AbstractObjectiveTo determine the presence of a set of pre-specified traditional and non-traditional criteria used to assess scientists for promotion and tenure in faculties of biomedical sciences ...among universities worldwide.DesignCross sectional study.SettingInternational sample of universities.Participants170 randomly selected universities from the Leiden ranking of world universities list.Main outcome measurePresence of five traditional (for example, number of publications) and seven non-traditional (for example, data sharing) criteria in guidelines for assessing assistant professors, associate professors, and professors and the granting of tenure in institutions with biomedical faculties.ResultsA total of 146 institutions had faculties of biomedical sciences, and 92 had eligible guidelines available for review. Traditional criteria of peer reviewed publications, authorship order, journal impact factor, grant funding, and national or international reputation were mentioned in 95% (n=87), 37% (34), 28% (26), 67% (62), and 48% (44) of the guidelines, respectively. Conversely, among non-traditional criteria, only citations (any mention in 26%; n=24) and accommodations for employment leave (37%; 34) were relatively commonly mentioned. Mention of alternative metrics for sharing research (3%; n=3) and data sharing (1%; 1) was rare, and three criteria (publishing in open access mediums, registering research, and adhering to reporting guidelines) were not found in any guidelines reviewed. Among guidelines for assessing promotion to full professor, traditional criteria were more commonly reported than non-traditional criteria (traditional criteria 54.2%, non-traditional items 9.5%; mean difference 44.8%, 95% confidence interval 39.6% to 50.0%; P=0.001). Notable differences were observed across continents in whether guidelines were accessible (Australia 100% (6/6), North America 97% (28/29), Europe 50% (27/54), Asia 58% (29/50), South America 17% (1/6)), with more subtle differences in the use of specific criteria.ConclusionsThis study shows that the evaluation of scientists emphasises traditional criteria as opposed to non-traditional criteria. This may reinforce research practices that are known to be problematic while insufficiently supporting the conduct of better quality research and open science. Institutions should consider incentivising non-traditional criteria.Study registrationOpen Science Framework (https://osf.io/26ucp/?view_only=b80d2bc7416543639f577c1b8f756e44).
Background and aims
Liver transplantation (LT) in alcohol‐associated hepatitis (AH) remains controversial, in part because spontaneous recovery (SR) can occur. There is a paucity of data on SR in ...patients with severe AH who undergo LT evaluation. The purpose of this study was to determine factors associated with SR and survival in patients with severe AH who undergo LT evaluation.
Approach and results
This is a retrospective study of ALD patients with Model for End‐Stage Liver Disease (MELD) >25 and <90 days abstinence who underwent LT evaluation at a single center between 2012 and 2018. One hundred forty‐four patients (median age, 45.5 years; 68.1% male) were included. Forty‐nine (34%) underwent LT and 95 (66%) patients did not undergo LT, and of those, 34 (23.6%) experienced SR. Factors associated with recovery were younger age (OR, 0.92; p = 0.004), lower index international normalized ratio (INR; 0.31; p = 0.03), and lower peak MELD (OR, 0.83; p = 0.02). Only 7 patients (20.6%) achieved a compensated state with a MELD <15 and absence of therapy for ascites or HE. Survival was improved in patients who underwent early LT when compared to SR. Survival was impaired in SR following relapse to alcohol use when compared to SR patients who abstained and LT recipients. Among all 6‐month survivors of AH, alcohol use trended toward an association with mortality (HR, 2.05; p = 0.17), but only LT was associated with decreased mortality risk (HR, 0.20; p = 0.005).
Conclusions
SR from AH after LT evaluation is associated with age, index INR, and lower peak MELD. Most recovered patients continue to experience end‐stage complications. LT is the only factor associated with lower mortality.
The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without ...mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients.
We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained.
Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval CI, 89%–97%) and 84% at 3 years (95% CI, 75%–90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%–34%) and 34% at 3 years (95% CI, 25%–44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%–18%) and 17% at 3 years (95% CI, 10%–27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01).
In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.
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A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority ...of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, beta = -0.11, P = 4.997 x 10.sup.-8 ), and an additional 201 suggestively significant variants. Four genes are associated with rs72884519: TMEM241, RIOK3, NPC1, and RMC1. Using the Functional Mapping and Annotation (FUMA) platform and the Multi-marker Analysis of GenoMic Annotation (MAGMA) tool, we identified 34 genes with a possible role in vegetarianism, 3 of which are GWAS-significant based on gene-level analysis: RIOK3, RMC1, and NPC1. Several of the genes associated with vegetarianism, including TMEM241, NPC1, and RMC1, have important functions in lipid metabolism and brain function, raising the possibility that differences in lipid metabolism and their effects on the brain may underlie the ability to subsist on a vegetarian diet. These results support a role for genetics in choosing a vegetarian diet and open the door to future studies aimed at further elucidating the physiologic pathways involved in vegetarianism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
genome-wide association study of alcohol dependence Bierut, Laura J; Agrawal, Arpana; Bucholz, Kathleen K ...
Proceedings of the National Academy of Sciences - PNAS,
03/2010, Letnik:
107, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol ...dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10⁻⁵, but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the most common cancers worldwide and accounts for substantial morbidity and mortality. Chronic hepatitis B virus (HBV) ...infection, chronic hepatitis C virus (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most important etiologies of HCC, and effective screening and management strategies are crucial to reduce the HCC risk. For HBV, which accounts for the majority of HCC cases, most infections were acquired via perinatal and early horizontal transmission. Universal vaccination of newborns has led to a decline in HCC incidence compared with the pre-vaccination era. Effective antiviral therapies with nucleos(t)ide analogues or pegylated interferon reduced the incidence of HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has substantially improved cure rates; therefore all patients with HCV should be considered for DAA treatment. The most important obstacle in eliminating HCV is access to therapy. For NAFLD, the global incidence is increasing rapidly, thus its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative while drug therapy has yet to demonstrate substantive protective effects on HCC prevention. For management of HCC, early diagnosis via imaging surveillance among persons with HCC risk factors remains the most important strategy to identify early-stage disease appropriate for resection or transplantation.
Early liver transplant (LT) for alcohol‐associated disease (i.e., without a specific sobriety period) is controversial but increasingly used. Using the multicenter American Consortium of Early Liver ...Transplantation for Alcoholic Hepatitis (ACCELERATE‐AH) cohort, we aimed to develop a predictive tool to identify patients pretransplant with low risk for sustained alcohol use posttransplant to inform selection of candidates for early LT. We included consecutive ACCELERATE‐AH LT recipients between 2012 and 2017. All had clinically diagnosed severe alcoholic hepatitis (AH), no prior diagnosis of liver disease or AH, and underwent LT without a specific sobriety period. Logistic and Cox regression, classification and regression trees (CARTs), and least absolute shrinkage and selection operator (LASSO) regression were used to identify variables associated with sustained alcohol use post‐LT. Among 134 LT recipients for AH with median period of alcohol abstinence pre‐LT of 54 days, 74% were abstinent, 16% had slips only, and 10% had sustained alcohol use after a median 1.6 (interquartile range IQR: 0.7‐2.8) years follow‐up post‐LT. Four variables were associated with sustained use of alcohol post‐LT, forming the Sustained Alcohol Use Post‐LT (SALT) score (range: 0‐11): >10 drinks per day at initial hospitalization (+4 points), multiple prior rehabilitation attempts (+4 points), prior alcohol‐related legal issues (+2 points), and prior illicit substance abuse (+1 point). The C statistic was 0.76 (95% confidence interval CI: 0.68‐0.83). A SALT score ≥5 had a 25% positive predictive value (95% CI: 10%‐47%) and a SALT score of <5 had a 95% negative predictive value (95% CI: 89%‐98%) for sustained alcohol use post‐LT. In internal cross‐validation, the average C statistic was 0.74. Conclusion: A prognostic score, the SALT score, using four objective pretransplant variables identifies candidates with AH for early LT who are at low risk for sustained alcohol use posttransplant. This tool may assist in the selection of patients with AH for early LT or in guiding risk‐based interventions post‐LT.
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