Psoralen and ultraviolet A light treatment directly affects phosphatidylinositol 3-kinase signal transduction by altering plasma membrane packing

Psoralen and ultraviolet A light (PUNTA) are used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma, and graft versus-host disease. DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery, they are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA. Such adducts increased lipid packing as measured by a blue shift of an environment-sensitive fluorescent probe in model liposomes. Furthermore, the interaction of these liposomes with lipid order-sensitive proteins like amphipathic lipid-packing sensor and a-synuclein was inhibited by PUVA. In platelets, PUVA caused poor membrane binding of Akt and Bruton's tyrosine kinase effectors following activation of the collagen glycoprotein VI and thrombin protease-activated receptor (PAR) 1. This resulted in defective Akt phosphorylation despite unaltered phosphatidylinositol 3,4,5-trisphosphate levels. Downstream integrin activation was furthermore affected similarly by PUVA following PAR1 (effective half-maximal concentration (EC), 8.4 +/- 1.1 versus 4.3 +/- 1.1 mu M) and glycoprotein VI (EC50, 1.61 +/- 0.85 versus 0.26 +/- 0.21 mu g/ml) but not PAR4 (EC50, 50 +/- 1 versus 58 +/- 1 mu m) signal transduction. Our findings were confirmed in T-cells ftom graft-versus-host disease patients treated with extracorporeal photopheresis, a form of systemic PUVA. In conclusion, PUVA increases the order of lipid phases by covalent modification of phospholipids, thereby inhibiting membrane recruitment of effector kinases

Evaluation of automated sample preparation, retention time locked GC-MS and automated data analysis for the metabolomic study of Arabidopsis species

One of the most critical parameters in GC-MS application to metabolimic studies is the sample preparation. Often a combination of oximation and silylation is used and this method is applicable to acids (e.g. fatty acids), sterols, amines, amino acids, sugars, etc. Automation of the derivatisation process enhances repeatability and the time between sample preparation and analysis can be kept short and constant. For analysis, retention time locked (RTL) gas chromatography/mass spectrometry was used. For data analysis, AMDIS deconvolution followed by 2 multivariate statistical approaches were used and compared. Arabidopsis thaliana, a popular model organism in plant biology and genetics, was used for testing. The data analysis software allowed the detection of several features that were up- or downregulated in the different species

A Radial Velocity Study of Composite-Spectra Hot Subdwarf Stars with the Hobby-Eberly Telescope

Many hot subdwarf stars show composite spectral energy distributions indicative of cool main sequence companions. Binary population synthesis (BPS) models demonstrate such systems can be formed via Roche lobe overflow or common envelope evolution but disagree on whether the resulting orbital periods will be long (years) or short (days). Few studies have been carried out to assess the orbital parameters of these spectroscopic composite binaries; current observations suggest the periods are long. To help address this problem, we selected fifteen moderately-bright (V~13) hot subdwarfs with F-K dwarf companions and monitored their radial velocities (RVs) from January 2005 to July 2008 using the bench-mounted Medium Resolution Spectrograph on the Hobby-Eberly Telescope (HET). Here we describe the details of our observing, reduction, and analysis techniques and present preliminary results for all targets. By combining the HET data with recent observations from the Mercator telescope, we are able to calculate precise orbital solutions for three systems using more than 6 years of observations. We also present an up-to-date period histogram for all known hot subdwarf binaries, which suggests those with F-K main sequence companions tend to have orbital periods on the order of several years. Such long periods challenge the predictions of conventional BPS models, although a larger sample is needed for a thorough assessment of the models' predictive success. Lastly, one of our targets has an eccentric orbit, implying some composite-spectrum systems might have formerly been hierarchical triple systems, in which the inner binary merged to create the hot subdwarf.Comment: Published in The Astrophysical Journal, Volume 758, Issue 1, article id. 58 (2012). References updated and Equation (5) corrected. 12 pages, 5 figures, 5 table

Cumulative incidence of child protection system contacts among a cohort of Western Australian Aboriginal children born 2000 to 2013

Background: Reducing the over-representation of Aboriginal children in the child protection system is a key target for the Australian government. Objective: We aimed to provide more recent evidence on the population-level cumulative incidence of contacts for Aboriginal children with child protective services (CPS) in Western Australia (WA). Participants and Setting: Linked administrative data was provided for WA CPS between 2000 and 2015 for 33,709 Aboriginal children born in WA between 2000 and 2013. Methods: Descriptive summaries and cumulative incidence estimates were used to examine changes in CPS contact trends over time and within sibling groups. Results: There was an increase in early-childhood contacts for children born more recently, with 7.6 % and 2.3 % of children born in 2000–2001 having a notification and placement in out-of-home care by age one, respectively, compared to 15.1 % and 4.3 % of children born in 2012–2013. Among sibling groups where at least one sibling had a CPS contact, approximately half of children had their first contacts on the same date as another sibling. For children born after one of their siblings had been placed in out-of-home care, 31.9 % had themselves been placed in out-of-home care by age one. Conclusions: Multiple children tend to be placed into out-of-home care when at least one sibling is, which is likely to have a significant impact on families affected. The additional risk of placement also carries over to children born after the first removal in a sibling group, highlighting the need for further support to prevent future removals

Health economic analysis of a cluster‐randomised trial (OptiBIRTH) designed to increase rates of vaginal birth after caesarean section

Der Artikel wurde innerhalb des EU-Projekts OptiBIRTH erstellt.This is the peer reviewed version of the following article: [Haunberger, S, Rüegger, C, Baumgartner, E. Experiences with a psychosocial screening instrument (S‐FIRST) to identify the psychosocial support needs of parents of children suffering from cancer. Psycho‐Oncology. 2019; 28: 1025‐ 1032.], which has been published in final form at https://doi.org/10.1002/pon.5045. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Objective: To perform a health economic analysis of an intervention designed to increase rates of vaginal birth after caesarean, compared with usual care. Design: Economic analysis alongside the cluster-randomised OptiBIRTH trial (Optimising childbirth by increasing vaginal birth after caesarean section (VBAC) through enhanced women-centred care). Setting: Fifteen maternity units in three European countries - Germany (five), Ireland (five), and Italy (five) - with relatively low VBAC rates. Population: Pregnant women with a history of one previous lower-segment caesarean section; sites were randomised (3:2) to intervention or control. Methods: A cost-utility analysis from both societal and health-services perspectives, using a decision tree. Main Outcome Measures: Costs and resource use per woman and infant were compared between the control and intervention group by country, from pregnancy recognition until 3 months postpartum. Based on the caesarean section rates, and maternal and neonatal morbidities and mortality, the incremental cost-utility ratios were calculated per country. Results: The mean difference in costs per quality-adjusted life years (QALYs) gained from a societal perspective between the intervention and the control group, using a probabilistic sensitivity analysis, was: €263 (95% CI €258-268) and 0.008 QALYs (95% CI 0.008-0.009 QALYs) for Germany, €456 (95% CI €448-464) and 0.052 QALYs (95% CI 0.051-0.053 QALYs) for Ireland, and €1174 (95% CI €1170-1178) and 0.006 QALYs (95% CI 0.005-0.007 QALYs) for Italy. The incremental cost-utility ratios were €33,741/QALY for Germany, €8785/QALY for Ireland, and €214,318/QALY for Italy, with a 51% probability of being cost-effective for Germany, 92% for Ireland, and 15% for Italy. Conclusion: The OptiBIRTH intervention was likely to be cost-effective in Ireland and Germany

Season Spotter: Using Citizen Science to Validate and Scale Plant Phenology from Near-Surface Remote Sensing

Abstract: The impact of a rapidly changing climate on the biosphere is an urgent area of research for mitigation policy and management. Plant phenology is a sensitive indicator of climate change and regulates the seasonality of carbon, water, and energy fluxes between the land surface and the climate system, making it an important tool for studying biosphere-atmosphere interactions. To monitor plant phenology at regional and continental scales, automated near-surface cameras are being increasingly used to supplement phenology data derived from satellite imagery and data from ground-based human observers. We used imagery from a network of phenology cameras in a citizen science project called Season Spotter to investigate whether information could be derived from these images beyond standard, color-based vegetation indices. We found that engaging citizen science volunteers resulted in useful science knowledge in three ways: first, volunteers were able to detect some, but not all, reproductive phenology events, connecting landscape-level measures with field-based measures. Second, volunteers successfully demarcated individual trees in landscape imagery, facilitating scaling of vegetation indices from organism to ecosystem. And third, volunteers’ data were used to validate phenology transition dates calculated from vegetation indices and to identify potential improvements to existing algorithms to enable better biological interpretation. As a result, the use of citizen science in combination with near-surface remote sensing of phenology can be used to link ground-based phenology observations to satellite sensor data for scaling and validation. Well-designed citizen science projects targeting improved data processing and validation of remote sensing imagery hold promise for providing the data needed to address grand challenges in environmental science and Earth observation.Organismic and Evolutionary Biolog

Tiger reefs: Self‐organized regular patterns in deep‐sea cold‐water coral reefs

Complexity theory predicts that self-organized, regularly patterned ecosystems store more biomass and are more resilient than spatially uniform systems. Self-organized ecosystems are well-known from the terrestrial realm, with “tiger bushes” being the archetypical example and mussel beds and tropical coral reefs the marine examples. We here identify regular spatial patterns in cold-water coral reefs (nicknamed “tiger reefs”) from video transects and argue that these are likely the result of self-organization. We used variograms and Lomb–Scargle analysis of seven annotated video transects to analyze spatial patterns in live coral and dead coral (i.e., skeletal remains) cover at the Logachev coral mound province (NE Atlantic Ocean) and found regular spatial patterns with length scales between 62 and 523 m in live and dead coral distribution along these transects that point to self-organization of cold-water coral reefs. Self-organization theory shows that self-organized ecosystems can withstand large environmental changes by adjusting their spatial configuration. We found indications that cold-water corals can similarly adjust their spatial configuration, possibly providing resilience in the face of climate change. Dead coral framework remains in the environment for extended periods of time, providing a template for spatial patterns that facilitates live coral recovery. The notion of regular spatial patterns in cold-water coral reefs is interesting for cold-water coral restoration, as transplantation will be more successful when it follows the patterns that are naturally present. This finding also underlines that anthropogenic effects such as ocean acidification and bottom trawling that destroy the dead coral template undermine cold-water coral resilience. Differences in the pattern periodicities of live and dead coral cover further present an interesting new angle to investigate past and present environmental conditions in cold-water coral reefs

Prospective Evaluation of Sleep Apnea as Manifestation of Heart Failure in Children

In adults with heart failure, central sleep apnea (CSA), often manifested as Cheyne–Stokes respiration, is common, and has been associated with adverse outcome. Heart failure in children is commonly caused by dilated cardiomyopathy (DCM). It is unknown whether children with heart failure secondary to DCM have CSA, and whether CSA is related to the severity of heart failure. In this prospective observational study, 37 patients (<18 year) with heart failure secondary to DCM were included. They underwent polysomnography, clinical and laboratory evaluation and echocardiographic assessment. After a median follow-up time of 2 years, eight patients underwent heart transplantation. CSA (apnea–hypopnea index [AHI] ≥1) was found in 19 % of the patients. AHI ranged from 1.2 to 4.5/h. The occurrence of CSA was not related to the severity of heart failure. Three older patients showed a breathing pattern mimicking Cheyne–Stokes respiration, two of whom required heart transplantation. CSA was found in 19 % of the children with heart failure secondary to DCM. No relation was found with the severity of heart failure. In a small subset of children with severe DCM, a pattern mimicking Cheyne–Stokes respiration was registered