Wilkersonalbrektsen5735

Replicability of results is regarded as the corner stone of science. Recent research seems to raise doubts about whether this requirement is generally fulfilled. Often, replicability of results is defined as repeating a statistically significant result. However, since significance may not imply scientific relevance, dual-criterion study designs that take both aspects into account have been proposed and investigated during the last decade. Originally developed for proof-of-concept trials, the design could be appropriate for phase III trials as well. In fact, a dual-criterion design has been requested for COVID-19 vaccine applications by major health authorities. Sunitinib In this article, replicability of dual-criterion designs is investigated. It turns out that the probability to replicate a significant and relevant result can become as low as 0.5. The replication probability increases if the effect estimator exceeds the minimum relevant effect in the original study by an extra amount.The tailings spilled by the Fundão Dam rupture in the Doce River basin (Brazil) had a high pH, elevated sodium (Na) and ether amine, and low soil organic matter. With the aim of decreasing the toxic compounds, we established 2 remediation strategies treatment 1, phytoremediation with tolerant native species of the Atlantic Forest cultivated on scraped sediment plus the incorporation of organic matter; and treatment 2, phytoremediation with native species plus superficial deposition of organic matter. The experimental site was compared with a degraded site that the dam tailings had reached and with a preserved site, a fragment of preserved Atlantic Forest. After 12 mo, plants showed an outstanding growth, especially after treatment 1 (~4 m), and the remediation procedures resulted in significant decreases in pH (from 8.0 to ~6.0), Na (from 154 to 22-35 mg/kg), electrical conductivity, and ether amine (from 6.0 to 0.5 mg/kg) in both treatments. By contrast, ammonium, a product of ether amine degradation, showed a significant increase in the experimental site, along with a significant increase in nitrate and improvement of soil microbial populations assessed by phospholipid fatty acid analysis. The treatments also improved soil fertility in the experimental site, as estimated by soil nutrients, cation exchange capacity, and soil aggregation. Based on the parameters analyzed, a principal component analysis showed that samples from the degraded site and the preserved site clustered in an opposite position and those from the experimental site clustered in an intermediate position but closer to the samples from the preserved site. Overall, our results demonstrated that the remediation procedures adopted were effective and resulted in the rehabilitation of a riparian forest over dam tailings contaminated with Na and ether amine. Environ Toxicol Chem 2021;001-15. © 2021 SETAC.Proteins that recognize the epigenetic modifications function as mediators to interpret the epigenetic codes. Hypoxia response and metabolic rewiring are two major events during cancer progression. However, it's still unclear whether and how epigenetic regulator integrates hypoxia response and metabolism together. We data mined the clinical association of 33 histone Kac reader proteins with liver cancer and that AF9 is upregulated in cancer and correlates with tumor stage and poor prognosis. Conditional deletion of Af9 in mouse liver resulted in decreased tumor formation induced by c-Met/β-catenin. Loss of AF9 heavily impaired cell proliferation and completely blocked solid tumor formation. We further discovered AF9 formed a positive feedback circuit with HIF1α and also stabilized cMyc. Mechanically, AF9 interacted with HIF1α and targeted HIF1A promoter while AF9 recognized cMyc acetylation at K148, protected cMyc phosphorylation at S62 and then stabilized the cMyc which in turn upregulates PFKP expression. Otherwise, knockout of Af9 in mouse hepatocyte increased the infiltration of CD8+ T cells which is linked to the downregulation of LDHA. In conclusions, AF9 is upregulated to promote gene expression of hypoxia tolerance and glycolysis by simultaneously forming a complex with HIF1α and recognizing acetylated cMyc. Our results establish the oncogenic role of AF9 in human liver cancer, which could be a potential target for designing novel drugs against liver cancer.Promotion time cure rate models (PCM) are often used to model the survival data with a cure fraction. Medical images or biomarkers derived from medical images can be the key predictors in survival models. However, incorporating images in the PCM is challenging using traditional nonparametric methods such as splines. We propose to use neural network to model the nonparametric or unstructured predictors' effect in the PCM context. Expectation-maximization algorithm with neural network for the M-step is used for parameter estimation. Asymptotic properties of the proposed estimates are derived. Simulation studies show good performance in terms of both prediction and estimation. We finally apply our methods to analyze the brain images from open access series of imaging studies data.Identifying a therapist with expertise in treating eating disorders (EDs) can be a daunting process for a consumer, resulting in delayed access to evidence-based treatment, prolonging unnecessary suffering. We developed a consumer checklist designed to empower consumers to locate evidence-based treatment earlier. We co-designed (researchers and people with lived experience of an ED) a 15-item consumer checklist, for use in a meeting with a potential therapist. A survey about the checklist was sent out to people with lived experience and clinicians, seeking quantitative endorsement of each item's helpfulness in the checklist, and inviting qualitative feedback. Seventeen people with lived experience and 11 clinicians gave feedback. The items were rated as being helpful, with overlap between the two groups as to the most helpful items. Both groups rated the checklist as likely to help locate effective treatment earlier. The checklist forms a basis for a useful consumer tool in their treatment journey. Examination of its uptake and impact on outcomes for consumers seeking treatment is recommended.This study describes the direct synthesis of 2-amino-4-(phenylsubstituted)-5H-indeno[1,2-b]pyridine-3-carbonitrile derivatives 5-21, through sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-indanone in the presence of ammonium acetate and acetic acid (catalytic). The biological study showed that compound 10 significantly impeded proliferation of the cell lines PC-3, LNCaP, and MatLyLu. The antimetastatic effects of compound 10 could be related with inhibition of MMP9 in the PC-3 and LNCaP human cell lines. On the basis of a study of the structure-activity relationship of these compounds, we propose that the presence of two methoxy groups at positions 6 and 7 of the indeno nucleus and a 4-hydroxy-3-methoxy phenyl substitution pattern at position 4 of the pyridine ring is decisive for these types of molecules to exert very good antiproliferative and antimetastatic activities.Floods occur frequently and cause considerable damage to local environments. Effectively assessing the flood risk contributes to reducing loss caused by such disasters. In this study, the weighted naïve Bayes (WNB) method was selected to evaluate flood risk, and the entropy weight method was employed to compute the weights. A sampling and verifying model was employed to generate the most accurate conditional probability table (MACPT) to calculate the probability of flooding. When using the framework integrating WNB with the sampling and verifying model, previous studies could not obtain a WNB-based MACPT and the WNB classification accuracy, for lacking WNB functions that could be called directly. Facing this issue, in this study we developed WNB functions with the MATLAB platform to directly integrate with the sampling and verifying model to generate a WNB-based MACPT, contributing to the greater interpretability and extensibility of the model. Shantou and Jieyang cities in China were selected as the study area. The results demonstrate that (1) a WNB-based MACPT can reflect the real spatial distribution of flood risk and (2) the WNB outperform the NB when integrated with the sampling and verifying model. The resulting gridded estimation reveal a detailed spatial pattern of flood risk, which can serve as a realistic reference for decision making related to floods. Furthermore, the proposed method uses less data, which would be helpful in developing countries where long-term intensive hydrologic monitoring is limited.Randomized vaccine trials are used to assess vaccine efficacy (VE) and to characterize the durability of vaccine-induced protection. If efficacy is demonstrated, the treatment of placebo volunteers becomes an issue. For COVID-19 vaccine trials, there is broad consensus that placebo volunteers should be offered a vaccine once efficacy has been established. This will likely lead to most placebo volunteers crossing over to the vaccine arm, thus complicating the assessment of long term durability. We show how to analyze durability following placebo crossover and demonstrate that the VE profile that would be observed in a placebo controlled trial is recoverable in a trial with placebo crossover. This result holds no matter when the crossover occurs and with no assumptions about the form of the efficacy profile. We only require that the VE profile applies to the newly vaccinated irrespective of the timing of vaccination. We develop different methods to estimate efficacy within the context of a proportional hazards regression model and explore via simulation the implications of placebo crossover for estimation of VE under different efficacy dynamics and study designs. We apply our methods to simulated COVID-19 vaccine trials with durable and waning VE and a total follow-up of 2 years.A novel and sensitive heart-cutting two-dimensional liquid chromatography with ultraviolet detection method (2D-LC-UV) was developed and validated for determination of amisulpride in human plasma. The 2D-LC system consists of a first dimensional (1 D) LC column and a middle transfer column as well as a second-dimensional (2 D) LC column. After simple protein precipitation, the sample was directly injected into the introduction valve of the 2D-LC system. The 1 D column, playing a role of primary separation and preconcentration for complex plasma matrices, transferred the targets to the intermediate column. Following capture of targets on the middle column online, the analytes were transferred to the 2 D separation column by a six-port valve. The 2 D column, avoiding interference from the plasma matrix, completed further separation and quantification. An assistant pump was optimized for primary enrichment as well as final elution in the heart-cutting mode. The analytical time of amisulpride was 7.401 min. The accuracy was between 0.48 and 8.49%, while the intra- and inter-day precisions ranged from 0.9 to 3.1% and from 1.7% to 3.3%, respectively. The linear range of amisulpride was 48.15-2,407.59 ng/ml, while the extraction recovery was 98.7-101.3%. The strategy established in the study, which was successfully applied to therapeutic drug monitoring of amisulpride for routine clinical detection, displays high sensitivity, good repeatability, convenience and low cost.