Abstract
Background
Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon ...sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role.
Methods
BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture.
Results
Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66–0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without 0.45 (IQR 0.10–0.84), 0.02 (IQR 0.004–0.09), respectively, and an increased interleukin (IL)-1β was associated with reduced species evenness (
r
s
= − 0.33,
p
< 0.01) and increased pathogenic bacteria presence (
r
s
= 0.28,
p
= 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89–0.998).
Conclusion
Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.
Abstract
As decommissioning of oil and gas (O&G) installations intensifies in the North Sea, and worldwide, debate rages regarding the fate of these novel habitats and their associated biota—a debate ...that has important implications for future decommissioning of offshore wind farms (OWFs). Calls to relax complete removal requirements in some circumstances and allow part of an O&G installation to be left in the marine environment are increasing. Yet knowledge regarding the biological communities that develop on these structures and their ecological role in the North Sea is currently insufficient to inform such decommissioning decisions. To focus debate regarding decommissioning policy and guide ecological research, we review environmental policy objectives in the region, summarize existing knowledge regarding ecological aspects of decommissioning for both O&G and OWF installations, and identify approaches to address knowledge gaps through science–industry collaboration. We find that in some cases complete removal will conflict with other policies regarding protection and restoration of reefs, as well as the conservation of species within the region. Key ecological considerations that are rarely considered during decommissioning decisions are: (i) provision of reef habitat, (ii) productivity of offshore ecosystems, (iii) enhancement of biodiversity, (iv) protection of the seabed from trawling, and (v) enhancement of connectivity. Knowledge gaps within these areas will best be addressed using industry infrastructure and vessels for scientific investigations, re-analysis of historical data held by industry, scientific training of industry personnel, joint research funding opportunities, and trial decommissioning projects.
We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the ...asymmetric broad profile of the electronic characteristic K α and K β x rays together with the hypersatellite Khα x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K - and L-shell hole production and their temporal evolution on the 10–20 fs scale during the muon cascade process.
During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less ...vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic.
Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and ...assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.
Candida infective endocarditis Baddley, J. W.; Benjamin, D. K.; Patel, M. ...
European journal of clinical microbiology & infectious diseases,
07/2008, Letnik:
27, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Candida
infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, ...treatment patterns, and outcomes of patients with
Candida
IE. We compared 33
Candida
IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with
Candida
IE were more likely to have prosthetic valves (
p
< 0.001), short-term indwelling catheters (
p
< 0.0001), and have healthcare-associated infections (
p
< 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%,
p
= 0.026) and persistent positive blood cultures (33.3% vs. 9.9%,
p
= 0.003) were more common among those with
Candida
IE. Mortality at discharge was higher in patients with
Candida
IE (30.3%) when compared to non-fungal cases (17%,
p
= 0.046). Among
Candida
patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%,
p
= 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of
Candida
IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define
Candida
IE.
ABSTRACT Transition Edge Sensor microcalorimeters can measure X-ray and gamma-ray energies with very high energy resolution and high photon-collection efficiency. For this technology to reach its ...full potential in future X-ray observatories, each sensor must be able to measure hundreds or even thousands of photon energies per second. Current "optimal filtering" approaches to achieve the best possible energy resolution work only for photons that are well isolated in time, a requirement which is in direct conflict with the need for high-rate measurements. We describe a new analysis procedure to allow fitting for the pulse height of all photons even in the presence of heavy pulse pile-up. In the limit of isolated pulses, the technique reduces to standard optimal filtering with long records. We employ reasonable approximations to the noise covariance function in order to render this procedure computationally viable even for very long data records. The technique is employed to analyze X-ray emission spectra at 600 eV and 6 keV at rates up to 250 counts s−1 in microcalorimeters having exponential signal decay times of approximately 1.2 ms.
We present Mars Atmosphere and Volatile EvolutioN (MAVEN) observations of low frequency steepened fast magnetosonic waves in the Martian magnetosphere and ionosphere. Solar wind pressure pulses ...generated in the upstream foreshock region impact the magnetopause and generate the magnetosonic waves within the magnetosphere, in a process analogous to the production of magnetic Pc pulsations in the terrestrial magnetosphere. The draped nature of the IMF about Mars, combined with the near‐perpendicular propagation of these waves across the magnetic field, act to channel these waves into the nightside ionosphere, where they are observed in their non‐linear steepened form. Coincident‐in‐time ion observations show that the light (H+) and heavy (O+, O2+, CO2+) planetary ion distribution functions possess significant suprathermal energetic tails, arising from wave‐particle interactions with the steepened waves. The short gyro period and small gyro radius of the protons, relative to the steepened waves, results in proton heating via adiabatic compression. In contrast, the long gyro period of the heavy ions relative to the wave frequency leads to nonadiabatic heating via wave‐trapping processes. The light and heavy ion species are heated above escape energy by these waves, even down close to the exobase. A limited statistical study of 101 neighboring orbits found that similar wave events occurred on 28% of orbits analyzed, suggesting that such wave‐heating events may be important drivers of the Mars nightside ionospheric dynamics and energy budget. Our discussion includes placing our results in the context of solar wind energy transfer to the ionospheres of unmagnetized and magnetized bodies in general.
Key Points
Linear and steepened magnetosonic waves are observed in the near Mars environment
Draped nature of IMF about Martian obstacle “channels” magnetosonic waves into nightside ionosphere
Adiabatic and nonadiabatic wave‐particle interaction processes heat light and heavy planetary ions
For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain ...unaddressed. Studies have consistently shown that ∼20% of patients with FL experience disease progression within 2years of first-line treatment, and consequently have a 50% risk of death in 5years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling. Prognostic methods to date have employed clinical parameters, genomic methods, and a wide assortment of biological and biochemical markers, but none so far has been able to adequately identify this high-risk population. Advances in the first-line treatment of FL with chemoimmunotherapy have led to a median progression-free survival (PFS) of approximately 7years; creating a challenge in the development of clinical trials where PFS is a primary end point. A surrogate end point that accurately predicts PFS would allow for new treatments to reach patients with FL sooner, or lessen toxicity, time, and expense to those patients requiring little to no therapy. Quality of response to treatment may predict PFS and overall survival in FL; as such complete response rates, either alone or in conjunction with PET imaging or minimal residual disease negativity, are being studied as surrogates, with complete response at 30months after induction providing the strongest surrogacy evidence to date. A better understanding of how to optimize quality of life in the context of this chronic illness is another important focus deserving of further study. Ongoing efforts to address these important unmet needs are herein discussed.
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