Treatment endpoints in ulcerative colitis:Does one size fit all?

A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Accurate Measurement Method for Tube's Endpoints Based on Machine Vision

Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube＇s endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube＇s endpoints based on machine vision is proposed. First, reflected light on tube＇s surface can be removed by using photometric linearization. Then, based on the optimization model for the tube＇s endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube＇s endpoint are obtained. To confirm the feasibility, ll tubes are processed to remove the reflected light and then the endpoint＇s positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 ram. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube＇s endpoints without any surface treatment or any tools and can realize on line measurement.

Endpoint Prediction of EAF Based on Multiple Support Vector Machines

The endpoint parameters are very important to the process of EAF steel-making, but their on-line measurement is difficult. The soft sensor technology is widely used for the prediction of endpoint parameters. Based on the analysis of the smelting process of EAF and the advantages of support vector machines, a soft sensor model for predicting the endpoint parameters was built using multiple support vector machines （MSVM）. In this model, the input space was divided by subtractive clustering and a sub-model based on LS-SVM was built in each sub-space. To decrease the correlation among the sub-models and to improve the accuracy and robustness of the model, the sub- models were combined by Principal Components Regression. The accuracy of the soft sensor model is perfectly improved. The simulation result demonstrates the practicability and efficiency of the MSVM model for the endpoint prediction of EAF.

Determination of 50% endpoint titer using a simple formula

Two commonly used methods for calculating 50% endpoint using serial dilutions are Spearman-Karber method and Reed and Muench method. To understand/apply the above formulas, moderate statistical/mathematical skills are necessary. In this paper, a simple formula/method for calculating 50% endpoints has been proposed. The formula yields essentially similar results as those of the SpearmanKarber method. The formula has been rigorously evaluated with several samples.

ENDPOINT ESTIMATE FOR MAXIMAL COMMUTATORS WITH NON-DOUBLING MEASUES

The authors establish the weak type endpoint estimate for the maximal commutators generated by Calderon-Zygmund singular integrals and Orlicz type functions with non-doubling measures.

Speech Endpoint Detection in Noisy Environments Using EMD and Teager Energy Operator

Accurate endpoint detection is a necessary capability for speech recognition. A new energy measure method based on the empirical mode decomposition （EMD） algorithm and Teager energy operator （TEO） is proposed to locate endpoint intervals of a speech signal embedded in noise. With the EMD, the noise signals can be decomposed into different numbers of sub-signals called intrinsic mode functions （IMFs）, which is a zero-mean AM-FM component. Then TEO can be used to extract the desired feature of the modulation energy for IMF components. In order to show the effectiveness of the proposed method, examples are presented to show that the new measure is more effective than traditional measures. The present experimental results show that the measure can be used to improve the performance of endpoint detection algorithms and the accuracy of this algorithm is quite satisfactory and acceptable.

Endpoint forecasting on composite regeneration by coupling cerium-based additive and microwave for diesel particulate filter

Numerical simulation has been carried out to investigate the major factors affecting the time of composite regeneration due to coupling cerium-based additive and microwave for diesel particulate f3ilter(DPF). Effect on the composite regeneration time from various factors such as mass flow rate of exhaust gas, temperature of exhaust gas, oxygen concentration of exhaust gas, microwave power and amount of cerium-based additive are investigated. And a mathematical model based on fuzzy least squares support vector machines has been developed to forecast the endpoint of the composite regeneration. The results show that the relative error of endpoint forecasting model of composite regeneration is less than 3.5%, and the oxygen concentration of exhaust gas has the biggest effect on the endpoint of composite regeneration, followed by the mass flow rate of exhaust gas, the microwave power, the temperature of exhaust gas and the amount of cerium-based additive.

Novel method for determination of sodium in foods by thermometric endpoint titrimetry (TET)

A novel yet simple, rapid and robust thermometric endpoint titration (TET) method for the determination of sodium in various foodstuffs is described. Sodium reacts exothermically with aluminium in the presence of an excess of potassium and fluoride ions to form NaK2AlF6 (“elpasolite”). This reaction forms the basis of a ro- bust, reliable analytical procedure suitable for routine process control. The reaction of calcium under similar conditions (to form KCaAlF6) suggests that potentially, calcium may interfere in the determination of sodium in some foodstuffs. Results of an investigation suggest that at molar ratios [Ca]/[Na] < 0.85, an error of <1% of the measured value of sodium is incurred.

Improved Method and Application of EMD Endpoint Continuation Processing for Blasting Vibration Signals

In order to deal with the non-stationary characteristics of blasting vibration signals and the end issue in the empirical mode decomposition(EMD), an improved endpoint continuation method is proposed. First, the linear continuation method of extreme points is used to determine the extremum of the signal endpoint fast. Secondly, the extreme points of transition section outside the signal ends are obtained by a mirror continuation method of extreme points, and then the envelope and continuation curve of the transition section of the signal are constructed. Lastly, the sinusoid of the stationary section outside the signal is constructed to achieve the continuation curve from the transition section to the stationary section. Based on the "singular extreme points" phenomenon of blasting vibration signal, the negative maxima and positive minimum are eliminated, then the maximum and minimum are guaranteed to appear at intervals. Thus,the number of iterations is reduced and the instability of EMD decomposition is improved. The calculation formula of amplitude, cycle and initial phase are given for the transition section and stationary section outside the signal. The endpoint processing effect of the simulated signal and the measured blasting vibration signal show that the improved endpoint continuation method can suppress the signal endpoint effect well.

Opportunities and challenges of clinical trials in cardiology using composite primary endpoints

In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.

Adaptive Endpoint Detection Based on Subband Speech

An adaptive endpoint detection algorithm based on band energy and adaptive smoothing algorithm is described. This algorithm utilizes the capability of adaptive smoothing algorithm that intensifies the discontinuity between local areas. The band energy features are selected because of their usefulness in detecting high energy regions (in the incoming signal) and making the distinction between speech and noise. Heuristic 'edge-focusing' is used to endpoint detection to save the time in iteration.

Endpoint Estimates for Hardy Operator's Conjugate Operator with Power Weight on n-Dimensional Space

In this paper, we establish two integral inequalities for Hardy operator＇s conjugate operator at the endpoint on n-dimensional space. The operator Hn is bounded from Lxα1 （Gn） to Lxβq （Gn） with the bound explicitly worked out and the similar result holds for Hn＊.

Prediction of Critical Endpoints Based on the PR Equation of State

In the design of chemical processes,such as catalytic cracking of bitumen and heavy oil,the knowledge of phase behavior at the critical endpoint is essential.Based on the PR equation of state,the algorithm developed by Heidemann and Khalil for calculating critical properties was used to compute critical points.An algorithm for determining the equilibrium phase of the critical point using the tangent plane criterion was developed,and was used to calculate the critical endpoints of different mixtures,including non-polar,polar and associating systems.The critical endpoint,representing the type of the phase behavior,was employed to fit the interaction parameter of mixtures in critical state at high pressure.Lines of critical endpoints for ternary mixtures were also determined with the algorithm.

In-line spectroscopy combined with multivariate analysis methods for endpoint determination in column chromatographic adsorption processes for herbal medicine

Objective: In a chromatographic cycle, the adsorption process is a critical unit operation that has a significant impact on downstream processes and, ultimately, the quality of the final products. The development of a rapid method to determine the endpoints of adsorption processes in a large-scale manufacturing is of substantial importance for herbal medicine(HM) manufacturers.Methods: In this study, the adsorption of saponins on a macroporous resin column chromatograph, a critical unit operation in Panax notoginseng(Burkill) F.H.Chen injection manufacturing, was considered as an example. The evaluation results of in-line ultraviolet and visible spectra combined with various multivariate analysis methods, including the moving block standard deviation(MBSD), difference between the moving block average and the target spectrum(DMBA-TS), soft-independent modeling of class analogy(SIMCA), and partial least-squares discriminant analysis(PLS-DA), were compared.Results: MBSD was unsuitable for adsorption processes. The relative standard errors of prediction between the predicted and experimental endpoints were 13.2%, 4.67%, and 5.71% using DMBA-TS, SIMCA, and PLS-DA, respectively.Conclusions: Among the considered analysis methods, SIMCA and PLS-DA were more effective for endpoint determination. The results of this study provide a more comprehensive overview of the effectiveness of various multivariate analysis methods to facilitate the selection of the most suitable method. This study was also conducive to address the issues of the in-line detection of adsorption endpoints to guide practical HM manufacturing.

Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials

BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.DATA SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.

Cervical spinal cord injury: tailoring clinical trial endpoints to reflect meaningful functional improvements

Cervical spinal cord injury （SCI） results in partial to full paralysis of the upper and lower extrem- ities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control （e.g., upper extremity motor score, motor level change） show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement.

ENDPOINT DETECTOR OF NOISY SPEECH SIGNAL USING A RECURRENT NEURAL NETWORK

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THE OPTIMAL CONTROL OF DELAY CONTROL SYSTEMS WITH RESTRICTED STATE RIGHT ENDPOINT

In this paper, for the delay control system: (x) over dot (t)=f[x(t), x(t-1), u(t), t] t is an element of[t(0), t(1)] x(t)=psi(t) t is an element of[t(0), t(1)] with state right endpoint restricted by condition psi(k)[x(t(1))]=0 (k=1,2,..., l) a maximum principle is given. And as a specific example, this paper gives a maximum principle under the condition that partial stares right endpoints be completely fixed. Finally, this paper gives an example to explain the application of the main result of this paper. All the results are suitable for the control systems with multidelay as well.

Application of Interpolation Inequalities to the Study of Operators with Linear Fractional Endpoint Singularities in Weighted Hölder Spaces

In this paper we consider operators with endpoint singularities generated by linear fractional Carleman shift in weighted H&#246;lder spaces. Such operators play an important role in the study of algebras generated by the operators of singular integration and multiplication by function. For the considered operators, we obtained more precise relations between norms of integral operators with local singularities in weighted Lebesgue spaces and norms in weighted H&#246;lder spaces, making use of previously obtained general results. We prove the boundedness of operators with linear fractional singularities.

A fuzzy adaptive smoothing approach to robust endpoint detection based on MDL using sub-band speech

To develop a more robust endpoint detection algorithm, this paper first proposes a fuzzy adaptive smoothing algorithm. The general idea underlying adaptive smoothing is to adapt the short-term sub-band mean of the amplitude to the local attributes of speech on the basis of discontinuity measures. The adaptive smoothing algorithm in this paper utilizes a scale-space framework through the minimal description length （MDL）. We recommend using the fuzzy muhi-attribute decision making approach to select the proper sub-bands where the word boundary can be more reliably detected. The process and simulation of the fuzzy adaptive smoothing algorithm are given. The parameters utilize the mean amplitude of the audible frequency range （300 -3 700 Hz） and the sub-band mean of the amplitude （16 band filter-bank）. We selected the audible band energy because of its usefulness in detecting high-energy regions and making the distinction between speech and noise. Otherwise, the fuzzy adaptive smoothing algorithm is processed in sub-band speech to utilize the full range of frequency information.