Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project

Background: Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. Methods/Design: Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. Discussion: We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. ClinicalTrials.gov identifier: NCT01154491

Deformation monitoring of dam infrastructures via spaceborne MT-InSAR. The case of La Viñuela (Málaga, southern Spain)

Dams require continuous security and monitoring programs, integrated with visual inspection and testing in dam surveillance programs. New approaches for dam monitoring focus on multi-sensor integration, taking into account emerging technologies such as GNSS, optic fiber, TLS, InSAR techniques, GBInSAR, GPR, that can be used as complementary data in dam monitoring, eliciting causes of dam deformation that cannot be assessed with traditional techniques. This paper presents a Multi-temporal InSAR (MT-InSAR) monitoring of La Viñuela dam (Málaga, Spain), a 96 m height earth-fill dam built from 1982 to 1989. The presented MT-InSAR monitoring system comprises three C-band radar (~5,7 cm wavelength) datasets from the European satellites ERS-1/2 (1992-2000), Envisat (2003-2008), and Sentinel-1A/B (2014-2018). ERS-1/2 and Envisat datasets were processed using StaMPS. In the case of Sentinel-1A/B, two different algorithms were applied, SARPROZ and ISCE-SALSIT, allowing the comparison of the estimated LOS velocity pattern. The obtained results confirm that LaViñuela dam is deforming since its construction, as an earth-fill dam. Maximum deformation rates were measured in the initial period (1992-2000), being around -7 mm/yr (LOS direction) on the coronation of the dam. In the period covered by the Envisat dataset (2003-2008), the average deforming pattern was lower, of the order of -4 mm/yr. Sentinel-1A/B monitoring confirms that the deformation is still active in the period 2014-2018 in the central-upper part of the dam, with maximums of velocity reaching -6 mm/yr. SARPROZ and ISCE-SALSIT algorithms provide similar results. It was concluded that MT-InSAR techniques can support the development of new and more effective means of monitoring and analyzing the health of dams complementing actual dam surveillance systems

Epidemiology and cost of herpes zoster and postherpetic neuralgia among patients treated in primary care centres in the valencian community of Spain

<p>Abstract</p> <p>Background</p> <p>Data on the epidemiology and costs related to herpes zoster (HZ) and postherpetic neuralgia (PHN) in Spain are scarce; therefore, studies are needed to evaluate the epidemiological and economic impact of HZ and its most common complication, PHN. The present study aimed to estimate the clinical and economic burden of HZ and PHN in Valencia (Spain).</p> <p>Methods</p> <p>We prospectively analyzed the burden of HZ and PHN and their attributable costs in patients from 25 general practices in the Autonomous Community of Valencia serving 36,030 persons aged > 14 years. All patients with a clinical diagnosis of HZ who attended these centers between December 1^st2006 and November 30^th2007 were asked to participate. Patients included were followed for 1 year.</p> <p>Results</p> <p>Of the 130 cases of HZ followed up, continued pain was experienced by 47.6% (95% confidence interval (CI) = 35.6-56.7%) at 1 month after rash onset, by 14.5% (95% CI = 7.8-1.2%) at 3 months, by 9.0% (95% CI = 3.7-14.3%) at 6 months, and by 5.9% (95% CI = 1.5-10.3%) at 12 months. The percentage of patients with PHN increased with age, from 21.4% (95% CI = 8.3-40) in patients < 50 years to 59.2% (95% CI = 44.4-74) in patients ≥ 70 years. The estimated total cost for the 130 HZ cases during the follow-up period was €49,160 ($67,349). Mean cost per patient was €378 (range 53-2,830) ($517, range 73-3,877).</p> <p>Conclusions</p> <p>This study shows that PHN is a relatively common complication of HZ and that both conditions combined give rise to a significant clinical and economic burden for patients and providers.</p

Antifungal susceptibility of invasive yeast isolates in Italy: the GISIA3 study in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Yeasts are a common cause of invasive fungal infections in critically ill patients. Antifungal susceptibility testing results of clinically significant fungal strains are of interest to physicians, enabling them to adopt appropriate strategies for empiric and prophylactic therapies. We investigated the antifungal susceptibility of yeasts isolated over a 2-year period from hospitalised patients with invasive yeast infections.</p> <p>Methods</p> <p>638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC) and two co-ordinating centres (CC). The Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method was used at the CCs for comparison.</p> <p>Results</p> <p>Etest and Sensititre (LC/CC) MIC₉₀values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC₉₀values were influenced by the reduced susceptibility of <it>Candida parapsilosis </it>isolates to echinocandins and a reduced or lack of susceptibility of <it>Candida glabrata </it>and <it>Candida krusei </it>to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre), and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre); differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected.</p> <p>Conclusions</p> <p>Our data confirm the different antifungal susceptibility patterns among species, and highlight the need to perform antifungal susceptibility testing of clinically relevant yeasts. With the exception of a few species (e.g. <it>C. glabrata </it>for azoles and <it>C. parapsilosis </it>for echinocandins), the findings of our study suggest that two of the most widely used commercial methods (Etest and Sensititre) provide valid and reproducible results.</p

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Identification of Yeasts Is Contingent on Robust Reference Spectra

BACKGROUND: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast identification is limited by the requirement for protein extraction and for robust reference spectra across yeast species in databases. We evaluated its ability to identify a range of yeasts in comparison with phenotypic methods. METHODS: MALDI-TOF MS was performed on 30 reference and 167 clinical isolates followed by prospective examination of 67 clinical strains in parallel with biochemical testing (total n = 264). Discordant/unreliable identifications were resolved by sequencing of the internal transcribed spacer region of the rRNA gene cluster. PRINCIPAL FINDINGS: Twenty (67%; 16 species), and 24 (80%) of 30 reference strains were identified to species, (spectral score ≥2.0) and genus (score ≥1.70)-level, respectively. Of clinical isolates, 140/167 (84%) strains were correctly identified with scores of ≥2.0 and 160/167 (96%) with scores of ≥1.70; amongst Candida spp. (n = 148), correct species assignment at scores of ≥2.0, and ≥1.70 was obtained for 86% and 96% isolates, respectively (vs. 76.4% by biochemical methods). Prospectively, species-level identification was achieved for 79% of isolates, whilst 91% and 94% of strains yielded scores of ≥1.90 and ≥1.70, respectively (100% isolates identified by biochemical methods). All test scores of 1.70-1.90 provided correct species assignment despite being identified to "genus-level". MALDI-TOF MS identified uncommon Candida spp., differentiated Candida parapsilosis from C. orthopsilosis and C. metapsilosis and distinguished between C. glabrata, C. nivariensis and C. bracarensis. Yeasts with scores of <1.70 were rare species such as C. nivariensis (3/10 strains) and C. bracarensis (n = 1) but included 4/12 Cryptococcus neoformans. There were no misidentifications. Four novel species-specific spectra were obtained. Protein extraction was essential for reliable results. CONCLUSIONS: MALDI-TOF MS enabled rapid, reliable identification of clinically-important yeasts. The addition of spectra to databases and reduction in identification scores required for species-level identification may improve its utility

Glucose Recovery from Different Corn Stover Fractions Using Dilute Acid and Alkaline Pretreatment Techniques

Background: Limited availability of corn stover due to the competing uses (organic manure, animal feed, bio-materials, and bioenergy) presents a major concern for its future in the bio-economy. Furthermore, biomass research has exhibited different results due to the differences in the supply of enzymes and dissimilar analytical methods. The effect of the two leading pretreatment techniques (dilute acid and alkaline) on glucose yield from three corn stover fractions (cob, stalk, and leaf) sourced from a single harvest in Uganda were studied at temperatures 100, 120, 140, and 160 °C over reaction times of 5, 10, 30, and 60 min. Results: From this study, the highest glucose concentrations obtained from the dilute acid (DA) pretreated cobs, stalks, and leaves were 18.4 g/L (66.8% glucose yield), 16.2 g/L (64.1% glucose yield), and 11.0 g/L (49.5% glucose yield), respectively. The optimal pretreatment settings needed to obtain these yields from the DA pretreated samples were at a temperature of 160 °C over an incubation time of 30 min. The highest glucose concentrations obtained from the alkaline (AL) pretreated cobs, stalks, and leaves were 24.7 g/L (81.73% glucose yield), 21.3 g/L (81.23% glucose yield), and 15.0 g/L (51.92% glucose yield), respectively. To be able to achieve these yields, the optimal pretreatment settings for the cobs and stalks were 140 °C and for a retention time of 30 min, while the leaves require optimal conditions of 140 °C and for a retention time of 60 min. Conclusions: The study recommends that the leaves could be left on the field during harvesting since the recovery of glucose from the pretreated cobs and stalks is higher