2,791 research outputs found

    Snowmelt timing alters shallow but not deep soil moisture in the Sierra Nevada

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    Roughly one-third of the Earth's land surface is seasonally covered by snow. In many of these ecosystems, the spring snowpack is melting earlier due to climatic warming and atmospheric dust deposition, which could greatly modify soil water resources during the growing season. Though snowmelt timing is known to influence soil water availability during summer, there is little known about the depth of the effects and how long the effects persist. We therefore manipulated the timing of seasonal snowmelt in a high-elevation mixed-conifer forest in a Mediterranean climate during consecutive wet and dry years. The snow-all-gone (SAG) date was advanced by 6 days in the wet year and 3 days in the dry year using black sand to reduce the snow surface albedo. To maximize variation in snowmelt timing, we also postponed the SAG date by 8 days in the wet year and 16 days in the dry year using white fabric to shade the snowpack from solar radiation. We found that deeper soil water (30-60 cm) did not show a statistically significant response to snowmelt timing. Shallow soil water (0-30 cm), however, responded strongly to snowmelt timing. The drying effect of accelerated snowmelt lasted 2 months in the 0-15 cm depth and at least 4 months in the 15-30 cm depth. Therefore, the legacy of snowmelt timing on soil moisture can persist through dry periods, and continued earlier snowmelt due to climatic warming and windblown dust could reduce near-surface water storage and availability to plants and soil biota. Key Points The hydrological signal of snowmelt timing was strongest in shallow soil Effects of snowmelt timing on soil moisture lasted 2-4 months Advancing snowmelt timing by 2-3 weeks depleted shallow soil water by one third © 2014. American Geophysical Union. All Rights Reserved

    Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

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    Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

    Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: an observational study

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    Contains fulltext : 98009.pdf (publisher's version ) (Open Access)INTRODUCTION: Anemia is a frequently encountered problem during inflammation. Hepcidin is an interleukin-6 (IL-6)-induced key modulator of inflammation-associated anemia. Human sepsis is a prototypical inflammatory syndrome, often complicated by the development of anemia. However, the association between inflammation, hepcidin release and anemia has not been demonstrated in this group of patients. Therefore, we explored the association between hepcidin and sepsis-associated anemia. METHODS: 92 consecutive patients were enrolled after presentation on the emergency ward of a university hospital with sepsis, indicated by the presence of a proven or suspected infection and >/= 2 extended systemic inflammatory response syndrome (SIRS) criteria. Blood was drawn at day 1, 2 and 3 after admission for the measurement of IL-6 and hepcidin-25. IL-6 levels were correlated with hepcidin concentrations. Hemoglobin levels and data of blood transfusions during 14 days after hospitalisation were retrieved and the rate of hemoglobin decrease was correlated to hepcidin levels. RESULTS: 53 men and 39 women with a mean age of 53.3 +/- 1.8 yrs were included. Hepcidin levels were highest at admission (median[IQR]): 17.9[10.1 to 28.4]nmol/l and decreased to normal levels in most patients within 3 days (9.5[3.4 to 17.9]nmol/l). Hepcidin levels increased with the number of extended SIRS criteria (P = 0.0005). Highest IL-6 levels were measured at admission (125.0[46.3 to 330.0]pg/ml) and log-transformed IL-6 levels significantly correlated with hepcidin levels at admission (r = 0.28, P = 0.015), day 2 (r = 0.51, P < 0.0001) and day 3 (r = 0.46, P < 0.0001). Twelve patients received one or more blood transfusions during the first 2 weeks of admission, not related to active bleeding. These patients had borderline significant higher hepcidin level at admission compared to non-transfused patients (26.9[17.2 to 53.9] vs 17.9[9.9 to 28.8]nmol/l, P = 0.052). IL-6 concentrations did not differ between both groups. Correlation analyses showed significant associations between hepcidin levels on day 2 and 3 and the rate of decrease in hemoglobin (Spearman's r ranging from -0.32, P = 0.03 to -0.37, P = 0.016, respectively). CONCLUSIONS: These data suggest that hepcidin-25 may be an important modulator of anemia in septic patients with systemic inflammation

    Unscheduled return visits to a Dutch inner-city emergency department

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    © 2014, van der Linden et al.; licensee Springer. Background: Unscheduled return visits to the emergency department (ED) may reflect shortcomings in care. This study characterized ED return visits with respect to incidence, risk factors, reasons and post-ED disposition. We hypothesized that risk factors for unscheduled return and reasons for returning would differ from previous studies, due to differences in health care systems. Methods: All unscheduled return visits occurring within 1 week and related to the initial ED visit were selected. Multivariable logistic regression was conducted to determine independent factors associated with unscheduled return, using patient information available at the initial visit. Reasons for returning unscheduled were categorized into illness-, patient- or physician-related. Post-ED disposition was compared between patients with unscheduled return visits and the patients who did not return. Results: Five percent (n = 2,492) of total ED visits (n = 49,341) were unscheduled return visits. Patients with an urgent triage level, patients presenting during the night shift, with a wound or local infection, abdominal pain or urinary problems were more likely to return unscheduled. Reasons to revisit unscheduled were mostly illness-related (49%) or patient-related (41%). Admission rates for returning patients (16%) were the same as for the patients who did not return (17%). Conclusions: Apart from abdominal complaints, risk factors for unscheduled return differ from previous studies. Short-term follow-up at the outpatient clinic or general practitioner for patients with urgent triage levels and suffering from wounds or local infections, abdominal pain or urinary problem might prevent unscheduled return

    Self-referring patients at the emergency department: appropriateness of ED use and motives for self-referral

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    © 2014, van der Linden et al.; licensee Springer. Background: Nearly all Dutch citizens have a general practitioner (GP), acting as a gatekeeper to secondary care. Some patients bypass the GP and present to the emergency department (ED). To make best use of existing emergency care, Dutch health policy makers and insurance companies have proposed the integration of EDs and GP cooperatives (GPCs) into one facility. In this study, we examined ED use and assessed the characteristics of self-referrals and non-self-referrals, their need for hospital emergency care and self-referrals' motives for presenting at the ED. Methods: A descriptive cohort study was conducted in a Dutch level 1 trauma centre. Differences in patient characteristics, time of presentation and need for hospital emergency care were analysed using χ2 tests and t tests. A patient was considered to need hospital emergency care when he/she was admitted to the hospital, had an extremity fracture and/or when diagnostic tests were performed. Main determinants of self-referral were identified via logistic regression. Results: Of the 5,003 consecutive ED patients registering within the 5-week study period, 3,028 (60.5%) were self-referrals. Thirty-nine percent of the self-referrals had urgent acuity levels, as opposed to 65% of the non-self-referrals. Self-referrals more often suffered from injuries (49 vs. 20%). One third of the self-referrals presented during office hours. Of all self-referrals, 51% needed hospital emergency care. Younger age; non-urgent acuity level; chest pain, ear, nose or throat problems; and injuries were independent predictors for self-referral. Most cited motives for self-referring were ‘accessibility and convenience’ and perceived ‘medical necessity’. Conclusions: A substantial part of the self-referrals needed hospital emergency care. The 49% self-referrals who were eligible for GP care presented during out-of-hours as well as during office hours. This calls for an integrative approach to this health care problem

    The Multiscale Systems Immunology project: software for cell-based immunological simulation

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    <p>Abstract</p> <p>Background</p> <p>Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent based immune response simulation that incorporates realistic biophysics and intracellular dynamics, and which is sufficiently flexible to accurately model the multi-scale nature and complexity of the immune system, while maintaining the high performance critical to scientific computing.</p> <p>Results</p> <p>The Multiscale Systems Immunology (MSI) simulation framework is an object-oriented, modular simulation framework written in C++ and Python. The software implements a modular design that allows for flexible configuration of components and initialization of parameters, thus allowing simulations to be run that model processes occurring over different temporal and spatial scales.</p> <p>Conclusion</p> <p>MSI addresses the need for a flexible and high-performing agent based model of the immune system.</p

    Leishmania isoenzyme polymorphisms in Ecuador: Relationships with geographic distribution and clinical presentation

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    Background: Determinants of the clinical presentation of the leishmaniases are poorly understood but Leishmania species and strain differences are important. To examine the relationship between clinical presentation, species and isoenzyme polymorphisms, 56 Leishmania isolates from distinct presentations of American tegumentary leishmaniasis (ATL) from Ecuador were analyzed. Methods: Isolates were characterized by multilocus enzyme electrophoresis for polymorphisms of 11 isoenzymes. Patients were infected in four different ecologic regions: highland and lowland jungle of the Pacific coast, Amazonian lowlands and Andean highlands. Results: Six Leishmania species constituting 21 zymodemes were identified: L. (Viannia) panamensis (21 isolates, 7 zymodemes), L. (V.) guyanensis (7 isolates, 4 zymodemes), L. (V.) braziliensis (5 isolates, 3 zymodemes), L. (Leishmania) mexicana (11 isolates, 4 zymodemes), L. (L.) amazonensis (10 isolates, 2 zymodemes) and L. (L.) major (2 isolates, 1 zymodeme). L. panamensis was the species most frequently identified in the Pacific region and was associated with several clinical variants of cutaneous disease (CL); eight cases of leishmaniasis recidiva cutis (LRC) found in the Pacific highlands were associated with 3 zymodemes of this species. Mucocutaneous leishmaniasis found only in the Amazonian focus was associated with 3 zymodemes of L. braziliensis. The papular variant of CL, Uta, found in the Andean highlands was related predominantly with a single zymodeme of L. mexicana. Conclusion: Our data show a high degree of phenotypic variation within species, and some evidence for associations between specific variants of ATL (i.e. Uta and LRC) and specific Leishmania zymodemes. This study further defines the geographic distribution of Leishmania species and clinical variants of ATL in Ecuador

    Theory of Star Formation

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    We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

    Constraining Proton Lifetime in SO(10) with Stabilized Doublet-Triplet Splitting

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    We present a class of realistic unified models based on supersymmetric SO(10) wherein issues related to natural doublet-triplet (DT) splitting are fully resolved. Using a minimal set of low dimensional Higgs fields which includes a single adjoint, we show that the Dimopoulos--Wilzcek mechanism for DT splitting can be made stable in the presence of all higher order operators without having pseudo-Goldstone bosons and flat directions. The \mu term of order TeV is found to be naturally induced. A Z_2-assisted anomalous U(1)_A gauge symmetry plays a crucial role in achieving these results. The threshold corrections to alpha_3(M_Z), somewhat surprisingly, are found to be controlled by only a few effective parameters. This leads to a very predictive scenario for proton decay. As a novel feature, we find an interesting correlation between the d=6 (p\to e^+\pi^0) and d=5 (p\to \nu-bar K+) decay amplitudes which allows us to derive a constrained upper limit on the inverse rate of the e^+\pi^0 mode. Our results show that both modes should be observed with an improvement in the current sensitivity by about a factor of five to ten.Comment: 21 pages LaTeX, 2 figures, Few explanatory sentences and three new references added, minor typos corrected

    Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

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    Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes
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