Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) ...prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.
Steroid-resistant asthma comprises an important source of morbidity in patient populations. T(H)17 cells represent a distinct population of CD4(+) Th cells that mediate neutrophilic inflammation and ...are characterized by the production of IL-17, IL-22, and IL-6. To investigate the function of T(H)17 cells in the context of Ag-induced airway inflammation, we polarized naive CD4(+) T cells from DO11.10 OVA-specific TCR-transgenic mice to a T(H)2 or T(H)17 phenotype by culturing in conditioned medium. In addition, we also tested the steroid responsiveness of T(H)2 and T(H)17 cells. In vitro, T(H)17 cytokine responses were not sensitive to dexamethasone (DEX) treatment despite immunocytochemistry confirming glucocorticoid receptor translocation to the nucleus following treatment. Transfer of T(H)2 cells to mice challenged with OVA protein resulted in lymphocyte and eosinophil emigration into the lung that was markedly reduced by DEX treatment, whereas T(H)17 transfer resulted in increased CXC chemokine secretion and neutrophil influx that was not attenuated by DEX. Transfer of T(H)17 or T(H)2 cells was sufficient to induce airway hyperresponsiveness (AHR) to methacholine. Interestingly, AHR was not attenuated by DEX in the T(H)17 group. These data demonstrate that polarized Ag-specific T cells result in specific lung pathologies. Both T(H)2 and T(H)17 cells are able to induce AHR, whereas T(H)17 cell-mediated airway inflammation and AHR are steroid resistant, indicating a potential role for T(H)17 cells in steroid-resistant asthma.
Background. Invasive candidiasis is an important cause of morbidity and mortality among patients with health care–associated infection. The echinocandins have potent fungicidal activity against most ...Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. Methods. This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. Results. A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. Conclusions. Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.
•Demand response (DR) provides an efficient means to integrate RES and avoid surplus.•DR decreases the loading and amount of start-ups of peak and mid-peak power plants.•DR leads to lower operational ...cost, higher reliability and lower emission level.•More uncontrollable capacity in a generation portfolio increases DR benefits.•Scheduling battery electric vehicles brings higher societal value than scheduling white goods.
The future power system is characterized by more renewable and uncontrollable capacity at the supply side and an electrification of energy at the demand side. Both evolutions increase the need for flexibility in the power system. Although this flexibility can be triggered at the supply and demand side, the latter is often overlooked. In this perspective, this paper assesses the impact of the use of flexibility at the demand side, also referred to as demand response, on power system operation. A two-stage modeling approach is used which combines a day-ahead deterministic unit commitment model and an hourly simulation in real-time. This approach is tested for two alternative Belgian generation technology mix scenarios including a detailed representation of residential demand response. Hereby, realistic cycling patterns of white goods and mobility patterns of battery electric vehicles serve as an input. This approach allows to quantify operational benefits of demand response and to assess a potential introduction of demand response in power system operation. Results show that in general demand response contributes to a lower cost, higher reliability, and lower emission level of power system operation. Moreover, a higher amount of uncontrollable capacity increases these benefits and therefore the societal value of demand response.
Simulating the dynamic behaviour of heterogeneous finite-element structures such as electric motors often requires to homogenise the models in the first place. Current homogenisation methods do not ...always imply computing an equivalent homogeneous material׳s elasticity matrix and are often restrained to specific uses. In this document, a novel approach of equivalent material identification is developed for multi-layered orthotropic structures. A finite-element model of a 3D stratified structure is created, as well as its equivalent homogeneous medium. The dynamic behaviour of the homogeneous structure with the equivalent material identified by the new method is compared at low frequencies to the reference stack and to equivalent materials created using other existing homogenisation techniques. It is shown that this approach is more accurate than existing reference homogenisation methods. Applied to the magnetic core׳s finite-element model of a real laminated electric machine stator, the method enables simulating the experimental behaviour with good accuracy, without need of time-consuming model updating procedures.
•A method of material identification is proposed for multi-layered structures.•The method is compared to existing reference homogenisation techniques.•It is applied to the finite-element model of an electric machine stator.•New modelling guidelines for laminated stators are proposed.•The equivalent homogeneous material predicts the stator׳s modes accurately.
Multidisciplinary management of infra-peritoneal rectal cancer has pushed back the frontiers of sphincter preservation, without impairment of carcinological outcome. However, functional intestinal ...sequelae, grouping together several symptoms known under the name of anterior resection syndrome (ARS), have emerged and become an increasingly frequent concern for both patients and physicians. The pathophysiology is complex: ARS is a combination in various degrees of stool frequency, incontinence for flatus and/or stools, urgency, and disorders in discrimination and evacuation. The "Low Anterior Resection Score" (LARS), validated in 2012, is currently used to evaluate the severity of ARS and its impact on quality of life. While ARS can show improvement over the first two years, symptoms persist for longer than two years in nearly 60% of patients and in half of these patients, ARS is considered severe. The most frequently reported independent risk factors of severe ARS include neo-adjuvant radiation therapy, the extent of resection (total mesorectal excision that includes inter-sphincteric resection), absence of colonic pouch and anastomotic leak. In the absence of surgical complications and/or local recurrence, physicians can draw from a wide therapeutic armamentarium in order to improve the functional outcome of patients, including diet and lifestyle modifications, gut motility regulators, multimodal rehabilitation (biofeedback, electro-stimulation) and sacral nerve modulation. Permanent colostomy is an alternative of last resort, proposed only when all other solutions fail. A better understanding of the natural history of ARS, its risk factors as well as the array of therapeutic alternatives should provide better patient information and optimize management.
Polyphosphoinositides (PPIs) and in particular phosphatidylinositol-(4,5)-bisphosphate (PI4,5P2), control many cellular events and bind with variable levels of specificity to hundreds of ...intracellular proteins in vitro. The much more restricted targeting of proteins to PPIs in cell membranes is thought to result in part from the formation of spatially distinct PIP2 pools, but the mechanisms that cause formation and maintenance of PIP2 clusters are still under debate. The hypothesis that PIP2 forms submicrometer-sized clusters in the membrane by electrostatic interactions with intracellular divalent cations is tested here using lipid monolayer and bilayer model membranes. Competitive binding between Ca2+ and Mg2+ to PIP2 is quantified by surface pressure measurements and analyzed by a Langmuir competitive adsorption model. The physical chemical differences among three PIP2 isomers are also investigated. Addition of Ca2+ but not Mg2+, Zn2+, or polyamines to PIP2-containing monolayers induces surface pressure drops coincident with the formation of PIP2 clusters visualized by fluorescence, atomic force, and electron microscopy. Studies of bilayer membranes using steady-state probe-partitioning fluorescence resonance energy transfer (SP-FRET) and fluorescence correlation spectroscopy (FCS) also reveal divalent metal ion (Me2+)-induced cluster formation or diffusion retardation, which follows the trend: Ca2+ ≫ Mg2+ > Zn2+, and polyamines have minimal effects. These results suggest that divalent metal ions have substantial effects on PIP2 lateral organization at physiological concentrations, and local fluxes in their cytoplasmic levels can contribute to regulating protein–PIP2 interactions.
Electricity production from centralised and decentralised renewable energy resources in Europe is gaining significance, resulting in operational challenges in the electricity system. Although these ...challenges add to the locational and time dependency of the underlying cost of operating the system, this variability in time and location is not reflected in residential tariff schemes. Consequently, residential users are not incentivised to react to varying system conditions and to help the integration of renewable energy resources. Therefore, this paper provides a theoretical framework for designing a locational dynamic pricing scheme. This can be used to assess existing tariff structures for consumption and injection, and can serve as a theoretical background for developing new tariff schemes. Starting from the underlying costs, this paper shows that the potential for locational dynamic pricing depends on the locational and time dependency of its cost drivers. When converting costs into tariffs, the tariff design should be determined. This includes the advance notice of sending tariffs to users, and the length of price blocks and price patterns. This tariff design should find a balance between tariff principles related to costs, practicality and social acceptability on the one hand, and the resulting demand response incentive on the other.
•The integration of renewables affects the locational and time dependency of costs.•Locational dynamic pricing reflects cost variability and allows demand response.•A theoretical framework for designing and assessing tariff schemes is proposed.•Tariff variability depends on the locational & time dependency of its cost drivers.•The tariff design should consider the resulting demand response incentive.
The motion of a spherical particle along a rough bed in a simple shear viscous flow is studied experimentally for a wide range of parameters, varying the particle size and density, the fluid ...viscosity and the shear rate γ. The instantaneous particle velocity is calculated in the stream, transverse and vertical directions, using a high-speed video imaging system. It is found that the normalized streamwise mean particle velocity U/US, where US is the Stokes settling velocity, depends only on the dimensionless shear rate μ γ/(Δ ρ g d), this relationship being independent of the particle Reynolds number Rep. This result holds for small Rep, which was the case in our experiments (Rep < 10). The characteristic amplitude and frequency of the velocity fluctuations are also given and discussed. A model is then proposed for the mean streamwise velocity, based on ideas of Bagnold (Proc. R. Soc. Lond. A, vol. 332, 1973, p. 473) and calculations of Goldman et al. (Chem. Engng Sci., vol. 22, 1967b, p. 653) for the velocity of a particle close to a smooth plane. From this model an equivalent bed roughness and an effective friction coefficient are deduced.
Saltmarsh sparrows (
Ammospiza caudacuta
) and seaside sparrows (
A. maritima
) are species of conservation concern primarily due to global sea-level rise and habitat degradation. Environmental ...mercury (Hg) contamination may present additional threats to their reproductive success and survival. To assess site-specific total mercury (THg) exposure and identify environmental correlates of THg detection, we sampled blood from adult male saltmarsh and seaside sparrows at 27 sites between Maine and Virginia, USA. The mean THg concentration (±1 SD) throughout the entire sampling range was 0.531 ± 0.287 µg/g wet weight (ww) for saltmarsh sparrows and 0.442 ± 0.316 µg/g ww for seaside sparrows. Individual THg concentrations ranged from 0.135–1.420 µg/g ww for saltmarsh sparrows and 0.153–1.530 µg/g ww for seaside sparrows. Model averaging from a suite of linear mixed models showed that saltmarsh sparrows averaged 20.1% higher blood THg concentrations than seaside sparrows, potentially due to differences in diet or foraging behavior. We found no evidence for a relationship between sparrow THg concentrations and land cover surrounding sampled marshes or average precipitation-based Hg deposition. Overall, our results suggest considerable, unexplained variation in tidal marsh sparrow blood THg concentrations over their co-occurring breeding ranges.
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