Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

Antifúngic; Candidèmia; DesescaladaAntifúngico; Candidemia; DesescaladaAntifungal; Candidemia; De-escalationBackground There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. Methods This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed. Results Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53). Conclusions Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III

Probing the Star Formation Main Sequence down to 10810^{8} M⊙_\odot at 1.0<z<3.01.0<z<3.0

We investigate the star formation main sequence (MS) (SFR-M$_{\star}$) down to 10$^{8-9}\mathrm{M}_\odot$ using a sample of 34,061 newly-discovered ultra-faint ($27\lesssim i \lesssim 30$ mag) galaxies at $1<z<3$ detected in the GOODS-N field. Virtually these galaxies are not contained in previous public catalogs, effectively doubling the number of known sources in the field. The sample was constructed by stacking the optical broad-band observations taken by the HST/GOODS-CANDELS surveys as well as the 25 ultra-deep medium-band images gathered by the GTC/SHARDS project. Our sources are faint (average observed magnitudes $\sim28.2$ mag, $\sim27.9$ mag), blue (UV-slope $\sim-1.9$), star-forming (rest-frame colors $\sim0.10$ mag, $\sim0.17$ mag) galaxies. These observational characteristics are identified with young (mass-weighted age $\sim0.014$ Gyr) stellar populations subject to low attenuations ($\sim0.30$ mag). Our sample allows us to probe the MS down to $10^{8.0}\,\mathrm{M}_\odot$ at $z=1$ and $10^{8.5}\,\mathrm{M}_\odot$ at $z=3$, around 0.6 dex deeper than previous analysis. In the low-mass galaxy regime, we find an average value for the slope of 0.97 at $1<z<2$ and 1.12 at $2<z<3$. Nearly $\sim$60% of our sample presents stellar masses in the range $10^{6-8}$ M$_\odot$ between $1<z<3$. If the slope of the MS remained constant in this regime, the sources populating the low-mass tail of our sample would qualify as starburst galaxies.Comment: 34 pages, 16 figures, 9 tables. Accepted for publication to Ap

SHARDS: A global view of the star formation activity at z~0.84 and z~1.23

In this paper, we present a comprehensive analysis of star-forming galaxies (SFGs) at intermediate redshifts (z~1). We combine the ultra-deep optical spectro-photometric data from the Survey for High-z Absorption Red and Dead Sources (SHARDS) with deep UV-to-FIR observations in the GOODS-N field. Exploiting two of the 25 SHARDS medium-band filters, F687W17 and F823W17, we select [OII] emission line galaxies at z~0.84 and z~1.23 and characterize their physical properties. Their rest-frame equivalent widths (EW$_{\mathrm{rf}}$([OII])), line fluxes, luminosities, star formation rates (SFRs) and dust attenuation properties are investigated. The evolution of the EW$_{\mathrm{rf}}$([OII]) closely follows the SFR density evolution of the universe, with a trend of EW$_{\mathrm{rf}}$([OII])$\propto$(1+z)$^3$ up to redshift z~1, followed by a possible flattening. The SF properties of the galaxies selected on the basis of their [OII] emission are compared with complementary samples of SFGs selected by their MIR and FIR emission, and also with a general mass-selected sample of galaxies at the same redshifts. We demonstrate observationally that the UVJ diagram (or, similarly, a cut in the specific SFR) is only partially able to distinguish the quiescent galaxies from the SFGs. The SFR-M$_*$ relation is investigated for the different samples, yelding a logarithmic slope ~1, in good agreement with previous results. The dust attenuations derived from different SFR indicators (UV(1600), UV(2800), [OII], IR) are compared and show clear trends with respect to both the stellar mass and total SFR, with more massive and highly star-forming galaxies being affected by stronger dust attenuation.Comment: Replaced to match the accepted version (24 pages, 1 table, 17 figures). Published in ApJ, 812, 155 (2015): http://stacks.iop.org/0004-637X/812/15

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

[Background] There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection.[Methods] This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed.[Results] Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53).[Conclusions] Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III.Peer reviewe

The Paleolithic rock art of El Mirón (Ramales de la Victoria, Cantabria, Spain): a proposal for its stratigraphic dating

RESUMEN: Este artículo describe el arte parietal descubierto en la Cueva de El Mirón (Cantabria, España) en el curso de las excavaciones dirigidas en el yacimiento por MGM y LGS desde 1996. El arte consiste en grabados, la mayoría de ellos aparentemente no fi gurativos en su estado actual, pero hay una imagen de un caballo y otra de un posible bisonte. Todos los grabados se localizan en el fondo del gran vestíbulo, a plena luz, en íntima relación con los depósitos de origen humano. El caballo y los grabados lineales asociados a él en las paredes de la cueva pueden atribuirse al Magdaleniense inferior o medio sobre la base de su estilo y de la altura practicable sobre las superfi cies de ocupación de estos períodos. Datables con mayor precisión son dos grupos de grabados lineales sobre un gran bloque que pueden asignarse al Magdaleniense inferior cantábrico, un período bien caracterizado por sus obras de arte mueble, como los omóplatos grabados, en El Mirón y en otros varios yacimientos regionales. El bloque cayó de la pared de la cueva, con su cara exterior yaciendo sobre el nivel 110, datado por radiocarbono en 16.130 ± 250 y 16.520 ± 40 BP. A partir de entonces se grabó su cara originalmente interior. A continuación, el bloque y sus grabados fueron progresivamente recubiertos por sedimentos del Magdaleniense medio, superior y fi nal datados entre ca. 14.500- 12.000 BP. En suma, el arte descubierto y estudiado hasta la fecha en El Mirón puede atribuirse al Magdaleniense inferior y medio, aunque el yacimiento estuvo habitado por los humanos al menos desde el Paleolítico medio hasta época medieval. El artículo concluye situando el arte parietal de El Mirón en el contexto de las otras numerosas (pero peor datadas) manifestaciones de arte rupestre de la cuenca del río Asón, en la Cantabria Oriental, que incluyen sitios tan notables como Venta de la Perra, Covalanas, La Haza y Cullalvera.ABSTRACT: This article describes the rock art discovered in El Mirón Cave (Cantabria, Spain) during the course of excavations directed by LGS and MGM since 1996. The art consists of engravings: most are apparently non-representational in their currest condition, but there is one image of a horse and another of a possible bison. The engravings are all located at the rear of the large, sunlit vestibule of the cave, in intimate relationship with human habitation deposits. The horse and associated linear engravings on the cave wall can be attributed to the earlymiddle Magdalenian on the basis of style and practicable height above occupation surfaces of those periods. More precisely datable, two series of linear engravings on a large block can be assigned to the Lower Cantabrian Magdalenian, a period well-endowed with works of portable art, such as engraved scapulae, both at El Mirón and in many other regional sites. The block fell from the cave wall, its outer surface landing on Level 110, which is 14C-dated to 16,130 ± 250 and 16,520 ± 40 BP. Then the fl at inner surface of the block was engraved. Next, the block and the engravings were progressively covered over by sediments pertaining to Middle, Upper and Terminal Magdalenian levels 14C-dated between ca. 14,500- 12,000 BP. In sum, the art discovered to date in El Mirón can be attributed to the early and middle Magdalenian period, although the site itself was inhabited by humans from at least late Middle Paleolithic through Medieval times. This article concludes by placing the Mirón parietal art within the context of the numerous other (but less-well dated) cave art manifestations in the river Asón basin of eastern Cantabria, including such notable sites as Venta de la Perra, Covalanas, La Haza and Cullalvera

Efficacy of a strategy for implementing a guideline for the control of cardiovascular risk in a primary healthcare setting: the SIRVA2 study a controlled, blinded community intervention trial randomised by clusters

This work describes the methodology used to assess a strategy for implementing clinical practice guidelines (CPG) for cardiovascular risk control in a health area of Madrid

Negative responses of highland pines to anthropogenic activities in inland Spain: a palaeoecological perspective

Palaeoecological evidence indicates that highland pines were dominant in extensive areas of the mountains of Central and Northern Iberia during the first half of the Holocene. However, following several millennia of anthropogenic pressure, their natural ranges are now severely reduced. Although pines have been frequently viewed as first-stage successional species responding positively to human disturbance, some recent palaeobotanical work has proposed fire disturbance and human deforestation as the main drivers of this vegetation turnover. To assess the strength of the evidence for this hypothesis and to identify other possible explanations for this scenario, we review the available information on past vegetation change in the mountains of northern inland Iberia. We have chosen data from several sites that offer good chronological control, including palynological records with microscopic charcoal data and sites with plant macro- and megafossil occurrence. We conclude that although the available long-term data are still fragmentary and that new methods are needed for a better understanding of the ecological history of Iberia, fire events and human activities (probably modulated by climate) have triggered the pine demise at different locations and different temporal scales. In addition, all palaeoxylological, palynological and charcoal results obtained so far are fully compatible with a rapid human-induced ecological change that could have caused a range contraction of highland pines in western Iberia

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited