The CLSI Antifungal Subcommittee followed the M23-A2 "blueprint" to develop interpretive MIC breakpoints for anidulafungin, caspofungin, and micafungin against Candida species. MICs of <=2 μg/ml for ...all three echinocandins encompass 98.8 to 100% of all clinical isolates of Candida spp. without bisecting any species group and represent a concentration that is easily maintained throughout the dosing period. Data from phase III clinical trials demonstrate that the standard dosing regimens for each of these agents may be used to treat infections due to Candida spp. for which MICs are as high as 2 μg/ml. An MIC predictive of resistance to these agents cannot be defined based on the data from clinical trials due to the paucity of isolates for which MICs exceed 2 μg/ml. The clinical data set included only three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were >2 μg/ml (two C. parapsilosis isolates at 4 μg/ml and one C. rugosa isolate at 8 μg/ml). Based on these data, the CLSI subcommittee has decided to recommend a "susceptible only" breakpoint MIC of <=2 μg/ml due to the lack of echinocandin resistance in the population of Candida isolates thus far. Isolates for which MICs exceed 2 μg/ml should be designated "nonsusceptible" (NS). For strains yielding results suggestive of an NS category, the organism identification and antimicrobial-susceptibility test results should be confirmed. Subsequently, the isolates should be submitted to a reference laboratory that will confirm the results by using a CLSI reference dilution method.
Abstract
We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of ...Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s
−1
and FWHM ranging from ∼500 to 1100 km s
−1
. The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1–2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H
2
emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s
−1
. We estimate a total mass of warm H
2
gas of ∼1.2 × 10
7
M
⊙
in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2
μ
m PAH feature with an equivalent width of ∼0.07
μ
m and a flux of 2.7 × 10
−17
W m
−2
is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes.
Highlights • A review of the current status of Geant4-DNA is presented. • New physical models describing the interactions of electrons in water are described. • Physicochemical and chemical stages of ...water radiolysis can be simulated. • Several approaches are available for modeling geometries of biological targets. • Dedicated examples are proposed to demonstrate such capabilities.
Abstract
We present results from the James Webb Space Telescope Director’s Discretionary Time Early Release Science program 1328 targeting the nearby, luminous infrared galaxy, VV 114. We use the ...MIRI and NIRSpec instruments to obtain integral-field spectroscopy of the heavily obscured eastern nucleus (V114E) and surrounding regions. The spatially resolved, high-resolution spectra reveal the physical conditions in the gas and dust over a projected area of 2–3 kpc that includes the two brightest IR sources, the NE and SW cores. Our observations show for the first time spectroscopic evidence that the SW core hosts an active galactic nucleus as evidenced by its very low 6.2
μ
m and 3.3
μ
m polycyclic aromatic hydrocarbon equivalent widths (0.12 and 0.017
μ
m, respectively) and mid- and near-IR colors. Our observations of the NE core show signs of deeply embedded star formation including absorption features due to aliphatic hydrocarbons, large quantities of amorphous silicates, as well as HCN due to cool gas along the line of sight. We detect elevated Fe
ii
/Pf
α
consistent with extended shocks coincident with enhanced emission from warm H
2
, far from the IR-bright cores and clumps. We also identify broadening and multiple kinematic components in both H
2
and fine structure lines caused by outflows and previously identified tidal features.
We present a large-scale clustering analysis of radio galaxies in the Very Large Array Faint Images of the Radio Sky at Twenty-cm survey over the Galaxy and Mass Assembly (GAMA) survey area, limited ...to S
1.4 GHz > 1 mJy with spectroscopic and photometric redshift limits up to r < 19.8 and <22 mag, respectively. For the GAMA spectroscopic matches, we present the redshift space and projected correlation functions, the latter of which yielding a correlation length r
0 ∼ 8.2 h
−1 Mpc and linear bias of ∼1.9 at z ∼ 0.34. Furthermore, we use the angular two-point correlation function w(θ) to determine spatial clustering properties at higher redshifts. We find r
0 to increase from ∼6 to ∼14 h
−1 Mpc between z = 0.3 and 1.55, with the corresponding bias increasing from ∼2 to ∼10 over the same range. Our results are consistent with the bias prescription implemented in the SKA Design Study simulations at low redshift, but exceed these predictions at z > 1. This is indicative of an increasing (rather than fixed) halo mass and/or active galactic nuclei fraction at higher redshifts or a larger typical halo mass for the more abundant Fanaroff and Riley Class I sources.
We compare common star formation rate (SFR) indicators in the local Universe in the Galaxy and Mass Assembly (GAMA) equatorial fields (∼160 deg2), using ultraviolet (UV) photometry from GALEX, ...far-infrared and sub-millimetre (sub-mm) photometry from Herschel Astrophysical Terahertz Large Area Survey, and Hα spectroscopy from the GAMA survey. With a high-quality sample of 745 galaxies (median redshift 〈z〉 = 0.08), we consider three SFR tracers: UV luminosity corrected for dust attenuation using the UV spectral slope β (SFRUV, corr), Hα line luminosity corrected for dust using the Balmer decrement (BD) (SFRH α, corr), and the combination of UV and infrared (IR) emission (SFRUV + IR). We demonstrate that SFRUV, corr can be reconciled with the other two tracers after applying attenuation corrections by calibrating Infrared excess (IRX; i.e. the IR to UV luminosity ratio) and attenuation in the Hα (derived from BD) against β. However, β, on its own, is very unlikely to be a reliable attenuation indicator. We find that attenuation correction factors depend on parameters such as stellar mass (M
*), z and dust temperature (T
dust), but not on Hα equivalent width or Sérsic index. Due to the large scatter in the IRX versus β correlation, when compared to SFRUV + IR, the β-corrected SFRUV, corr exhibits systematic deviations as a function of IRX, BD and T
dust.
Iron is an essential nutrient that plays a complex role in cancer biology. Iron metabolism must be tightly controlled within cells. Whilst fundamental to many cellular processes and required for cell ...survival, excess labile iron is toxic to cells. Increased iron metabolism is associated with malignant transformation, cancer progression, drug resistance and immune evasion. Depleting intracellular iron stores, either with the use of iron chelating agents or mimicking endogenous regulation mechanisms, such as microRNAs, present attractive therapeutic opportunities, some of which are currently under clinical investigation. Alternatively, iron overload can result in a form of regulated cell death, ferroptosis, which can be activated in cancer cells presenting an alternative anti-cancer strategy. This review focuses on alterations in iron metabolism that enable cancer cells to meet metabolic demands required during different stages of tumorigenesis in relation to metastasis and immune response. The strength of current evidence is considered, gaps in knowledge are highlighted and controversies relating to the role of iron and therapeutic targeting potential are discussed. The key question we address within this review is whether iron modulation represents a useful approach for treating metastatic disease and whether it could be employed in combination with existing targeted drugs and immune-based therapies to enhance their efficacy.
Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and ...virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East.
Abstract The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. ...An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non–high-density lipoprotein cholesterol and low-density lipoprotein cholesterol LDL-C, termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.
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