV DNA during active infection. We have developed an “escape clock” approach for measuring the turnover of HIV DNA in resting CD4+ T cells. This approach studies the replacement of wild-type (WT) SIV DNA present in early infection by CTL escape mutant (EM) strains during later infection. Using a strain-specific real time PCR assay, we quantified the relative amounts of WT and EM strains in plasma SIV RNA and cellular SIV DNA. Thus we can track the formation and turnover of SIV DNA in sorted resting CD4+ T cells. We studied serial plasma and PBMC samples from 20 SIV-infected Mane-A*10 positive pigtail macaques that have a signature Gag CTL escape mutation. In animals with low viral load, WT virus laid down early in infection is extremely stable, and the decay of this WT species is very slow, consistent with findings in subjects on anti-retroviral medications. However, during active, high level infection, most SIV DNA in resting cells was turning over rapidly, suggesting a large pool of short-lived DNA produced by recent infection events. Our results suggest that, in order to reduce the formation of a stable population of SIV DNA, it will be important either to intervene very early or intervene during active replication

Scaling laws near the conformal window of many-flavor QCD

We derive universal scaling laws for physical observables such as the critical temperature, the chiral condensate, and the pion decay constant as a function of the flavor number near the conformal window of many-flavor QCD in the chiral limit. We argue on general grounds that the associated critical exponents are all interrelated and can be determined from the critical exponent of the running gauge coupling at the Caswell-Banks-Zaks infrared fixed point. We illustrate our findings with the aid of nonperturbative functional Renormalization Group (RG) calculations and low-energy QCD models.Comment: 18 pages, 4 figures, references added and discussion expanded (matches JHEP version

Rapid Turnover of 2-LTR HIV-1 DNA during Early Stage of Highly Active Antiretroviral Therapy

BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART), the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS) levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART

HSV-1 employs UL56 to antagonize expression and function of cGAMP channels

DNA sensing is important for antiviral immunity. The DNA sensor cGAS synthesizes 2'3'-cyclic GMP-AMP (cGAMP), a second messenger that activates STING, which induces innate immunity. cGAMP not only activates STING in the cell where it is produced but cGAMP also transfers to other cells. Transporters, channels, and pores (including SLC19A1, SLC46A2, P2X7, ABCC1, and volume-regulated anion channels (VRACs)) release cGAMP into the extracellular space and/or import cGAMP. We report that infection with multiple human viruses depletes some of these cGAMP conduits. This includes herpes simplex virus 1 (HSV-1) that targets SLC46A2, P2X7, and the VRAC subunits LRRC8A and LRRC8C for degradation. The HSV-1 protein UL56 is necessary and sufficient for these effects that are mediated at least partially by proteasomal turnover. UL56 thereby inhibits cGAMP uptake via VRAC, SLC46A2, and P2X7. Taken together, HSV-1 antagonizes intercellular cGAMP transfer. We propose that this limits innate immunity by reducing cell-to-cell communication via the immunotransmitter cGAMP

Biodegradative mechanism of the brown rot basidiomycete Gloeophyllum trabeum: evidence for an extracellular hydroquinone-driven fenton reaction

AbstractWe have identified key components of the extracellular oxidative system that the brown rot fungus Gloeophyllum trabeum uses to degrade a recalcitrant polymer, polyethylene glycol, via hydrogen abstraction reactions. G. trabeum produced an extracellular metabolite, 2,5-dimethoxy-1,4-benzoquinone, and reduced it to 2,5-dimethoxyhydroquinone. In the presence of 2,5-dimethoxy-1,4-benzoquinone, the fungus also reduced extracellular Fe3+ to Fe2+ and produced extracellular H2O2. Fe3+ reduction and H2O2 formation both resulted from a direct, non-enzymatic reaction between 2,5-dimethoxyhydroquinone and Fe3+. polyethylene glycol depolymerization by G. trabeum required both 2,5-dimethoxy-1,4-benzoquinone and Fe3+ and was completely inhibited by catalase. These results provide evidence that G. trabeum uses a hydroquinone-driven Fenton reaction to cleave polyethylene glycol. We propose that similar reactions account for the ability of G. trabeum to attack lignocellulose

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact