A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients

The Line Emission Region in III Zw 2: Kinematics and Variability

We have studied the Ly-al, Hbeta, Halpha and Mg II2798 line profiles of the Seyfert 1 galaxy III Zw 2. The shapes of these broad emission lines show evidence of a multicomponent origin and also features which may be identified as the peaks due to a rotating disk. We have proposed a two-component Broad Line Region (BLR) model consisting of an inner Keplerian relativistic disk and an outer structure surrounding the disk. The results of the fitting of the four Broad Emission Lines (BELs) here considered, are highly consistent in both the inner and outer component parameters. Adopting a mass of approx. 2 E8 sollar masses for the central object we found that the outer radius of the disk is approximately equal for the four considered lines (approx 0.01 pc). However, the inner radius of the disk is not the same: 0.0018 pc for Ly-alpha, 0.0027 pc for Mg II, and 0.0038 pc for the Balmer lines. This as well as the relatively broad component present in the blue wings of the narrow [OIII] lines indicate stratification in the emission-line region. Using long-term Hbeta observations (1972-1990, 1998) we found a flux variation of the BEL with respect to the [OIII] lines.Comment: ApJ, accepted, 22 pages, 10 figure

Conceptualizing vulnerability for health effects of the covid-19 pandemic and the associated measures in utrecht and zeist:A concept map

The COVID-19 pandemic and the associated measures have impacted the health of many. Not all population groups are equally vulnerable to such health effects, possibly increasing health inequalities. We performed a group concept mapping procedure to define a common, context-specific understanding of what makes people vulnerable to health effects of the pandemic and the measures. We organized a two-step, blended brainstorming session with locally involved community members, using the brainstorm focus prompt ‘What I think makes people vulnerable for the COVID-19 pandemic and the measures is … ’. We asked participants to generate as many statements as possible. Participants then individually structured (sorted and ranked) these statements. The structuring data was analysed using the groupwisdom™ software and then interpreted by the researchers to generate the concept map. Ninety-eight statements were generated by 19 participants. Sixteen participants completed both structuring tasks. The final concept map consisted of 12 clusters of vulnerability factors, indicating a broad conceptualization of vulnerability during the pandemic. It is being used as a basis for future research and local supportive interventions. Concept mapping is an effective method to arrive at a vulnerability assessment in a community in a short time and, moreover, a method that promotes community engagement

Governance of Offshore IT Outsourcing at Shell Global Functions IT-BAM Development and Application of a Governance Framework to Improve Outsourcing Relationships

The lack of effective IT governance is widely recognized as a key inhibitor to successful global IT outsourcing relationships. In this study we present the development and application of a governance framework to improve outsourcing relationships. The approach used to developing an IT governance framework includes a meta model and a customization process to fit the framework to the target organization. The IT governance framework consists of four different elements (1) organisational structures, (2) joint processes between in- and outsourcer, (3) responsibilities that link roles to processes and (4) a diverse set of control indicators to measure the success of the relationship. The IT governance framework is put in practice in Shell GFIT BAM, a part of Shell that concluded to have a lack of management control over at least one of their outsourcing relationships. In a workshop the governance framework was used to perform a gap analysis between the current and desired governance. Several gaps were identified in the way roles and responsibilities are assigned and joint processes are set-up. Moreover, this workshop also showed the usefulness and usability of the IT governance framework in structuring, providing input and managing stakeholders in the discussions around IT governance

Identification of Ambient Molecular Clouds Associated with Galactic Supernova Remnant IC443

The Galactic supernova remnant (SNR) IC443 is one of the most studied core-collapse SNRs for its interaction with molecular clouds. However, the ambient molecular clouds with which IC443 is interacting have not been thoroughly studied and remain poorly understood. Using Five College Radio Astronomy Observatory 14m telescope, we obtained fully sampled maps of ~ 1{\deg} \times 1{\deg} region toward IC443 in the 12CO J=1-0 and HCO+ J=1-0 lines. In addition to the previously known molecular clouds in the velocity range v_lsr = -6 to -1 km/s (-3 km/s clouds), our observations reveal two new ambient molecular cloud components: small (~ 1') bright clouds in v_lsr = -8 to -3 km/s (SCs), and diffuse clouds in v_lsr = +3 to +10 km/s (+5 km/s clouds). Our data also reveal the detailed kinematics of the shocked molecular gas in IC443, however the focus of this paper is the physical relationship between the shocked clumps and the ambient cloud components. We find strong evidence that the SCs are associated with the shocked clumps. This is supported by the positional coincidence of the SCs with shocked clumps and other tracers of shocks. Furthermore, the kinematic features of some shocked clumps suggest that these are the ablated material from the SCs upon the impact of the SNR shock. The SCs are interpreted as dense cores of parental molecular clouds that survived the destruction by the pre-supernova evolution of the progenitor star or its nearby stars. We propose that the expanding SNR shock is now impacting some of the remaining cores and the gas is being ablated and accelerated producing the shocked molecular gas. The morphology of the +5 km/s clouds suggests an association with IC443. On the other hand, the -3 km/s clouds show no evidence for interaction.Comment: Accepted for publication in ApJ. 15 pages (with emulateapj.cls), 17 figures, and 2 table

Precise Modeling of the Exoplanet Host Star and CoRoT Main Target HD 52265

This paper presents a detailed and precise study of the characteristics of the Exoplanet Host Star and CoRoT main target HD 52265, as derived from asteroseismic studies. The results are compared with previous estimates, with a comprehensive summary and discussion. The basic method is similar to that previously used by the Toulouse group for solar-type stars. Models are computed with various initial chemical compositions and the computed p-mode frequencies are compared with the observed ones. All models include atomic diffusion and the importance of radiative accelerations is discussed. Several tests are used, including the usual frequency combinations and the fits of the \'echelle diagrams. The possible surface effects are introduced and discussed. Automatic codes are also used to find the best model for this star (SEEK, AMP) and their results are compared with that obtained with the detailed method. We find precise results for the mass, radius and age of this star, as well as its effective temperature and luminosity. We also give an estimate of the initial helium abundance. These results are important for the characterization of the star-planet system.Comment: 9 pages, 6 figures, 7 tables, to be published in Astronomy and Astrophysic

Ensuring HLA-matched platelet support requires an ethnic diverse donor population

BACKGROUND: Patients refractory for platelet transfusions benefit from human leukocyte antigen (HLA)-matched platelet transfusions. Differences in ethnic background of patients and donors could hamper the availability of sufficient numbers of HLA-matched donors for all patients. We evaluated our HLA-matched donor program and explored the role of ethnic background of patients related to the number of available donors. METHODS: We performed a cohort study among consecutive patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. The number of available matched donors was determined per patient. Haplotypes were constructed from genotypes with computer software (PyPop). Based on haplotypes, HaploStats, an algorithm from the National Marrow Donor Program, was used to assess the most likely ethnic background for patients with 5 or fewer and 30 or more donors. RESULTS: HLA typing was available for 19,478 donors in September 2017. A total of 1206 patients received 12,350 HLA-matched transfusions. A median of 83 (interquartile range, 18-266) donors were available per patient. For 95 (10.3%) patients, 5 or fewer donors were available. These patients were more likely to have an African American background, whereas patients with 30 or more donors were more often from Caucasian origin, compared with Caucasian origin for patients with 30 donors. CONCLUSION: Adequate transfusion support could be guaranteed for most but not all refractory patients. More non-Caucasian donors are required to ensure the availability of HLA-matched donors for all patients in the Netherlands