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Fei Yan

Bio: Fei Yan is an academic researcher from University of Göttingen. The author has contributed to research in topics: Exoplanet & Planet. The author has an hindex of 32, co-authored 67 publications receiving 2871 citations. Previous affiliations of Fei Yan include European Southern Observatory & Max Planck Society.

Papers published on a yearly basis

Papers
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Journal ArticleDOI
TL;DR: Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.
Abstract: The influence of cytochrome P450 2D6 (CYP2D6) genetic variability was examined in psychiatric inpatients by evaluating adverse drug events (ADEs), hospital stays, and total costs over a 1-year period in an extension of a previously published brief report. One hundred consecutive psychiatric patients from Eastern State Hospital in Lexington, Kentucky, were genotyped for CYP2D6 expression. ADEs were evaluated by a neurologic rating scale, modified Udvalg for Kliniske Undersogelser Side Effect Rating Scale, or chart review. Information on total hospitalization days and total costs were gathered for a 1-year period. Forty-five percent of the patients received medications that were primarily dependent on the CYP2D6 enzyme for their elimination. When the analysis was restricted to just those patients in each group receiving medication heavily dependent on the CYP2D6 enzyme, the following were observed: (1) a trend toward greater numbers of ADEs from medications as one moved from the group with ultrarapid CYP2D6 activity (UM) to the group with absent CYP2D6 activity (PM); (2) the cost of treating patients with extremes in CYP2D6 activity (UM and PM) was on average $4,000 to $6,000 per year greater than the cost of treating patients in the efficient metabolizer (EM) and intermediate metabolizer (IM) groups; and (3) total duration of hospital stay was more pronounced for those in CYP2D6 PM group. Variance of hospital stays and costs calculated from these preliminary data suggests that 1,500 to 2,000 patients must be evaluated over at least a 1-year period to determine whether the CYP2D6 genetic variation significantly alters the duration of hospital stay and costs.

215 citations

Journal ArticleDOI
Ansgar Reiners1, Mathias Zechmeister1, Jose A. Caballero2, Ignasi Ribas3  +177 moreInstitutions (18)
TL;DR: In this article, the CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets and the authors present an atlas of high resolution M-dwarf spectra and compare the spectra to atmospheric models.
Abstract: The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least R >80 000, and we measure its RV, Hα emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, Q , and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s−1 in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s−1 .

199 citations

Journal ArticleDOI
TL;DR: In this paper, the authors present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models and demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star.
Abstract: The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520--1710nm at a resolution of at least $R > 80,000$, and we measure its RV, H$\alpha$ emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, $Q$, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700--900nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1ms$^{-1}$ in very low mass M dwarfs at longer wavelengths likely requires the use of a 10m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3-4ms$^{-1}$.

184 citations

Journal ArticleDOI
21 Dec 2018-Science
TL;DR: Ground-based high-resolution spectroscopy detected excess absorption in the helium triplet during the transit of the Saturn-mass exoplanet WASP-69b, which is interpreted as the escape of part of the atmosphere trailing behind the planet in comet-like form.
Abstract: Hot gas giant exoplanets can lose part of their atmosphere due to strong stellar irradiation, and these losses can affect their physical and chemical evolution. Studies of atmospheric escape from exoplanets have mostly relied on space-based observations of the hydrogen Lyman-α line in the far ultraviolet region, which is strongly affected by interstellar absorption. Using ground-based high-resolution spectroscopy, we detected excess absorption in the helium triplet at 1083 nanometers during the transit of the Saturn-mass exoplanet WASP-69b, at a signal-to-noise ratio of 18. We measured line blueshifts of several kilometers per second and posttransit absorption, which we interpret as the escape of part of the atmosphere trailing behind the planet in comet-like form.

171 citations

Journal ArticleDOI
TL;DR: In this article, the authors studied the atmosphere of one of these particular hot planets, MASCARA-2b/KELT-20b, using four transit observations with high resolution spectroscopy facilities.
Abstract: Ultra hot Jupiters orbit very close to their host star and consequently receive strong irradiation that makes their atmospheric chemistry different from the common gas giants. Here, we study the atmosphere of one of these particular hot planets, MASCARA-2b/KELT-20b, using four transit observations with high resolution spectroscopy facilities. Three of these observations were performed with HARPS-N and one with CARMENES. We simultaneously observed one of the transits with MuSCAT2 to monitor possible spots in the stellar surface. At high resolution, the transmission residuals show the effects of Rossiter-McLaughlin and center-to-limb variations from the stellar lines profiles, which we correct to finally extract the transmission spectra of the planet. We clearly observe absorption of CaII, FeII, NaI, H$\alpha$ and H$\beta$ in the atmosphere of MASCARA-2b, and indications of H$\gamma$ and MgI at low SNR. The results obtained with CARMENES and HARPS-N are consistent, measuring an H$\alpha$ absorption depth of $0.68\pm0.05\%$ and $0.59\pm0.07\%$, and NaI absorption of $0.11\pm0.04\%$ and $0.09\pm0.05\%$ ($0.75A$ passband), in both instruments respectively. For H$\beta$ only HARPS-N covers this wavelength range, measuring $0.28\pm0.06\%$ of absorption. The CaII is only covered with CARMENES, measuring an average absorption of $0.32\pm0.05\%$. Three additional FeII lines are observed in the transmission spectrum by HARPS-N, with mean absorption depth of $0.08\pm0.04\%$. The results presented here are consistent with theoretical models of ultra hot Jupiters atmospheres, suggesting the emergence of an ionised gas on the day-side of such planets. Ca and Fe, with other elements, are expected to be singly ionised at these temperatures and be more numerous than its neutral state. The CaII triplet lines are detected here for the first time in transmission in an exoplanet atmosphere.

148 citations


Cited by
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Journal ArticleDOI
TL;DR: Predictive CYP2D6 genotyping is estimated by the author to be beneficial for treatment of about 30–40% of CYP 2D6 drug substrates, that is, for about 7–10% of all drugs clinically used, although prospective clinical studies are necessary to evaluate the exact benefit of drug selection and dosage.
Abstract: CYP2D6 is of great importance for the metabolism of clinically used drugs and about 20–25% of those are metabolised by this enzyme. In addition, the enzyme utilises hydroxytryptamines as endogenous substrates. The polymorphism of the enzyme results in poor, intermediate, efficient or ultrarapid metabolisers (UMs) of CYP2D6 drugs. It is plausible that the UM genotype, where more than one active gene on one allele occurs, is the outcome of selective dietary selection in certain populations in North East Africa. The UM phenotype affects 5.5% of the population in Western Europe. A hypothesis for the evolutionary basis behind selection for CYP2D6 gene duplications is presented in relation to selection for Cyp6 variants in insecticide resistant Drosophila strains. The polymorphism of CYP2D6 significantly affects the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The consequences of the polymorphism at ordinary drug doses can be either adverse drug reactions or no drug response. Examples are presented where CYP2D6 polymorphism affects the efficacy and costs of drug treatment. Predictive CYP2D6 genotyping is estimated by the author to be beneficial for treatment of about 30–40% of CYP2D6 drug substrates, that is, for about 7–10% of all drugs clinically used, although prospective clinical studies are necessary to evaluate the exact benefit of drug selection and dosage based on the CYP2D6 genotype.

1,027 citations

Journal ArticleDOI
TL;DR: This article focuses on the cytochrome P-450 enzymes, a superfamily of microsomal drug-metabolizing enzymes that play an important role in oxidative drug metabolism.
Abstract: Differences in drug responsiveness are common, often leading to challenges in optimizing the dosage regimen for a particular patient. Recent advances provide a rational framework for understanding many interpatient differences in drug disposition and their clinical consequences. This article focuses on the cytochrome P-450 enzymes, a superfamily of microsomal drug-metabolizing enzymes that play an important role in oxidative drug metabolism.

1,004 citations

Journal ArticleDOI
TL;DR: The intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare, and more clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype.
Abstract: Of about one dozen human P450 s that catalyze biotransformations of xenobiotics, CYP2D6 is one of the more important ones based on the number of its drug substrates. It shows a very high degree of interindividual variability, which is primarily due to the extensive genetic polymorphism that influences expression and function. This so-called debrisoquine/sparteine oxidation polymorphism has been extensively studied in many different populations and over 80 alleles and allele variants have been described. CYP2D6 protein and enzymatic activity is completely absent in less than 1% of Asian people and in up to 10% of Caucasians with two null alleles, which do not encode a functional P450 protein product. The resulting "poor metabolizer" (PM) phenotype is characterized by the inability to use CYP2D6-dependent metabolic pathways for drug elimination, which affect up to 20% of all clinically used drugs. The consequences are increased risk of adverse drug reactions or lack of therapeutic response. Today, genetic testing predicts the PM phenotype with over 99% certainty. At the other extreme, the "Ultrarapid Metabolizer" (UM) phenotype can be caused by alleles carrying multiple gene copies. "Intermediate Metabolizers" (IM) are severely deficient in their metabolism capacity compared to normal "Extensive Metabolizers" (EM), but in contrast to PMs they express a low amount of residual activity due to the presence of at least one partially deficient allele. Whereas the intricate genetics of the CYP2D6 polymorphism is becoming apparent at ever greater detail, applications in clinical practice are still rare. More clinical studies are needed to show where patients benefit from drug dose adjustment based on their genotype. Computational approaches are used to predict and rationalize substrate specificity and enzymatic properties of CYP2D6. Pharmacophore modeling of ligands and protein homology modeling are two complementary approaches that have been applied with some success. CYP2D6 is not only expressed in liver but also in the gut and in brain neurons, where endogenous substrates with high-turnover have been found. Whether and how brain functions may be influenced by polymorphic expression are interesting questions for the future.

771 citations

Journal Article
TL;DR: Although genotype tests can determine if a patient has a specific enzyme polymorphism, it has not been determined if routine use of these tests will improve outcomes and knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inhibiting and inducing drugs, can help minimize the possibility of adverse drug reactions and interactions.
Abstract: Cytochrome P450 enzymes are essential for the metabolism of many medications. Although this class has more than 50 enzymes, six of them metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. Genetic variability (polymorphism) in these enzymes may influence a patient's response to commonly prescribed drug classes, including beta blockers and antidepressants. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes. Knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inhibiting and inducing drugs, can help minimize the possibility of adverse drug reactions and interactions. Although genotype tests can determine if a patient has a specific enzyme polymorphism, it has not been determined if routine use of these tests will improve outcomes.

757 citations

Journal ArticleDOI
Shu-Feng Zhou1
TL;DR: There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population and the number of alleles is still growing.
Abstract: Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (∼2–4%). There is a large interindividual variation in the enzyme activity of CYP2D6. The enzyme is largely non-inducible and metabolizes ∼25% of current drugs. Typical substrates for CYP2D6 are largely lipophilic bases and include some antidepressants, antipsychotics, antiarrhythmics, antiemetics, β-adrenoceptor antagonists (β-blockers) and opioids. The CYP2D6 activity ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population. To date, 74 allelic variants and a series of subvariants of the CYP2D6 gene have been reported and the number of alleles is still growing. Among these are fully functional alleles, alleles with reduced function and null (non-functional) alleles, which convey a wide range of enzyme activity, from no activity to ultrarapid metabolism of substrates. As a consequence, drug adverse effects or lack of drug effect may occur if standard doses are applied. The alleles *10, *17, *36 and *41 give rise to substrate-dependent decreased activity. Null alleles of CYP2D6 do not encode a functional protein and there is no detectable residual enzymatic activity. It is clear that alleles *3, *4, *5, *6, *7, *8, *11, *12, *13, *14, *15, *16, *18, *19, *20, *21, *38, *40, *42, *44, *56 and *62 have no enzyme activity. They are responsible for the PM phenotype when present in homozygous or compound heterozygous constellations. These alleles are of clinical significance as they often cause altered drug clearance and drug response. Among the most important variants are CYP2D6*2, *3, *4, *5, *10, *17 and *41. On the other hand, the CYP2D6 gene is subject to copy number variations that are often associated with the UM phenotype. Marked decreases in drug concentrations have been observed in UMs with tramadol, venlafaxine, morphine, mirtazapine and metoprolol. The functional impact of CYP2D6 alleles may be substrate-dependent. For example, CYP2D6*17 is generally considered as an allele with reduced function, but it displays remarkable variability in its activity towards substrates such as dextromethorphan, risperidone, codeine and haloperidol. The clinical consequence of the CYP2D6 polymorphism can be either occurrence of adverse drug reactions or altered drug response. Drugs that are most affected by CYP2D6 polymorphisms are commonly those in which CYP2D6 represents a substantial metabolic pathway either in the activation to form active metabolites or clearance of the agent. For example, encainide metabolites are more potent than the parent drug and thus QRS prolongation is more apparent in EMs than in PMs. In contrast, propafenone is a more potent b-blocker than its metabolites and the β-blocking activity during propafenone therapy is more prominent in PMs than EMs, as the parent drug accumulates in PMs. Since flecainide is mainly eliminated through renal excretion, and both R- and S-flecainide possess equivalent potency for sodium channel inhibition, the CYP2D6 phenotype has a minor impact on the response to flecainide. Since the contribution of CYP2D6 is greater for metoprolol than for carvedilol, propranolol and timolol, a stronger gene-dose effect is seen with this β-blocker, while such an effect is lesser or marginal in other β-blockers. Concordant genotype-phenotype correlation provides a basis for predicting the phenotype based on genetic testing, which has the potential to achieve optimal pharmacotherapy. However, genotype testing for CYP2D6 is not routinely performed in clinical practice and there is uncertainty regarding genotype-phenotype, gene-concentration and gene-dose relationships. Further prospective studies on the clinical impact of CYP2D6-dependent metabolism of drugs are warranted in large cohorts of subjects.

697 citations