Probabilistic analysis is increasing in popularity and importance within engineering and the applied sciences. However, the stochastic perturbation technique is a fairly recent development and ...therefore remains as yet unknown to many students, researchers and engineers. Fields in which the methodology can be applied are widespread, including various branches of engineering, heat transfer and statistical mechanics, reliability assessment and also financial investments or economical prognosis in analytical and computational contexts.Stochastic Perturbation Method in Applied Sciences and Engineeringis devoted to the theoretical aspects and computational implementation of the generalized stochastic perturbation technique. It is based on any order Taylor expansions of random variables and enables for determination of up to fourth order probabilistic moments and characteristics of the physical system response.Key features:Provides a grounding in the basic elements of statistics and probability and reliability engineeringDescribes the Stochastic Finite, Boundary Element and Finite Difference Methods, formulated according to the perturbation method Demonstrates dual computational implementation of the perturbation method with the use of Direct Differentiation Method and the Response Function Method Accompanied by a website (www.wiley.com/go/kaminski) with supporting stochastic numerical softwareCovers the computational implementation of the homogenization method for periodic composites with random and stochastic material propertiesFeatures case studies, numerical examples and practical applicationsStochastic Perturbation Method in Applied Sciences and Engineeringis a comprehensive reference for researchers and engineers, and is an ideal introduction to the subject for postgraduate and graduate students.
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for ...colonoscopy.
This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence.
The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).
While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal ...Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial.
Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up.
The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.
Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct ...reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs). iRECs exhibit epithelial features, a global gene expression profile resembling their native counterparts, functional properties of differentiated renal tubule cells and sensitivity to nephrotoxic substances. Furthermore, iRECs integrate into kidney organoids and form tubules in decellularized kidneys. Our approach demonstrates that reprogramming factors can be identified by targeted in silico analysis. Renal tubular epithelial cells generated ex vivo by forced expression of transcription factors may facilitate disease modelling, drug and nephrotoxicity testing, and regenerative approaches.
Because of the properties of the material (concrete), computer simulations in the field of reinforced concrete structures are pose a challenge. As opposed to steel, concrete when subjected to ...compression exhibits nonlinearity right from the start. Moreover, it much quicker undergoes degradation under tension. All this poses difficulties for numerical analyses. Parameters needed to correctly model concrete under compound stress are described in this paper. The parameters are illustrated using the Concrete Damaged Plasticity model included in the ABAQUS software.
Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear.
We performed a pragmatic, randomized ...trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause.
Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval CI, 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04).
In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).
Summary
A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and ...pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment‐resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti‐ictogenesis, antiepileptogenesis, and/or disease‐modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof‐of‐concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries.
The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs ...subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts.
Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon.
Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy.
The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.
Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%‐20% ...of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease‐modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N‐acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially “repurposable” medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury–treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose–blood level relationship, brain target engagement, and dose‐response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.
Adenoma detection rate and risk of colorectal cancer Wieszczy, P.; Regula, J.; Kaminski, M.F.
Baillière's best practice & research. Clinical gastroenterology,
August 2017, 2017-Aug, 2017-08-00, 20170801, Volume:
31, Issue:
4
Journal Article
Peer reviewed
The aim of this paper was to discuss association between adenoma detection rate (ADR) and interval colorectal cancer risk.
Adenoma detection rate is being used as a benchmark quality measure for ...colonoscopy. There are three studies showing inverse association between ADR and interval colorectal cancer risk. One recent study reports significant impact of increased ADR on decreasing interval colorectal cancer risk.
We discussed evidence for using ADR as a quality measures in colonoscopy and flexible sigmoidoscopy. We revised three studies (Kaminski et al., N Engl J Med 2010; Corley et al., N Engl J Med 2014 and Rogal et al., Clin Gastroenterol Hepatol, 2013) analyzing association between ADR and interval colorectal cancer. We collated strengths and weaknesses of these studies with the perspective of clinical impact of their results.
Kaminski et al. and Corley et al. reported inverse association between ADR at colonoscopy and interval colorectal cancer. Kaminski et al. showed that patients examined by endoscopists with ADR of less than 20% had over 10 times greater risk of interval colorectal cancer during the follow-up time than those examined by endoscopists with ADR ≥20%. Additionally, Corley et al. showed that ADR ≥28% resulted in a significantly lower risk of colorectal cancer death than ADR of less than 19%. In parallel, Rogal et al. reported similar association for flexible sigmoidoscopy, with 2.4 higher odds of interval colorectal cancer diagnosis during follow-up time in patients examined by endoscopists with distal ADR <7.2% than those with distal ADR ≥7.2%.
Apart from inevitable clinical importance of the studies, they are not without disadvantages. In Kaminski et al. study cohort and study endpoint are well defined, but there is lack of statistical power to provide more robust results. In Rogal et al. study cohort is well defined, but approximation of the study endpoint was used. Finally, Corley et al. study has both poorly defined study cohort and study endpoint, but has the highest statistical power of all three to detect the differences for both interval colorectal cancer and colorectal cancer death.
Both, inverse relationship between ADR and ADR improvement and colorectal cancer risk and death reaffirm ADR as a crucial quality control parameter.
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