parameter optimization
Dotaz
Zobrazit nápovědu
VIII, 219 s. : il. ; 28 cm
In comparison with analytical tools, bioassays provide higher sensitivity and more complex evaluation of environmental samples and are indispensable tools for monitoring increasing in anthropogenic pollution. Nevertheless, the disadvantage in cellular assays stems from the material variability used within the assays, and an interlaboratory adaptation does not usually lead to satisfactory test sensitivities. The aim of this study was to evaluate the influence of material variability on CXCL12 secretion by T47D cells, the outcome of the CXCL-test (estrogenic activity assay). For this purpose, the cell line sources, sera suppliers, experimental and seeding media, and the amount of cell/well were tested. The multivariable linear model (MLM), employed as an innovative approach in this field for parameter evaluation, identified that all the tested parameters had significant effects. Knowledge of the contributions of each parameter has permitted step-by-step optimization. The most beneficial approach was seeding 20,000 cells/well directly in treatment medium and using DMEM for the treatment. Great differences in both basal and maximal cytokine secretions among the three tested cell lines and different impacts of each serum were also observed. Altogether, both these biologically based and highly variable inputs were additionally assessed by MLM and a subsequent two-step evaluation, which revealed a lower variability and satisfactory reproducibility of the test. This analysis showed that not only parameter and procedure optimization but also the evaluation methodology must be considered from the perspective of interlaboratory method adaptation. This overall methodology could be applied to all bioanalytical methods for fast multiparameter and accurate analysis.
Continuous tablet manufacturing is a competitive option to replace the traditional batch manufacturing approach. The aim of this study was to evaluate technology transfer from batch-based direct compression of a commercial tablet formulation to continuous direct compression without changes to the composition of the formulation. Some powder studies were conducted with the raw materials and multi-tip punches were utilized in the tableting studies. To lower the high level of tablet weight variability that was evident during preliminary tests, a process parameter optimization was performed using an experimental design with different rpm values of force feeder and mixer impeller. By selecting the most appropriate settings of these parameters for the studied product, the weights of the tablets could be controlled adequately to meet the specification criteria. The functionality of the best-performing parameter settings was investigated with a three-hour-long tableting run. The tablets were evaluated with the same quality criteria as the commercial batch-produced tablets, and they passed all the tests performed in this study. Despite the challenging material properties according to the flowability tests, production of tablets with the desired quality was achieved using the original composition with continuous direct compression.
- MeSH
- bisoprolol * MeSH
- farmaceutická technologie * MeSH
- prášky, zásypy, pudry MeSH
- příprava léků MeSH
- tablety MeSH
- tlak MeSH
- Publikační typ
- časopisecké články MeSH
Východisko. Potenciální výhody a rizika nových operačních technik se mohou u jednotlivých pacientů projevit rozdílně. Cílem práce bylo na základě spolehlivé predikce pooperačních komplikací ověřit možnost vytvoření modelu pro optimalizaci operační techniky u souboru pacientů operovaných pro karcinom rekta. Materiál a metody. Do studie byli zařazeni pacienti operováni v průběhu pěti let pro karcinom konečníku laparoskopickou nebo otevřenou technikou. Matematické modely predikce pooperačních komplikací jednotlivých operačních technik byly odvozeny od skórovacího systému Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM). Spolehlivost predikce pro danou techniku byla otestována a pacienti souboru byli analyzováni s ohledem na „vhodnost“ použité operační techniky. Výsledky. Do studie bylo zařazeno 91 pacientů operovaných otevřenou technikou a 67 pacientů operovaných laparoskopicky s výskytem 45 %, resp. 39 % pooperačních komplikací. Z testovaných proměnných byly pro vznik pooperačních komplikací statisticky významné „kardiální příznaky“ a „závažnost operačního výkonu “ pro otevřené operace, „leukocyty“ a „závažnost operačního výkonu“ pro laparoskopické výkony. Modely predikce postavené na těchto proměnných vykázaly statisticky vysokou spolehlivost. V celém souboru by při ideální volbě operační techniky komplikace teoreticky poklesly o 36 %. Závěr. Spolehlivá predikce pooperačních komplikací může být efektivním nástrojem přizpůsobení chirurgické léčby individuálnímu pacientovi.
Background. Potential benefits and risks of new operation techniques can show up differently in the individual patients. The aim of this pilot study was to verify on the basis of reliable prediction of postoperative complications the possibility to create model for optimization of the operation technique in the cohort of patients operated for rectal carcinoma. Material and methods. The study involved patients operated in the course of five years for rectal carcinoma by means of laparoscopic or open technique. The mathematical models of prediction of postoperative complications of individual operative techniques were derived from the Physiological and Operative Severity Score for enUmeration of Mortality and Morbidity scoring system (POSSUM). The reliability of prediction for the given technique was tested and the patients of the cohort were analyzed with regard to the “suitability” of the operation technique used. Results. The study involved 91 patients operated using open technique and 67 patients operated laparoscopically with the occurrence of 45% and 39% of the postoperative complications respectively. The statistically relevant variables tested for the occurrence of postoperative complications were the “cardiac symptoms” and “severity of the surgery” for open operations, and “leukocytes” and “severity of the surgery” for the laparoscopic operations. The prediction models based on these variables showed statistically high reliability. The complications in the entire cohort would in case of ideal selection of surgical technique drop by 36%. Conclusion. Reliable prediction of the postoperative complications can be potentially effective tool to optimize surgical treatment for an individual patient.
Srdeční resynchronizační terapie (CRT) zlepšuje kvalitu života a/nebo hemodynamické parametry jen u dvou třetin pacientů s biventrikulárním kardiostimulátorem naimplantovaným pro srdeční selhání. U ostatních pacientů (nonrespondérů) se provádí další jemnější programace kardiostimulačních parametrů. Tato optimalizace atrioventrikulárního a ventrikulo‑ventrikulárního zpoždění (AVD a VVD) může zlepšit výkon srdce u části z nich. Efekt AVD a VVD programace se nejčastěji hodnotí pomocí echokardiografických veličin (charakter plnění levé komory, délka diastolické fáze, tepový objem/srdeční výdej, ejekční frakce, LV dP/dT, synchronie kontrakce levé komory pomocí tissue Doppler nebo speckle trackingu). Zatímco všechny tyto parametry prokázaly bezprostřední efekt AVD/VVD optimalizace ve vybraných souborech CRT pacientů, dlouhodobý benefit optimalizace se nepodařilo prokázat randomizovanými studiemi ani metaanalýzou. Článek popisuje současný teoretický koncept optimalizace, metodologické problémy a nevyřešené otázky a dostupnou důkazní literaturu. Možnosti optimalizace jsou shrnuty v současných odborných guidelines, doporučuje se však individuální přístup.
Cardiac resynchronization therapy (CRT) improves the quality of life and/or haemodynamic parameters only in 2/3 of heart failure patients with a biventricular pacemaker implanted. In the rest of these patients (non‑responders), further refinement of pacing parameters is provided. This atrioventricular delay (AVD) and ventriculoventricular delay (VVD) optimization may help to improve cardiac performance in some of them. Echocardiography is widely used to assess the effect of AVD and VVD programming. The diastolic filling pattern, the length of the diastole, stroke volume/cardiac output, ejection fraction, LV dP/dT and LV contraction synchrony by tissue Doppler or speckle tracking are the most frequent criteria used for optimization. Whilst all these variables are proved to demonstrate an instant effect of AVD/VVD optimization in selected groups of CRT patients, neither a randomized study nor a meta‑analysis showed any long‑term benefit in the CRT population. This article describes the theoretical concept of optimization, certain methodological problems and unresolved issues in CRT optimization and evidence in literature already published. Optimization options are summarized in current guidelines but an individual approach is recommended in non‑responders.
- MeSH
- diastola fyziologie MeSH
- echokardiografie metody MeSH
- hemodynamika MeSH
- kardiostimulace umělá metody MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- medicína založená na důkazech MeSH
- srdeční arytmie patofyziologie MeSH
- srdeční komory patofyziologie MeSH
- srdeční resynchronizační terapie * metody MeSH
- srdeční selhání terapie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: High-throughput bioinformatics analyses of next generation sequencing (NGS) data often require challenging pipeline optimization. The key problem is choosing appropriate tools and selecting the best parameters for optimal precision and recall. RESULTS: Here we introduce ToTem, a tool for automated pipeline optimization. ToTem is a stand-alone web application with a comprehensive graphical user interface (GUI). ToTem is written in Java and PHP with an underlying connection to a MySQL database. Its primary role is to automatically generate, execute and benchmark different variant calling pipeline settings. Our tool allows an analysis to be started from any level of the process and with the possibility of plugging almost any tool or code. To prevent an over-fitting of pipeline parameters, ToTem ensures the reproducibility of these by using cross validation techniques that penalize the final precision, recall and F-measure. The results are interpreted as interactive graphs and tables allowing an optimal pipeline to be selected, based on the user's priorities. Using ToTem, we were able to optimize somatic variant calling from ultra-deep targeted gene sequencing (TGS) data and germline variant detection in whole genome sequencing (WGS) data. CONCLUSIONS: ToTem is a tool for automated pipeline optimization which is freely available as a web application at https://totem.software .
In silico methods like molecular docking and pharmacophore modeling are established strategies in lead identification. Their successful application for finding new active molecules for a target is reported by a plethora of studies. However, once a potential lead is identified, lead optimization, with the focus on improving potency, selectivity, or pharmacokinetic parameters of a parent compound, is a much more complex task. Even though in silico molecular modeling methods could contribute a lot of time and cost-saving by rationally filtering synthetic optimization options, they are employed less widely in this stage of research. In this review, we highlight studies that have successfully used computer-aided SAR analysis in lead optimization and want to showcase sound methodology and easily accessible in silico tools for this purpose.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cíl práce: Individuální optimalizace antimikrobiální terapie amoxicilín/klavulanátem (AMC) u nemocných s infekční komplikací syndromu diabetické nohy. Metody: Parmakokinetická analýza individuálních plazmatických koncentrací amoxicilínu v ustáleném stavu při infuzním i perorálním podávání AMC, aplikovaného na základě kvantitativní citlivosti mikrobů. Hodnocení parametrů dynamiky růstu a hynutí modelového kmene Staphylococcus aureus (nejčastějšího původce infekce u nemocných) in vitro. Predikce doby potřebné k poklesu počtu zívych bakterii na 10-6 jako zástupného kritéria účinku terapie a porovnání rychlosti účinku různých dávkových režimů antibiotika podle tohoto kritéria. Výsledky: Na základě individuálních oscilací hladin amoxicilínu v plazmě 17 nemocných s infikovanými ulceracemi při syndromu diabetické nohy a dynamických parametrů modelového mikroba jsme zjistili, že redukce počtu živých bakterií je významně rychleji dosažena při kontinuální i.v. infuzi AMC než při jeho intermitentní infuzi ve stejné denní dávce. Dostatečně rychlý účinek proti vysoce citlivému stafylokoku měla i perorální terapie AMC, ale v nejdéle 8hodinových intervalech. Se snižováním plazmatických koncentrací amoxicilínu docházelo k exponenciálnímu prodlužování doby nezbytné k účinné redukci počtu mikrobů. Závěr: Individuální úprava dávkování AMC podle mikrobiálních dynamických parametrů a dosažených koncentrací antibiotika může urychlit antimikrobiální účinek antibiotika a tím i léčení infekční komplikace u nemocného se syndromem diabetické nohy bez kritické ischemie.
Aim of the study: Individualized optimization of amoxicillin/clavulanate (AMC) antimicrobial therapy in diabetic foot infection. Methods: Pharmacokinetic analysis of individual steady-state plasma amoxicillin concentrations was done both in the i.v. infusion phase and in the oral phase of AMC, administered on the basis of the quantitative susceptibility of the detected microbe(s). The in vitro growth/killing dynamic parameters on model of Staphylococcus aureus as the most frequent isolate were evaluated. Therapeutic protocol optimization, leading to prediction of the earhest time to reduce the number of viable bacteria to 10 -6 as a surrogate criterion of efficacy, was performed. Results: Based on individual plasma amoxicillin oscillations in 17 patients suffering from infected diabetic foot ulcers and the model microbial dynamic parameters, the reduction of the number of viable bacteria was reached significantly earher after the administration of continuous i.v. AMC infusion than after the same daily AMC dose administered intermittently. In case of highly susceptible staphylococcal strain, highly frequent oral therapy of AMC (not longer than 8 hrs dosing interval) was also sufficiently effective. Decreasing plasma amoxicillin concentrations exponentially extended the time required for effective reduction of microbes. Conclusion: Individualized optimization of amoxicillin/clavulanate dosage on the basis of growth/killing microbial dynamic parameters and antibiotic concentration/time fluctuations may enhance the antimicrobial effect and the treatment of infected non-critical ischemic diabetic foot ulcers.
In the early stage of drug development the solubility of drug candidate is the most crucial physicochemical parameter to be defined for the selection of lead compound. Conventional shake flask method of solubility determination has now been replaced with more precise measurements like ultraviolet absorption, nephelometry, nuclear magnetic resonance and potentiometry. The development of a simple, rapid, sensitive and precise spectrophotometric method for the routine quantitative determination of samples will definitely reduce unnecessary tedious sample preparations and the cost of materials and labour. This article accounts for the measurement of solubility limit of few selected drugs by spectrophotometry using dilution technique. This has been done to optimize the method for rapid and convenient determination of drug solubility limit. Concentration of saturated solution of drug was determined from the absorbance versus concentration plots of various diluted solutions of drug as per Beer-Lambert law and was reported as drug solubility limit.
Optical trapping of particles has become a powerful non-mechanical and non-destructive technique for precise particle positioning. The manipulation of particles in the evanescent field of a channel waveguide potentially allows for sorting and trapping of several particles and cells simultaneously. Channel waveguide designs can be further optimized to increase evanescent field prior to the fabrication process. This is crucial in order to make sure that the surface intensity is sufficient for optical trapping. Simulation configurations are explained in detail with specific simulation flow. Discussion on parameters optimization; physical geometry, optical polarization and wavelength is included in this paper. The effect of physical, optical parameters and beam spot size on evanescent field has been thoroughly discussed. These studies will continue toward the development of a novel copper ion-exchanged waveguide as a method of particle sorting, with biological cell propulsion studies presently underway.
- MeSH
- analýza selhání vybavení MeSH
- design s pomocí počítače MeSH
- design vybavení MeSH
- ionty chemie MeSH
- měď chemie MeSH
- optická pinzeta * MeSH
- počítačová simulace MeSH
- povrchová plasmonová rezonance přístrojové vybavení MeSH
- radiační rozptyl MeSH
- světlo MeSH
- teoretické modely * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
