sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of early pre-eclampsia in Spain)

Objective: A high ratio of soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to placental growth factor (PlGF) has been linked to pre‐eclampsia (PE). We evaluated the sFlt‐1/PlGF ratio as a predictive marker for early‐onset PE in women at risk of PE. Methods: This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt‐1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early‐onset PE (< 34 + 0 weeks). Serum sFlt‐1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model. Results: A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt‐1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1–9.3), 4.0 (IQR, 2.6–6.3) and 3.3 (IQR, 2.0–5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5–43.7), 18.4 (IQR, 8.2–57.9) and 51.9 (IQR, 11.5–145.6) for women with early‐onset PE; and 6.7 (IQR, 4.6–9.9), 4.7 (IQR, 2.8–7.2) and 6.0 (IQR, 3.8–10.5) for women with late‐onset PE. Compared with early‐onset PE, the sFlt‐1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late‐onset PE (P < 0.001 at each timepoint). A prediction model for early‐onset PE was developed, which included the sFlt‐1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver–operating characteristics curves of 0.86 (95% CI, 0.77–0.95), 0.91 (95% CI, 0.85–0.97) and 0.93 (95% CI, 0.86–0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt‐1/PlGF ratio alone or uterine artery mean pulsatility index. Conclusions: The sFlt‐1/PlGF ratio can improve prediction of early‐onset PE for women at risk of this condition

A Search for Dark Matter Annihilation with the Whipple 10m Telescope

We present observations of the dwarf galaxies Draco and Ursa Minor, the local group galaxies M32 and M33, and the globular cluster M15 conducted with the Whipple 10m gamma-ray telescope to search for the gamma-ray signature of self-annihilating weakly interacting massive particles (WIMPs) which may constitute astrophysical dark matter (DM). We review the motivations for selecting these sources based on their unique astrophysical environments and report the results of the data analysis which produced upper limits on excess rate of gamma rays for each source. We consider models for the DM distribution in each source based on the available observational constraints and discuss possible scenarios for the enhancement of the gamma-ray luminosity. Limits on the thermally averaged product of the total self-annihilation cross section and velocity of the WIMP, , are derived using conservative estimates for the magnitude of the astrophysical contribution to the gamma-ray flux. Although these limits do not constrain predictions from the currently favored theoretical models of supersymmetry (SUSY), future observations with VERITAS will probe a larger region of the WIMP parameter phase space, and WIMP particle mass (m_\chi).Comment: 33 pages, 12 figures, accepted for publication in the Astrophysical Journa

Multiwavelength Observations of the Gamma-Ray Blazar PKS 0528+134 in Quiescence

We present multiwavelength observations of the ultraluminous blazar-type radio loud quasar PKS 0528+134 in quiescence during the period July to December 2009. Significant flux variability on a time scale of several hours was found in the optical regime, accompanied by a weak trend of spectral softening with increasing flux. We suggest that this might be the signature of a contribution from the accretion disk at the blue end of the optical spectrum. The optical flux is weakly polarized with rapid variations of the degree and direction of polarization, while the polarization of the 43 GHz radio core remains steady. Optical spectropolarimetry suggests a trend of increasing degree of polarization with increasing wavelength, providing additional evidence for an accretion disc contribution towards the blue end of the optical spectrum. We constructed four SEDs indicating that even in the quiescent state, the bolometric luminosity of PKS 0528+134 is dominated by its gamma-ray emission. A leptonic single-zone jet model produced acceptable fits to the SEDs with contributions to the high-energy emission from synchrotron self-Compton radiation and Comptonization of direct accretion disk emission. Fit parameters close to equipartition were obtained. The moderate variability on long time scales implies the existence of on-going particle acceleration, while the observed optical polarization variability seems to point towards a turbulent acceleration process. Turbulent particle acceleration at stationary features along the jet therefore appears to be a viable possibility for the quiescent state of PKS 0528+134.Comment: Accepted for Publication in The Astrophysical Journal. - Acknowledgement adde

Accuracy of a method based on atomic absorption spectrometry to determine inorganic arsenic in food: outcome of the collaborative trial IMEP-41

A collaborative trial was conducted to determine the performance characteristics of an analytical method for the quantification of inorganic arsenic (iAs) in food. The method is based on (i) solubilisation of the protein matrix with concentrated hydrochloric acid to denature proteins and allow the release of all arsenic species into solution, and (ii) subsequent extraction of the inorganic arsenic present in the acid medium using chloroform followed by back-extraction to acidic medium. The final detection and quantification is done by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). The seven test items used in this exercise were reference materials covering a broad range of matrices: mussels, cabbage, seaweed (hijiki), fish protein, rice, wheat, mushrooms, with concentrations ranging from 0.074 to 7.55 mg kg(-1). The relative standard deviation for repeatability (RSDr) ranged from 4.1 to 10.3%, while the relative standard deviation for reproducibility (RSDR) ranged from 6.1 to 22.8%. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

The TeV spectrum of H1426+428

The BL Lac object H1426+428 was recently detected as a high energy gamma-ray source by the VERITAS collaboration (Horan et al. 2002). We have reanalyzed the 2001 portion of the data used in the detection in order to examine the spectrum of H1426+428 above 250 GeV. We find that the time-averaged spectrum agrees with a power law of the shape dF/dE = 10^(-7.31 +- 0.15(stat) +- 0.16(syst)) x E^(-3.50 +- 0.35(stat) +- 0.05(syst)) m^(-2)s^(-1)TeV^(-1) The statistical evidence from our data for emission above 2.5 TeV is 2.6 sigma. With 95% c.l., the integral flux of H1426+428 above 2.5 TeV is larger than 3% of the corresponding flux from the Crab Nebula. The spectrum is consistent with the (non-contemporaneous) measurement by Aharonian et al. (2002) both in shape and in normalization. Below 800 GeV, the data clearly favours a spectrum steeper than that of any other TeV Blazar observed so far indicating a difference in the processes involved either at the source or in the intervening space.Comment: LaTeX, 8 pages, 4 figures, accepted for publication in Ap

Detection of the BL Lac Object H1426+428 at TeV Gamma Ray Energies

A very high energy (VHE) gamma-ray signal has been detected at the 5.4 sigma level from H1426+428, an x-ray selected BL Lacertae object at a redshift of 0.129. The object was monitored from 1995 - 1998 with the Whipple 10m imaging atmospheric Cherenkov telescope as part of a general blazar survey; the results of these observations, although not statistically significant, were consistently positive. X-ray observations of H1426+428 during 1999 with the BeppoSAX instrument revealed that the peak of its synchrotron spectrum occurs at > 100 keV, leading to the prediction of observable TeV emission from this object. H1426+428 was monitored extensively at the Whipple Observatory during the 1999, 2000, and 2001 observing seasons. The strongest TeV signals were detected in 2000 and 2001. During 2001, an integral flux of 2.04 +/- 0.35 x10e-11 cm-2 s-1 above 280 GeV was recorded from H1426+428. The detection of H1426+428 supports the idea that, as also seen in Markarian 501 and 1ES2344+514, BL Lacertae objects with extremely high synchrotron peak frequencies produce gamma rays in the TeV range.Comment: 35 pages, 7 figures, accepted by ApJ Two upper limits in Table 3 (upper limits for 1995 and 1997) are different from the ApJ versio

IT-supported integrated care pathways for diabetes: A compilation and review of good practices

Introduction: Integrated Care Pathways (ICPs) are a method for the mutual decision-making and organization of care for a well-defined group of patients during a well-defined period. The aim of a care pathway is to enhance the quality of care by improving patient outcomes, promoting patient safety, increasing patient satisfaction, and optimizing the use of resources. To describe this concept, different names are used, e.g. care pathways and integrated care pathways. Modern information technologies (IT) can support ICPs by enabling patient empowerment, better management, and the monitoring of care provided by multidisciplinary teams. This study analyses ICPs across Europe, identifying commonalities and success factors to establish good practices for IT-supported ICPs in diabetes care. Methods: A mixed-method approach was applied, combining desk research on 24 projects from the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) with follow-up interviews of project participants, and a non-systematic literature review. We applied a Delphi technique to select process and outcome indicators, derived from different literature sources which were compiled and applied for the identification of successful good practices. Results: Desk research identified sixteen projects featuring IT-supported ICPs, mostly derived from the EIP on AHA, as good practices based on our criteria. Follow-up interviews were then conducted with representatives from 9 of the 16 projects to gather information not publicly available and understand how these projects were meeting the identified criteria. In parallel, the non-systematic literature review of 434 PubMed search results revealed a total of eight relevant projects. On the basis of the selected EIP on AHA project data and non-systematic literature review, no commonalities with regard to defined process or outcome indicators could be identified through our approach. Conversely, the research produced a heterogeneous picture in all aspects of the projects’ indicators. Data from desk research and follow-up interviews partly lacked information on outcome and performance, which limited the comparison between practices. Conclusion: Applying a comprehensive set of indicators in a multi-method approach to assess the projects included in this research study did not reveal any obvious commonalities which might serve as a blueprint for future IT-supported ICP projects. Instead, an unexpected high degree of heterogeneity was observed, that may reflect diverse local implementation requirements e.g. specificities of the local healthcare system, local regulations, or preexisting structures used for the project setup. Improving the definition of and reporting on project outcomes could help advance research on and implementation of effective integrated care solutions for chronic disease management across Europe

Search for High Energy Gamma Rays from an X-ray Selected Blazar Sample

Our understanding of blazars has been greatly increased in recent years by extensive multi-wavelength observations, particularly in the radio, X-ray and gamma-ray regions. Over the past decade the Whipple 10m telescope has contributed to this with the detection of 5 BL Lacertae objects at very high gamma-ray energies. The combination of multi-wavelength data has shown that blazars follow a well-defined sequence in terms of their broadband spectral properties. Together with providing constraints on emission models, this information has yielded a means by which potential sources of TeV emission may be identified and predictions made as to their possible gamma-ray flux. We have used the Whipple telescope to search for TeV gamma-ray emission from eight objects selected from a list of such candidates. No evidence has been found for VHE emission from the objects in our sample, and upper limits have been derived for the mean gamma-ray flux above 390GeV. These flux upper limits are compared with the model predictions and the implications of our results for future observations are discussed.Comment: 15 pages, 2 figures, Accepted for publication in Ap

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency