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The false discovery rate (FDR) measures the proportion of false discoveries among a set of hypothesis tests called significant. This quantity is typically estimated based on p-values or test statistics. In some scenarios, there is additional information available that may be used to more accurately estimate the FDR. We develop a new framework for formulating and estimating FDRs and q-values when an additional piece of information, which we call an "informative variable", is available. For a given test, the informative variable provides information about the prior probability a null hypothesis is true or the power of that particular test. The FDR is then treated as a function of this informative variable. We consider two applications in genomics. Our first application is a genetics of gene expression (eQTL) experiment in yeast where every genetic marker and gene expression trait pair are tested for associations. The informative variable in this case is the distance between each genetic marker and gene. Our second application is to detect differentially expressed genes in an RNA-seq study carried out in mice. The informative variable in this study is the per-gene read depth. The framework we develop is quite general, and it should be useful in a broad range of scientific applications.
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Marcadores Genéticos , Genômica , Animais , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Genômica/métodos , Camundongos , Probabilidade , Saccharomyces cerevisiae/genéticaRESUMO
WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to systematically assess drug therapy in the guidelines for inflammatory bowel disease and to provide recommendations for the development of such guidelines. STUDY DESIGN: A systematic search was conducted in databases and on websites to identify guidelines for the treatment of inflammatory bowel disease. Qualified guidelines were assessed through the Appraisal of Guidelines for Research and Evaluation (AGREE II). Evidence from the guidelines was extracted from the guidelines themselves. The Oxford Centre for Evidence-based Medicine (OCEBM) evidence grading system was used to regrade and assess this evidence. RESULTS: A total of 11 guidelines for the medical treatment of inflammatory bowel disease (Crohn's disease and ulcerative colitis) (2015-2019) were finally included, and after scoring using the AGREE II tool, the median scores in each domain were as follows: â . scope and purpose (median score=88.9%, range: 76.4%-91.7%), â ¡. stakeholder involvement (median =38.9%, range: 18.1%-61.1%), â ¢. rigour of development (median =69.3%, range: 39.6%-77.6%), â £. clarity and presentation (median =97.2%, range: 91.7%-100%), â ¤. applicability (median =45.8%, range: 24%-68.8%) and â ¥. editorial independence (median =94.0%, range: 0-100%). Most of the guidelines scored over 60%, which is worthy of clinical recommendation, but different guidelines suggest that there is a great difference in drug therapy, mainly due to various populations, diverse focuses of attention, distinct efficacy of drugs between Crohn's disease and ulcerative colitis, and the preference of guiding developers for select evidence. WHAT IS NEW AND CONCLUSION: The quality of medical treatment guidelines for inflammatory bowel disease varies considerably. Over the past 5 years, medical treatment has been heterogeneous among different guidelines. Consideration of factors leading to heterogeneity of recommendations for drug treatment, especially preferences for evidence selection, will help upgrade the guidelines.
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Doenças Inflamatórias Intestinais/tratamento farmacológico , Guias de Prática Clínica como Assunto , Corticosteroides/uso terapêutico , Ácidos Aminossalicílicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/fisiopatologiaRESUMO
OBJECTIVE: The management of the hernia sac is the core step of laparoscopic indirect inguinal hernioplasty. In this study, a randomized controlled trial was conducted to evaluate the clinical effect of laparoscopic total extraperitoneal inguinal herniorrhaphy (TEP) with hernia sac transection and complete sac reduction. METHOD: From May 2017 to May 2018, 70 patients aged 18-75 with primary indirect inguinal hernia in our hospital were randomly divided into a transected sac group (TS) and a completely reduced sac group (RS). The primary outcomes compared between the two groups were the hernia sac treatment time, operation time, and the incidence of seroma formation after operation. Secondary outcomes included acute pain, chronic pain (pain which lasted for at least 3 months), hospital stay, recurrence rate, and other complications. RESULT: There were no significant differences in baseline demographic characteristics including age, sex, hernia type, size of hernia defect, and follow-up time between the two groups. The times required for hernia sac separation and operation in the TS group were significantly shorter than in the control group (6.1 ± 2.3 vs. 25 ± 5.8 min for hernia sac separation, p < 0.01; and 35.10 ± 3.50 vs. 54.40 ± 4.20 min for operation, p < 0.01). There was no significant difference in hospitalization time, incidence of acute pain, seroma formation, or urinary retention between the two groups. During the 12-month follow-up period, chronic pain, early recurrence, and other complications were not found in either group. CONCLUSION: Both the hernia sac transection technique and the complete sac reduction technique are safe and reliable. The hernia sac transection technique is a simple and effective hernia sac treatment method. It reduces the operation time and does not increase seroma or acute or chronic pain. It is valuable and likely to be popularly applied.
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Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Adolescente , Adulto , Idoso , Feminino , Herniorrafia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Seroma/etiologia , Adulto JovemRESUMO
For multiple testing based on discrete p-values, we propose a false discovery rate (FDR) procedure "BH+" with proven conservativeness. BH+ is at least as powerful as the BH (i.e., Benjamini-Hochberg) procedure when they are applied to superuniform p-values. Further, when applied to mid-p-values, BH+ can be more powerful than it is applied to conventional p-values. An easily verifiable necessary and sufficient condition for this is provided. BH+ is perhaps the first conservative FDR procedure applicable to mid-p-values and to p-values with general distributions. It is applied to multiple testing based on discrete p-values in a methylation study, an HIV study and a clinical safety study, where it makes considerably more discoveries than the BH procedure. In addition, we propose an adaptive version of the BH+ procedure, prove its conservativeness under certain conditions, and provide evidence on its excellent performance via simulation studies.
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Biometria/métodos , Reações Falso-PositivasRESUMO
Multiple testing (MT) with false discovery rate (FDR) control has been widely conducted in the "discrete paradigm" where p-values have discrete and heterogeneous null distributions. However, in this scenario existing FDR procedures often lose some power and may yield unreliable inference, and for this scenario there does not seem to be an FDR procedure that partitions hypotheses into groups, employs data-adaptive weights and is nonasymptotically conservative. We propose a weighted p-value-based FDR procedure, "weighted FDR (wFDR) procedure" for short, for MT in the discrete paradigm that efficiently adapts to both heterogeneity and discreteness of p-value distributions. We theoretically justify the nonasymptotic conservativeness of the wFDR procedure under independence, and show via simulation studies that, for MT based on p-values of binomial test or Fisher's exact test, it is more powerful than six other procedures. The wFDR procedure is applied to two examples based on discrete data, a drug safety study, and a differential methylation study, where it makes more discoveries than two existing methods.
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Biometria , Modelos Estatísticos , Simulação por Computador , Metilação , Preparações FarmacêuticasRESUMO
BACKGROUND: Inferior epigastric vascular anatomical landmarks for anterior inguinal hernia repair is an alternative surgical procedure. We present our experience and outcome of the way. METHODS: We performed a retrospective analysis of 230 patients who received anterior tension-free hernia repair between May 2016 to May 2017. Among these cases, 120 were performed using the traditional transinguinal preperitoneal (TTIPP) technique while 100 were performed using the vascular anatomic landmark transinguinal preperitoneal (VALTIPP) technique. Between these two groups, we compared the operation time, length of hospital stay, complication rates, and the visual analog scale (VAS) for pain at 2 days, 3 months, and 6 months after surgery. RESULTS: Surgery was well-tolerated in both groups with no significant hemorrhage or complications. The operation times for the VALTIPP and TTIPP groups were 42.52 ± 9.15 and 53.84 ± 10.64 min (P < 0.05), respectively. Ten patients in the VALTIPP group and 17 patients in the TTIPP group reported sensations of foreign bodies (P < 0.05). The VAS pain score in VALTIPP patients at 2 days (4.0 ± 0.5), 3 months (1.0 ± 0.3), and 6 months (0.9 ± 0.3) were significantly lower when compared with those of TTIPP patients (5.3 ± 0.9 at 2 days, 1.8 ± 0.4 at 3 months, and 1.1 ± 0.1 at 6 months, p < 0.05). No statistically significant differences were found in age, gender, BMI, hernia type and location, follow-up period, incidence of post-operative seromas, recurrence rate, or length of hospital stay. CONCLUSION: Anterior inguinal hernia repair using inferior epigastric vascular anatomical landmarks may lead to reduced operation times, reduced sensations of foreign bodies, and reduced post-operative pain. This technique is simple, practical, and effective in the management of inguinal hernias.
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Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória/epidemiologia , Recidiva , Estudos Retrospectivos , Seroma/epidemiologiaRESUMO
We consider multiple testing with false discovery rate (FDR) control when p values have discrete and heterogeneous null distributions. We propose a new estimator of the proportion of true null hypotheses and demonstrate that it is less upwardly biased than Storey's estimator and two other estimators. The new estimator induces two adaptive procedures, that is, an adaptive Benjamini-Hochberg (BH) procedure and an adaptive Benjamini-Hochberg-Heyse (BHH) procedure. We prove that the adaptive BH (aBH) procedure is conservative nonasymptotically. Through simulation studies, we show that these procedures are usually more powerful than their nonadaptive counterparts and that the adaptive BHH procedure is usually more powerful than the aBH procedure and a procedure based on randomized p-value. The adaptive procedures are applied to a study of HIV vaccine efficacy, where they identify more differentially polymorphic positions than the BH procedure at the same FDR level.
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Biometria/métodos , Reações Falso-PositivasRESUMO
This study evaluated the efficacy of hyperspectral imaging (HSI) for the rapid identification of pathogens in dairy products at the colony and cellular levels. The colony and cellular levels studies were designed as completely randomized with six replications. Three strains of Listeria monocytogenes, four strains of Escherichia coli O157: H7, Big Six Shiga toxin-producing E. coli, three strains of Staphylococcus aureus, and ten serovars of Salmonella were used in this study. Pure cultures were streaked for isolation on respective selective media, and hyperspectral data (400-1100 nm wavelength) at the colony and cellular levels were collected and stored as reference libraries. Whole milk and whole milk powder were artificially inoculated (<10 CFU/g or mL) with individual pathogenic strains/serovars. All milk and milk powder samples were enriched using brain heart infusion (BHI) broth at 37°C for 24 h, streaked for isolation on the respective selective media, and hyperspectral data for individual pathogenic strains/serovars at the colony and cellular levels were acquired and treated as test samples data. The acquired colony or cellular images were imported into ENVI software and three regions of interest were selected for each image to obtain hyperspectral data for reference libraries and test samples. Using the kNN classifier and cross-validation technique, overall classification accuracies of 90.38% and 34% were obtained for the colony- and cellular-level identification, respectively. The individual classification accuracies of pathogens in dairy products at the colony level varied between 77.5% to 100%, whereas the accuracy varied between 2.78% and 49.17% for the cellular level.
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The objective of this foundational study was to develop and evaluate the efficacy of an affordable hyperspectral imaging (HSI) system to identify single and mixed strains of foodborne pathogens in dairy products. This study was designed as a completely randomized design with three replications. Three strains each of Escherichia coli O157:H7 and Listeria monocytogenes were evaluated either as single or mixed strains with the HSI system in growth media and selected dairy products (whole milk, and cottage and cheddar cheeses). Test samples from freshly prepared single or mixed strains of pathogens in growth media or inoculated dairy products were streaked onto selective media (PALCAM and/or Sorbitol MacConkey agar) for isolation. An isolated colony was selected and mixed with 1 ml of HPLC grade water, vortexed for 1 min, and spread over a microscope slide. Images were captured at 2000× magnification on the built HSI system at wavelengths ranging from 400 nm to 1100 nm with 5-nm band intervals. For each image, three cells were selected as regions of interest (ROIs) to obtain hyperspectral signatures of respective bacteria. Reference pathogen libraries were created using growth media, and then test pathogenic cells were classified by their hyperspectral signatures as either L. monocytogenes or E. coli O157:H7 using k-nearest neighbor (kNN) and cross-validation technique in R-software. With the implementation of kNN (k = 3), overall classification accuracies of 58.97% and 61.53% were obtained for E. coli O157:H7 and L. monocytogenes, respectively.
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BACKGROUND: The aim of the study was to conduct a systematic review to comprehensively evaluate the relationship between pistachio intake and obesity. METHODS: We searched 6 databases and acquired parameters from randomized controlled trials regarding obesity, including body weight, body mass index (BMI), and waist circumference. A fixed-effect model was applied to the meta-analysis for the weighted mean difference (WMD) between a diet with pistachios and a control diet. RESULTS: Eleven trials including a total of 1593 subjects met the inclusion criteria. Compared to the group on a control diet, the pistachio diet group showed lower BMI values (WMD: -0.18âkg/m; 95% confidence interval [CI]: -0.26, -0.11âkg/m; Iâ=â29.8%) and no differences in body weight (WMD: -0.22âkg; 95% CI: -0.50, 0.07âkg; Iâ=â0.0%) or waist circumference (WMD: 0.76âcm; 95% CI: -0.11, 1.63âcm; Iâ=â7.0%). CONCLUSION: A diet with pistachios reduced BMI and had no significant effects on body weight and waist circumference.
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Adiposidade , Dieta , Nozes , Obesidade/prevenção & controle , Pistacia , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The mechanism of early oral nutrition that regulates the mast cell-nerve axis to improve postoperative ileus (POI) remains unclear. This study aims to investigate whether early oral nutrition can improve POI through Transient receptor potential ankyrin-1 (TRPA1)/cholecystokinin 1 receptor (CCK1-R) in the mast cell-nerve axis. METHODS: Experiment 1: Male Sprague-Dawley (SD) rats were randomly divided into the TRPA1 inhibitor + oral nutrition group (TI + ON + POI), oral nutrition group (ON + POI), POI group (POI) and sham surgery group (Sham). Nine rats in each group were treated. Experiment 2: Primary cultures of mast cells and dorsal root ganglion cells were created, and a non-contact co-culture system was established. The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. The results of expression of TRPA1, CCK1-R and histamine in colon tissue, portal vein blood, supernatant or dorsal root ganglia, intestinal transport test and mast cell morphology were analysed. RESULTS: In experiment 1, Early oral nutrition could alleviate the degranulation and activation of mast cells and alleviate the inflammatory reaction of intestinal wall muscles (P<0.05). Early oral nutrition improved POI by stabilizing mast cells with TRPA1. TRPA1 inhibitor decreased CCK1-R concentrations in portal vein blood and CCK1-R expression in colonic smooth muscle (P<0.05). In experiment 2, the change in mast cell function regulated the secretion of CCK1-R by neurons, CCK1-R negatively regulated the degranulation and activation of mast cells (P<0.05), and mast cells positively regulated the expression of TRPA1 protein in DRG (P<0.05). CONCLUSIONS: Early enteral nutrition can improve POI through the TRPA1/CCK1-R-mediated mast cell-nerve axis. TRPA1 positively regulates CCK1-R to stabilize mast cells, but TRPA1 is not the target of the downstream CCK1-R pathway.
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OBJECTIVES: The aim of this study was to systematically assess the nutrition care procedures in nutrition guidelines for cancer patients and identify gaps limiting evidence-based practise. METHODS: A systematic search of databases and websites was conducted to identify nutrition guidelines for cancer patients. The quality of the eligible guidelines was evaluated by using the Appraisal of Guidelines for Research and Evaluation (AGREE II). The Measurement Scale of Rate of Agreement (MSRA) was used to assess the scientific agreement of formulated recommendations for nutrition care procedures in the guidelines (2017-2019), and evidence supporting these recommendations was extracted and analysed. RESULTS: Seventeen nutrition guidelines for cancer patients were identified. Only European Society for Clinical Nutrition and Metabolism (ESPEN) and Australian guidelines have a total quality score of more than 60%, which is worthy of clinical recommendation. Twelve guidelines (2017-2019) were included to further analyse the heterogeneity and causes of nutrition care procedures, and we found that the content and tools of nutrition screening and assessment, the application of immune nutrients, and the selection of nutritional support pathways were heterogeneous. The main reasons for the heterogeneity of nutrition care procedures were insufficient attention to nutrition risk screening, differences in recommendations for nutrition assessment, immune nutrients and nutritional support, unreasonable citation of screening and assessment evidence, preference of developers, and lack of evidence of high-quality research on energy and nitrogen demand. In addition, the fairness and propensity of the guidelines for the selection of evidence for different cancer patients are also potential reasons for the heterogeneity of nutritional care procedures. CONCLUSIONS: The quality of the nutrition guidelines for cancer patients was highly variable. The nutrition care procedures were heterogeneous among the different guidelines in the last 3 years. Specific improvement of the factors leading to the heterogeneity of nutrition care procedures will be a reasonable and effective way for developers to upgrade the nutrition care procedures in the guidelines for cancer patients.
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Disparidades em Assistência à Saúde/normas , Desnutrição/dietoterapia , Neoplasias/dietoterapia , Avaliação Nutricional , Terapia Nutricional/normas , Estado Nutricional , Guias de Prática Clínica como Assunto/normas , Lacunas da Prática Profissional/normas , Consenso , Humanos , Desnutrição/diagnóstico , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/fisiopatologia , Terapia Nutricional/efeitos adversosRESUMO
INTRODUCTION: The occurrence of perineal fistula is a significant evesnt in the evolution of Crohn's disease. Approximately 21% to 23% of patients develop perineal fistula at least once in their lifetime, approximately 30% of patients have cases of recurrence, and the refractory and recurrent perineal lesions of Crohn's disease impose a great economic burden on patients. The main purpose of this review was to investigate the quality of guidelines for perineal fistula in Crohn's disease. AREA COVERED: Relevant websites and databases were systematically searched to identify and select clinical guidelines related to perineal fistulas in Crohn's disease. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and used intraclass correlation coefficients (ICC) to measure the agreement among the guideline reviewers. CONCLUSION: There is much room for improvement in the quality of guidelines for the management of perineal fistulas in Crohn's disease. The recommendations and evidence for guidelines for the management of perineal fistulas in Crohn's disease are quite heterogeneous, and guideline-developers would be well advised to address the above issues during future guideline development.
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Doença de Crohn , Fístula Retal/terapia , Doença de Crohn/complicações , Humanos , Guias de Prática Clínica como Assunto , Fístula Retal/etiologiaRESUMO
PURPOSE: To investigate the role of percutaneous transhepatic cholangial drainage (PTCD) combined with percutaneous endoscopic jejunostomy (PEJ) in maintaining the nutrition state in patients with advanced ampullary neoplasms. MATERIALS AND METHODS: Sixty patients who suffered from advanced ampullary neoplasms and could not tolerate internal drainage operation or biliary stent placement were enrolled. After PTCD, PEJ was implemented, and then the enteral nutrient solution + bile were instilled through PEJ tube for enteral nutrition support. Before and 1, 2, 3, and 4 weeks after surgery, the body weight, bilirubin, liver function, nutritional status, and immunologic function indexes were detected and compared. RESULTS: All patients had successfully completed PTCD combined with PEJ, and no serious complication occurred. The body mass index of the patients from 4 weeks after surgery was significantly higher than before (P < 0.05). From 2 weeks, both serum total bilirubin and direct bilirubin levels were significantly lower than before (P < 0.05). From 1 week, both alanine aminotransferase and aspartate aminotransferase levels were significantly lower than before (P < 0.05); from 2 weeks, the level of gamma-glutamyl transferase was significantly lower than before (P < 0.05). From 1 week, the levels of albumin, transferrin, and prealbumin were significantly increased compared with before (P < 0.05), and serum CD3+ cell content, CD4+ cell content, and CD4+/CD8+ ratio were significantly improved compared with before (P < 0.05). CONCLUSION: PTCD combined with PEJ is a safe and effective method for maintaining nutrition state in patients with advanced ampullary neoplasms.