This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature ...is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype‐guided warfarin dosing to achieve a target international normalized ratio of 2–3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
We demonstrated coherent control of a quantum two-level system based on two-electron spin states in a double quantum dot, allowing state preparation, coherent manipulation, and projective readout. ...These techniques are based on rapid electrical control of the exchange interaction. Separating and later recombining a singlet spin state provided a measurement of the spin dephasing time, T₂*, of approximately10 nanoseconds, limited by hyperfine interactions with the gallium arsenide host nuclei. Rabi oscillations of two-electron spin states were demonstrated, and spin-echo pulse sequences were used to suppress hyperfine-induced dephasing. Using these quantum control techniques, a coherence time for two-electron spin states exceeding 1 microsecond was observed.
The Morphometry of Impact Craters on Bennu Daly, R. T.; Bierhaus, E. B.; Barnouin, O. S. ...
Geophysical research letters,
28 December 2020, Letnik:
47, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Bennu is an ~500‐m‐diameter rubble‐pile asteroid that is the target of detailed study by the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) ...mission. Here we use data from the OSIRIS‐REx Laser Altimeter to assess depth‐to‐diameter ratios (d/D) of 108 impact craters larger than 10 m in diameter. The d/D of craters on Bennu ranges from 0.02 to 0.19. The mean is 0.10 ± 0.03. The smallest craters show the broadest range in d/D, consistent with d/D measurements on other asteroids. A few craters have central mounds, which is interpreted as evidence that a more competent substrate lies a few meters beneath them. The range of d/D narrows as crater size increases, with craters larger than 80 m tending toward smaller d/D. At large scales, increases in target strength with depth, combined with target curvature, may affect crater morphometry.
Plain Language Summary
Between 2018 and 2020, National Aeronautics and Space Administration (NASA)'s Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS‐REx) spacecraft orbited a small asteroid called Bennu in preparation to collect a sample for return to Earth. Bennu is a “rubble‐pile” asteroid, meaning an aggregate of rock fragments that have coalesced together in space. OSIRIS‐REx observations showed that Bennu has many craters on its surface, which formed when other, smaller objects collided with it in the past. Crater depths and widths (diameters), in addition to relating to the size and speed of the impacting object, also reflect the physical characteristics of the impacted surface. Accordingly, we measured the depths and diameters of many of Bennu's craters to better understand the surface and interior properties of this rubble‐pile asteroid and how it compares to other asteroids. The smaller craters on Bennu have a variety of depths, even among similarly sized craters. The largest are so wide that they appear to be affected by the curvature of Bennu's surface and by the presence of stronger material at depth. We observe mounds inside some of the smaller craters, supporting the idea that a more competent substrate underlies the surface material.
Key Points
The depth‐to‐diameter ratio (d/D) of asteroid Bennu's craters >10 m in diameter ranges from 0.02 to 0.19 with a mean of 0.10 ± 0.03
Small craters show the greatest diversity in d/D, whereas larger craters (>80 m) span a narrower range in d/D and tend to be shallower
For craters >80 m, increases in target strength with depth, combined with target curvature, likely contribute to smaller d/D
This systematic review evaluated the evidence comparing patient-important outcomes in spinal or epidural vs general anaesthesia for total hip and total knee arthroplasty.
MEDLINE, Ovid EMBASE, EBSCO ...CINAHL, Thomson Reuters Web of Science, and the Cochrane Central Register of Controlled Trials from inception until March 2015 were searched. Eligible randomized controlled trials or prospective comparative studies investigating mortality, major morbidity, and patient-experience outcomes directly comparing neuraxial (spinal or epidural) with general anaesthesia for total hip arthroplasty, total knee arthroplasty, or both were included. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. Meta-analysis was conducted using the random-effects model.
We included 29 studies involving 10 488 patients. Compared with general anaesthesia, neuraxial anaesthesia significantly reduced length of stay (weighted mean difference −0.40 days; 95% confidence interval −0.76 to −0.03; P+0.03; I2 73%; 12 studies). No statistically significant differences were found between neuraxial and general anaesthesia for mortality, surgical duration, surgical site or chest infections, nerve palsies, postoperative nausea and vomiting, or thromboembolic disease when antithrombotic prophylaxis was used. Subgroup analyses failed to find statistically significant interactions (P>0.05) based on risk of bias, type of surgery, or type of neuraxial anaesthesia.
Neuraxial anaesthesia for total hip or total knee arthroplasty, or both appears equally effective without increased morbidity when compared with general anaesthesia. There is limited quantitative evidence to suggest that neuraxial anaesthesia is associated with improved perioperative outcomes. Future investigations should compare intermediate and long-term outcome differences to better inform anaesthesiologists, surgeons, and patients on importance of anaesthetic selection.
There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of ...the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.
Summary
Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the ...initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW‐recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene‐targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9‐associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome.
Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the ...cytochrome P450–2C9 (CYP2C9) and vitamin K–epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer–reviewed gene–drug guidelines that are published and updated periodically on http://www.pharmgkb.org based on new developments in the field.1
Clinical Pharmacology & Therapeutics (2011) 90 4, 625–629. doi:10.1038/clpt.2011.185
•We show deep learning to extract features from structured tabular data.•We apply information-fusion-based sensitivity analysis to feature importance.•Deep learning-based features enable more ...accurate classification of trader risk.•Deep learning-based risk management increases profits in our case study.
The paper examines the potential of deep learning to support decisions in financial risk management. We develop a deep learning model for predicting whether individual spread traders secure profits from future trades. This task embodies typical modeling challenges faced in risk and behavior forecasting. Conventional machine learning requires data that is representative of the feature-target relationship and relies on the often costly development, maintenance, and revision of handcrafted features. Consequently, modeling highly variable, heterogeneous patterns such as trader behavior is challenging. Deep learning promises a remedy. Learning hierarchical distributed representations of the data in an automatic manner (e.g. risk taking behavior), it uncovers generative features that determine the target (e.g., trader’s profitability), avoids manual feature engineering, and is more robust toward change (e.g. dynamic market conditions). The results of employing a deep network for operational risk forecasting confirm the feature learning capability of deep learning, provide guidance on designing a suitable network architecture and demonstrate the superiority of deep learning over machine learning and rule-based benchmarks.
Abstract
We present a MUSE (Multi-Unit Spectroscopic Explorer) and KMOS (K-band Multi-Object Spectrograph) dynamical study 405 star-forming galaxies
at redshift z = 0.28–1.65 (median redshift
...$\bar{z}$
= 0.84). Our sample is representative of the star-forming ‘main sequence’, with star formation rates of SFR = 0.1–30 M⊙ yr−1 and stellar masses M
⋆ = 108–1011 M⊙. For 49 ± 4 per cent of our sample, the dynamics suggest rotational support, 24 ± 3 per cent are unresolved systems and 5 ± 2 per cent appear to be early-stage major mergers with components on 8–30 kpc scales. The remaining 22 ± 5 per cent appear to be dynamically complex, irregular (or face-on systems). For galaxies whose dynamics suggest rotational support, we derive inclination-corrected rotational velocities and show that these systems lie on a similar scaling between stellar mass and specific angular momentum as local spirals with j
⋆ = J/
$M_\star \propto M_\star ^{2/3}$
but with a redshift evolution that scales as j
⋆ ∝ M
$_\star ^{2/3}(1+z)^{-1}$
. We also identify a correlation between specific angular momentum and disc stability such that galaxies with the highest specific angular momentum (log(j
⋆/M
$_\star ^{2/3}$
) > 2.5) are the most stable, with Toomre Q = 1.10 ± 0.18, compared to Q = 0.53 ± 0.22 for galaxies with log(j
⋆/M
$_\star ^{2/3}$
) < 2.5. At a fixed mass, the Hubble Space Telescope morphologies of galaxies with the highest specific angular momentum resemble spiral galaxies, whilst those with low specific angular momentum are morphologically complex and dominated by several bright star-forming regions. This suggests that angular momentum plays a major role in defining the stability of gas discs: at z ∼ 1, massive galaxies that have discs with low specific angular momentum are globally unstable, clumpy and turbulent systems. In contrast, galaxies with high specific angular momentum have evolved into stable discs with spiral structure where star formation is a local (rather than global) process.
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