Unequal Distribution of Innovation Efforts for Neglected Tropical Diseases: The Role of Funding Evaluation Criteria

Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. Methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. Societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, current application of evaluation criteria leads to a primary focus on short-term impact. Through current practice, the relatively most neglected diseases will remain so, and a long-term strategy is needed to resolve this.

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

In 2017,immune response evaluation criteria in solid tumors(iRECIST)were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy,considering the different time of following and response,between this new therapy compared to the standard one.However,even if the iRECIST are worldwide accepted,to date,different aspects should be better underlined and well reported,especially in clinical practice.Clinical experience has demonstrated that in a non-negligible percentage of patients,it is challenging to determine the correct category of response(stable disease,progression disease,partial or complete response),and consequently,to define which is the best management for those patients.Approaching radiological response in patients who underwent immunotherapy,a new uncommon kind of target lesions behavior was found.This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug.Therefore,new groups of response have been described in clinical practice,defined as“atypical responses,”and categorized into three new groups:pseudoprogression,hyperprogression,and dissociated response.This review summarizes and reports these patterns,helping clinicians and radiologists get used to atypical responses,in order to identify patients that respond best to treatment.

Development of Brief Image Quality Evaluation Criteria for Digital OrthoPantomography （OPG） Images in Dental Radiography

An OPG （orthopantmography） is an extra-oral radiographic imaging method which provides a panoramic or wide view of both jaws and teeth on a single image. Digital OPG images provide high contrast with more details of the dentitions. The research main objective was to produce sophisticated and effective criteria that can be used by any radiographer with sound knowledge to identify common errors of digital OPG images and to increase the concern of high frequency of errors to minimize them to give an optimum image quality. The study was designed as retrospective cross sectional study. Hundred digital OPG images are evaluated by three qualified radiographers who had dental radiography experience and four student radiographers. Paired t-test was used to see the difference between the responses of radiographers and student radiographers. Kruskal-Wallis Test was used to see difference between each evaluator. Possible errors of OPG were divided into four main categories （identification, artifact, anatomical coverage and patient positioning）. Each main category consists of sub-categories. Values of subcategories were given according to their importance to get the total of 100% for each main category. The results showed that there is no significant difference between radiographers and student radiographers’ responses and also between each evaluator. Hence it shows that the criteria were an easy understandable and user-friendly tool. And results showed the frequent error category was loss of anatomical coverage and frequent error was absence of positioning the tongue against the palate.

Comparison of neutron energy spectrum unfolding methods and evaluation of rationality criteria

The neutron energy spectrum was measured using a Bonner sphere spectrometer at six locations inside the containment vessel of a nuclear reactor at the Qinshan nuclear power plant. The structures of the neutron spectra obtained by the maximum entropy, iteration, and genetic algorithm methods were consistent with one another and could be interpreted as the spectral superposition of different energy regions. The characteristic parameters of the neutron spectrum, including the fluence rate,average energy, and neutron ambient dose equivalent rate H^(*)(10), were in good agreement among the three methods. In addition, an LB6411 neutron ambient dose equivalent meter was employed to obtain the H^(*)(10) directly for comparison.These findings indicate that neutron spectrum unfolding methods can be used to overcome the problems associated with the response functions of dosimeters to provide more accurate H^(*)(10) values. In this study, the following three evaluation criteria were systematically addressed to ensure the accuracy of the unfolded spectra: count rates of the inverse solutions,neutron spectrum structures, and comparison of key parameters.

Evaluation criteria, major types, characteristics and resource prospects of tight oil in China

Tight oil refers to a petroleum play that occurs in a free or adsorbed state in source rocks or tight reservoir rocks(e.g.,sandstone and carbonate rock)interbedded with or close to source rocks.Tight oil has generally not experienced large-scale,long-distance migration.According to such a definition and its characteristics,10 key indices are proposed for tight oil resource evaluation in China.Tight oil reservoirs are divided into three groups in terms of porosity and permeability.Tight oil can be classified into three types according to the contact relationship between the tight oil reservoirs and source rocks,i.e.,tight lacustrine carbonate oil,tight deep-lake gravity flow sandstones oil,and tight deep-lake deltaic sandstones oil.In China,tight oil resources are widely distributed and significant exploration discoveries have been achieved in the sixth member and seventh member of the Triassic Yanchang Formation in the Ordos Basin,the Permian Lucaogou Formation in the Junggar Basin,the Middle-Lower Jurassic strata of the Sichuan Basin,and the Cretaceous Qingshankou and Quantou Formations in the Songliao Basin.The total geological resources of tight oil in China assessed by using the“analog”method are estimated to be(10.67-11.15)×10^(9) tones.Taking into account of the future prospects of petroleum development,tight oil may become a realistic alternative to the conventional oil resources in China.

Exploration of Key Points in Evaluation Criteria of Chinese Medicine in the Treatment of Cancer

Although tumor node metastasis （TNM） staging in WM has been accepted and used with no reserve in the criteria of CM diagnosis and treatment of cancer, some differences still exist between CM and WM in the evaluation criterion. The reason for this focuses on evaluation criterion of effects on solid tumor made by the World Health Organization （WHO）, which does not reflect some aspects such as survival time of tumor patients or improvement in quality of life （QOL）. Therefore, forerunners in the CM field have been making efforts to try to find an evaluation criteria that would integrate CM and WM, and thus could be approved by CM and WM specialists.

Research and perspectives on criteria for evaluation of nursing research achievements

This paper introduces concepts related to scientific research achievements, analyzes current evaluation methods with regard to nursing research achievements and their application at home and abroad, and summarizes findings from the investigation of obstacles to the application of nursing research results in China, aiming to provide reference points for the evaluation and application of nursing research results in China.

Relative accuracy of spatial predictive models for lynx Lynx canadensis derived using logistic regression-AIC,multiple criteria evaluation and Bayesian approaches

We compared probability surfaces derived using one set of environmental variables in three Geographic Information Systems （GIS） -based approaches： logistic regression and Akaike＇s Information Criterion （AIC）, Multiple Criteria Evaluation （MCE）, and Bayesian Analysis （specifically Dempster-Shafer theory）. We used lynx Lynx canadensis as our focal species, and developed our environment relationship model using track data collected in Banff National Park, Alberta, Canada, during winters from 1997 to 2000. The accuracy of the three spatial models were compared using a contingency table method. We determined the percentage of cases in which both presence and absence points were correctly classified （overall accuracy）, the failure to predict a species where it occurred （omission error） and the prediction of presence where there was absence （commission error）. Our overall accuracy showed the logistic regression approach was the most accurate （74.51%）. The multiple criteria evaluation was intermediate （39.22%）, while the Dempster-Shafer （D-S） theory model was the poorest （29.90%）. However, omission and commission error tell us a different story： logistic regression had the lowest commission error, while D-S theory produced the lowest omission error. Our results provide evidence that habitat modellers should evaluate all three error measures when ascribing confidence in their model. We suggest that for our study area at least, the logistic regression model is optimal. However, where sample size is small or the species is very rare, it may also be useful to explore and/or use a more ecologically cautious modelling approach （e.g. Dempster-Shafer） that would over-predict, protect more sites, and thereby minimize the risk of missing critical habitat in conservation plans .

Assessing Financial Management Practices and Accounting Mechanisms in Agricultural Cooperatives:A Case Study From Nepal

The study focuses on assessing the financial management practices and accounting mechanisms in agricultural cooperatives in Tulsipur Sub-Metropolitan,Dang District,Nepal with a focus on understanding their implications for financial performance and organizational effectiveness.The sample size of total cooperatives(n=46)was divided into Savings and Credit Cooperatives(n=18)and Multipurpose Cooperatives(n=28),respectively,with a total number of respondents(n=138)categorized into managing directors,employees,and general members.Using a mixed-methods approach that combines quantitative analysis of financial data with qualitative insights gathered through interviews and surveys,the study emphasizes the importance of modern financial practices,improved reporting mechanisms,and relevant staff training for long-term sustainability.Recommendations include the integration of criteria and evaluation tools to assess cooperative performance,with Hamro Pahunch Multipurpose Cooperative identified as a high performer.Emphasizing the need for robust financial management strategies to navigate the complexity of the agricultural sector,manage risks,and achieve sustainable development,the study notes frequent preparation of financial management reports on a monthly and annual basis,and predominantly annual accounting management.Most cooperatives are using computerized models to present financial positions,but face challenges such as lack of marketing infrastructure,cooperative skills,and technical support.Ultimately,the study advocates for educating policy makers,cooperative leaders,practitioners and stakeholders on the role of effective financial management and accounting in enhancing the resilience,expansion and socio-economic impact of agricultural cooperatives,thereby fostering their long-term prosperity and viability as drivers of rural development and empowerment.

New approaches for precise response evaluation in hepatocellular carcinoma

With the increasing clinical use of cytostatic and novel biologic targeted agents,conventional morphologic tumor burden assessments,including World Health Organization criteria and Response Evaluation Criteria in Solid Tumors,are confronting limitations because of their difficulties in distinguishing viable tumor from necrotic or fibrotic tissue.Therefore,the investigation for reliable quantitative biomarkers of therapeutic response such as metabolic imaging or functional imaging has been desired.In this review,we will discuss the conventional and new approaches to assess tumor burden.Since targeted therapy or locoregional therapies can induce biological changes much earlier than morphological changes,these functional tumor burden analyses are very promising.However,some of them have not gone thorough all steps for standardization and validation.Nevertheless,these new techniques and criteria will play an important role in the cancer management,and provide each patient more tailored therapy.

Literature review of material evaluation

A literature-based review concerning why and how to evaluate language-teaching materials is presented with the purpose to facilitate English Language Teachers＇ awareness of material evaluation and assist their conduction.

Method of effective evaluation for examination of chloride ion in concrete

The chloride ion contained in reinforced concrete seriously corrodes the steel surface and damages concrete, resulting in inferior reinforced concrete that strength seriously compromises the entire structure’s safety. Consequently, the examination of chloride ions contained in reinforced concrete becomes an important part of a complete quality control procedure. To effectively check the concentration of chloride ions in concrete, the evaluation process should be accurate and precise. Laboratory data ob- tained using existing evaluation methods for the examination of chloride ion are not sufficiently objective to yield reliable results with accuracy and consistency for each sample. An evaluation algorithm with capability to define indices of precision degree (Ep) and accuracy degree (Ea) is presented in this paper. The authors established a statistically reliable index of unbiased estimators and equations to critically examine the laboratory methods’ precision, accuracy degrees and application value for measuring chlorine ion concentration in reinforced concrete.

Reliable evaluation method of quality control for compressive strength of concrete

Concrete in reinforced concrete structure (RC) is generally under significant compressive stress load. To guarantee required quality and ductility, various tests have to be conducted to measure the concrete’s compressive strength based on ACI (American Concrete Institute) code. Investigations of recent devastating collapses of structures around the world showed that some of the collapses directly resulted from the poor quality of the concrete. The lesson learned from these tragedies is that guaranteeing high quality of concrete is one of the most important factors ensuring the safety of the reinforced concrete structure. In order to ensure high quality of concrete, a new method for analyzing and evaluating the concrete production process is called for. In this paper, the indices of fit and stable degree are proposed as basis to evaluate the fitness and stability of concrete’s compressive strength. These two indices are combined to define and evaluate the quality index of the compressive strength of concrete. Prin-ciples of statistics are used to derive the best estimators of these indices. Based on the outcome of the study, a concrete compres-sive strength quality control chart is proposed as a tool to help the evaluation process. Finally, a new evaluation procedure to assess the quality control capability of the individual concrete manufacturer is also proposed.

Extension of Paraconsistent Many-Valued Similarity Method to Group Decision

The Paraconsistent Many-Valued Similarity (PMVS) method for multi-attribute decision making will be incomplete as a decision model if it is not extended to the realm of group decision-making. Therefore, in this article, our primary objective is to show how the paraconsistent many-valued similarity method can be used to solve group decision-making problems involving choice making or ranking of a finite set of decision alternatives. Moreover, since weights are very important parameters in multi-attribute decision-making, we have introduced the Borda rule to calculate the weights of experts and that of every criterion under consideration. To demonstrate how the proposed method works, a numerical example on energy sources of an economy from the points of view of a group of experts is investigated. Further, we compare the results of this new approach with that of fuzzy TOPSIS group decision-making method to illustrate the robustness and effectiveness of the former.

A Ship Officer Performance Evaluation Model Using Fuzzy-AHP

A ship＇s crew plays an important role in the maritime transportation sector and their performance is paramont in the shipping industry. On this account, an impartial evaluation of the crew＇s performance is an important issue. In this paper, the ship officer＇s performance evaluation problem is studied. The performance evaluation criteria that shipping companies take into account are determined and a performance evaluation process is modelled by using the FAHP （Fuzzy Analytic Hierarchy Process） based on Chang＇s Algorithm. Linguistic variables and fuzzy numbers are used in the assessment process. The results of the proposed model demonstrate that the FAHP method is effective and helps managers make better and more reliable decisions under fuzzy circumstances.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

Comparison of RECIST version 1.0 and 1.1 in assessment of tumor response by computed tomography in advanced gastric cancer

Objective： Response Evaluation Criteria in Solid Tumors （RECIST） guideline version 1.0 （RECIST 1.0） was proposed as a new guideline for evaluating tumor response and has been widely accepted as a standardized measure. With a number of issues being raised on RECIST 1.0, however, a revised RECIST guideline version 1.1 （RECIST 1.1） was proposed by the RECIST Working Group in 2009. This study was conducted to compare CT tumor response based on RECIST 1.1 vs. RECIST 1.0 in patients with advanced gastric cancer （AGC）. Methods： We reviewed 61 AGC patients with measurable diseases by RECIST 1.0 who were enrolled in other clinical trials between 2008 and 2010. These patients were retrospectively re-analyzed to determine the concordance between the two response criteria using the κ statistic. Results： The number and sum of tumor diameters of the target lesions by RECIST 1.1 were significantly lower than those by RECIST 1.0 （P〈0.0001）. However, there was excellent agreement in tumor response between RECIST 1.1 and RECIST 1.0 0（κ=0.844）. The overall response rates （ORRs） according to RECIST 1.0 and RECIST 1.1 were 32.7% （20/61） and 34.5% （20/58）, respectively. One patient with partial response （PR） based on RECIST 1.0 was reclassified as stable disease （SD） by RECIST 1.1. Of two patients with SD by RECIST 1.0, one was downgraded to progressive disease and the other was upgraded to PR by RECIST 1.1. Conclusions： RECIST 1.1 provided almost perfect agreement with RECIST 1.0 in the CT assessment of tumor response of AGC.

How to assess the efficacy or failure of targeted therapy:deciding when to stop sorafenib in hepatocellular carcinoma

Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma(HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate(from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria(European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques(computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor(hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alphafetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data(in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival(Child-Pugh class, Barcelona Clinic Liver Cancer, alphafetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.

Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer

Background： The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors （RECIST） version I. 1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 （measuring two target lesions per organ） and modified RECIST I. 1 （measuring the single largest lesion in each organ） in patients with small cell lung cancer （SCLC）. Methods： We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography. Results： There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST I.I. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria （k= 1.0）. Conclusions： The modified RECIST 1.I showed perfect agreement with the original RECIST 1.I in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.

Objective response rate assessment in oncology: Current situation and future expectations

The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.