The extensive age gradient of the Carina dwarf galaxy

The evolution of small systems such as dwarf spheroidal galaxies (dSph) is likely to have been a balance between external environmental effects and internal processes within their own relatively shallow potential wells. Assessing how strong such environmental interactions may have been is therefore an important element in understanding the baryonic evolution of dSphs and their derived dark matter distribution. Here we present results from a wide-area CTIO/MOSAIC II photometric survey of the Carina dSph, reaching down to about two magnitudes below the oldest main sequence turn-off (MSTO). This data-set enables us to trace the structure of Carina in detail out to very large distances from its center, and as a function of stellar age. We observe the presence of an extended structure made up primarily of ancient MSTO stars, at distances between 25arcmin-60arcmin from Carina's center, confirming results in the literature that Carina extends well beyond its nominal tidal radius. The large number statistics of our survey reveals features such as isophote twists and tails that had gone undetected in other previous shallower surveys. This is the first time that such unambiguous signs of tidal disruption have been found in a Milky Way "classical" dwarf other than Sagittarius. We also demonstrate the presence of a negative age gradient in Carina directly from its MSTOs, and trace it out to very large distances from the galaxy center. The signs of interaction with the Milky Way make it unclear whether the age gradient was already in place before Carina underwent tidal disruption.Comment: Accepted for publication in The Astrophysical Journal Letter

Happiness at work: a phenomenological study of the experiences of hospitality industry employees

Though happiness might be an interesting factor to consider in the discussion on retaining employees, only a limited number of studies on  happiness of hospitality employees has been done. This master’s thesis study, rooted in the tradition of the interpretative phenomenological analysis, unpacks the connection of work experiences and feelings of happiness of five hospitality employees aged between 20 and 30. In-depth interviews revealed that happiness is found in moments of external recognition of professional achievements, while contributing to the company’s performance or to guest experiences. We see that these moments reinforce a high-performance attitude that, however, could also create a form of addiction. We recommend integrating appreciative feedback of staff achievements on a regular base during operations. Furthermore, we suggest staff coaching with the aim to develop self-awareness and self-acknowledgement. Keywords: added value, external recognition, happiness, interpretative phenomenological analysis, transient leve

Perinatal fluoxetine treatment and dams’ early life stress history have opposite effects on aggressive behavior while having little impact on sexual behavior of male rat offspring

Funding Information: This work was supported by the NARSAD young investigator grant from the Brain and Behavior Research Foundation (Grant No. 25206) and by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie (Grant Agreement No. 660152).Peer reviewedPublisher PD

Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective

Abstract Background A screening programme for pregnant women has been in place since the 1950s in the Netherlands. In 2004 universal HIV screening according to opting out was implemented. Here, we describe the evaluation of the effectiveness of antenatal screening in the Netherlands for 2006-2008 for HIV, hepatitis B virus (HBV) and syphilis in preventing mother-to-child transmission, by using various data sources. Methods The results of antenatal screening (2006-2008) were compared with data from pregnant women and newborns from other data sources. Results Each year, around 185,000 pregnant women were screened for HIV, HBV and syphilis. Refusal rates for the screening tests were low, and were highest (0.2%) for HIV. The estimated annual prevalence of HIV among pregnant women was 0.05%. Prior to the introduction of screening, 5-10 children were born with HIV annually After the introduction of screening in 2004, only 4 children were born with HIV (an average of 1 per year). Two of these mothers had become pregnant prior to 2004; the third mother was HIV negative at screening and probably became infected after screening; the fourth mother's background was unknown. Congenital syphilis was diagnosed in fewer than 5 newborns annually and 5 children were infected with HBV. In 3 of these, the mothers were HBeAg positive (a marker for high infectivity). We estimated that 5-10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually as a result of screening. Conclusions The screening programme was effective in detecting HIV, HBV and syphilis in pregnant women and in preventing transmission to the child. Since the introduction of the HIV screening the number of children born with HIV has fallen dramatically. Previous publication [Translation from: 'Prenatale screening op hiv, hepatitis B en syphilis in Nederland effectief', published in 'The Dutch Journal of Medicine ' (NTVG, in Dutch)]</p

Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release

Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone–dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p = 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2–deficient serum. CpG-B increased levels of IL-1β, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1–dependent cytokine release

Inclusion of Horizontal Branch stars in the derivation of star formation histories of dwarf galaxies: the Carina dSph

We present a detailed analysis of the Horizontal Branch of the Carina Dwarf Spheroidal Galaxy by means of synthetic modelling techniques, taking consistently into account the star formation history and metallicity evolution as determined from main sequence and red giant branch spectroscopic observations. We found that a range of integrated red giant branch mass loss values of 0.1-0.14 M, increasing with metallicity, is able to reproduce the colour extension of the old Horizontal Branch. However, leaving the mass loss as the only free parameter is not enough to match the detailed morphology of Carina Horizontal Branch. We explored the role played by the star formation history on the discrepancies between synthetic and observed Horizontal Branches. We derived a toy bursty star formation history that reproduces the horizontal branch star counts, and also matches qualitatively the red giant and the turn off regions. This star formation history is made of a subset of age and [M/H] components of the star formation history based on turn off and red giants only, and entails four separate bursts of star formation of different strenghts, centred at 2, 5, 8.6 and 11.5 Gyr, with mean [M/H] decreasing from \sim -1.7 to \sim -2.2 for increasing ages, and a Gaussian spread of 0.1 dex. The comparison between the metallicity distribution function of our star formation history and the one measured from the infrared CaT feature using a CaT-[Fe/H] calibration shows a qualitative agreement, once taken into account the range of [Ca/Fe] abundances measured in a sample of Carina stars, that biases the derived [Fe/H] distribution toward too low values. In conclusion, we have shown how the information contained within the horizontal branch of Carina (and dwarf galaxies in general) can be extracted and interpreted to refine the star formation history derived from red giants and turn off stars only. Abridge

PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY

BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards

Transcriptional Profiling of Human Familial Longevity Indicates a Role for ASF1A and IL7R

The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. We first compared gene expression profiles from whole blood samples between 50 nonagenarians and 50 middle-aged controls, resulting in identification of 2,953 probes that associated with age. Next, we determined which of these probes associated with longevity by comparing the offspring of the nonagenarians (50 subjects) and the middle-aged controls. The expression of 360 probes was found to change differentially with age in members of the long-lived families. In a RT-qPCR replication experiment utilizing 312 controls, 332 offspring and 79 nonagenarians, we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters. In conclusion, an “aging-signature” formed of 21 genes was identified, of which reduced expression of ASF1A and IL7R marked familial longevity already in middle-age. This indicates that expression changes of genes involved in metabolism, epigenetic control and immune function occur as a function of age, and some of these, like ASF1A and IL7R, represent early features of familial longevity and healthy ageing

Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors:A Dutch LATER study

Background: Meningiomas are the most frequent brain tumours occurring after pediatric cranial radiotherapy (CrRT). Data on course of disease, to inform clinical management of meningiomas, are sparse. This study reports the clinical characteristics of histologically confirmed meningiomas in childhood cancer survivors (CCS) in the Netherlands.& nbsp; Methods: In total, 6015 CCS from the Dutch Long-Term Effects After Childhood Cancer (LATER) cohort were eligible, including 1551 with prior CrRT. These CCS were diagnosed with cancer ag