Positive List Research Articles

Determination of Carbendazim and Diethofencarb in Cotton and Soil by High-Performance Liquid Chromatography

ABSTRACTA simple and reliable method was developed to determine carbendazim and diethofencarb in cotton, cotton seeds, and soil. The decomposition of carbendazim and diethofencarb in the cotton field ecosystem was also studied. The analytes were extracted and quantified by high-performance liquid chromatography. The limits of detection were 0.1 ng for carbendazim and diethofencarb. The limits of quantification of carbendazim and diethofencarb were 0.1 mg kg−1 in cotton, 0.1 mg kg−1 in cotton seeds, and 0.02 mg kg−1 in soil. The average recoveries of cotton, cotton seed, and soil were measured at three fortified concentrations and were in the range of 77.5–103.9% for carbendazim and 80.9–104.6% for diethofencarb. The relative standard deviations were less than 9.0% for both pesticides. In field experiments, the half-lives of carbendazim and diethofencarb were in the range of 2.3–9.1 days and 2.3–8.9 days in cotton at two locations in China. At harvest, cotton seeds contained carbendazim and diethofencarb well below the maximum residue limit of the Japanese “Positive List System” (3 mg kg−1) following the recommended dosage with measurement 10 and 20 days following the final application.

Determination of Diphenylamine in Agricultural Products by HPLC-FL.

A method for the determination of diphenylamine in agricultural products was developed. Diphenylamine was extracted with acetonitrile from a sample under an acidic condition, passed through a C18 cartridge column, re-extracted with n-hexane, cleaned up on a PSA cartridge column, determined by HPLC with fluorescence detector and confirmed by liquid chromatography with tandem mass spectrometry. Average recoveries (n=5) from brown rice, corn, soybeans, potato, cabbage, eggplant, spinach, orange, apple and green tea were in the range from 76.7 to 94.9%, and the relative standard deviations were from 0.6 to 5.8% at concentrations equal to the maximum residue limits (MRLs). The quantification limits were 0.01 mg/kg, which is the uniform limit in the positive list system for agricultural chemical residues in food in Japan.

Composition, labelling, and safety of food supplements based on bee products in the legislative framework of the European Union - Croatian experiences.

The European Union market is overflown by food supplements and an increasing number of consumers prefer those where bee products play an important part in their composition. This paper deals with complex European Union legislation concerning food supplements based on bee products, placing a special emphasis on their composition, labelling, and safety. Correct labelling of food supplements also represents a great challenge since, in spite of legal regulations in force, there are still open issues regarding the statements on the amount of propolis, which is not clearly defined by the legal framework. One of the key issues are the labels containing health claims from the EU positive list approved by the European Food Safety Authority. Emphasis will also be placed on informing consumers about food, as statements which imply the healing properties of food supplements and their capacity to cure diseases are forbidden. One of the key elements of product safety is HACCP based on the EU Regulations EC 178/02 and 852/2004. Health safety analyses of food supplements with bee products used as raw materials, which are standardised by legal regulations will also be discussed. In the future, attention should also be paid to establishing the European Union "nutrivigilance" system. Croatian experiences in addressing challenges faced by producers, supervisory entities, and regulatory and inspection bodies may serve as an example to countries aspiring to become part of the large European family.

China’s industrial transformation and the ‘new normal’

China’s industrial transformation faces four big roadblocks: the loss of traditional comparative advantage, weak domestic demand, low-end locking of the value chain, and structural and institutional obstacles. The shift of economic growth to structural upgrades, innovation and a service-based economy is the primary driving force required. China should implement four strategies. The first is to cultivate a new dynamic comparative advantage and inject new vitality for industrial transformation. The second is to let the market play a more decisive role and establish a long-term mechanism to expand domestic demand. The third is to promote the convergent development of global and national value chains, upgrading the value chain in horizontal and vertical axes. The fourth is to create an upgraded version of Chinese reform, manage the market with a pattern of negative listing and supervise the government with a pattern of positive listing.

Budget Impact Analysis Of Phased Radiofrequency (Rf) Catheter Ablation System In The Treatment Of Atrial Fibrillation (Af) In Turkey

To estimate the 3-year budget impact of phased RF ablation system composed of three catheters -PVAC, MASC, MAAC- for the treatment of symptomatic, drug-refractory paroxysmal or persistent AF (PAF or CAF) patients in the Turkish setting. Payer perspective is applied. Only direct costs are considered. Literature research is performed for epidemiologic data. Comparators are identified as “catheter ablation” technologies in the positive list: (1) magnetic (2) electric censored 3D-mapping catheter ablation, (3) pulmonary vein balloon cryo-ablation (Medtronic ArcticFront). Device and procedure costs are derived from positive list prices For PVAC, MASC and MAAC offer prices are taken. Complication, re-hospitalization rates and length-of-stay are similar, thus related costs are ignored. AF-related-stroke costs are calculated based on comparative single-procedure success data, AF-related-stroke risk, and AF-related-stroke costs from a local expert panel. Market shares are derived from Medtronic sales data (May 2014-May 2015) for cryo-ablation and AF market data. Two scenarios are run: (1) PVAC-only for PAF+CAF population, (2) MASC+MAAC combined with PVAC and/or ArcticFront for CAF-only. Total AF population prediction is based on 50+ population. Prevalence data is derived from several global studies. The indicated population for catheter ablation is around 5,500 patients annually, the total catheter ablation market size corresponding to one-fourth of it; mainly due to insufficient number of accredited centers and physicians. 3-year budget impact per patient is 270TL, 276TL and 334TL in first and 268TL, 274TL and 334TL in second scenario. If the limitations in quality-of-life, general health and related indirect costs are considered, the socioeconomic burden of disease would be significantly high. Indirect, long-term savings provided by significant shortening of procedure times with new technology are not included in the analysis, due to payer perspective. Considering these indirect costs and savings, the budget impact of new phased RF ablation system would be more positive.

On the roles of distinctiveness and semantic expectancies in episodic encoding of emotional words.

We examined the factors that contribute to enhanced recall for emotionally arousing words by analyzing behavioral performance, the P300 as an index of distinctiveness, and the N400 as an index of semantic expectancy violation in a modified Von Restorff paradigm. While their EEG was recorded, participants studied three list types (1) neutral words including one emotionally arousing isolate (either positive or negative), (2) arousing, negative words including one neutral isolate, or (3) arousing, positive words including one neutral isolate. Immediately after each list, free recall was tested. Negative, but not positive, words exhibited enhanced recall when presented as isolates in lists of neutral words and elicited a larger P300 for subsequently recalled than not-recalled words. This suggests that arousing, negative words stand out and that their distinctiveness contributes to their superior recall. Positive valence had an enhancing effect on recall only when the list contained mostly other positive words. Neutral isolates placed in either positive or negative lists elicited an N400, suggesting that semantic expectations developed in emotional word lists regardless of valence. However, semantic relatedness appeared to more strongly contribute to recall for positive than negative words. Our results suggest that distinctiveness and semantic relatedness contribute to episodic encoding of arousing words, but the impact of each factor depends on both a word's valence and its context.

Stress and emotional valence effects on children's versus adolescents’ true and false memory

Despite considerable interest in understanding how stress influences memory accuracy and errors, particularly in children, methodological limitations have made it difficult to examine the effects of stress independent of the effects of the emotional valence of to-be-remembered information in developmental populations. In this study, we manipulated stress levels in 7–8- and 12–14-year-olds and then exposed them to negative, neutral, and positive word lists. Shortly afterward, we tested their recognition memory for the words and false memory for non-presented but related words. Adolescents in the high-stress condition were more accurate than those in the low-stress condition, while children's accuracy did not differ across stress conditions. Also, among adolescents, accuracy and errors were higher for the negative than positive words, while in children, word valence was unrelated to accuracy. Finally, increases in children's and adolescents’ cortisol responses, especially in the high-stress condition, were related to greater accuracy but not false memories and only for positive emotional words. Findings suggest that stress at encoding, as well as the emotional content of to-be-remembered information, may influence memory in different ways across development, highlighting the need for greater complexity in existing models of true and false memory formation.

So rare we need to hunt for them: reframing the ethical debate on incidental findings.

Incidental findings are the subject of intense ethical debate in medical genomic research. Every human genome contains a number of potentially disease-causing alterations that may be detected during comprehensive genetic analyses to investigate a specific condition. Yet available evidence shows that the frequency of incidental findings in research is much lower than expected. In this Opinion, we argue that the reason for the low level of incidental findings is that the filtering techniques and methods that are applied during the routine handling of genomic data remove these alterations. As incidental findings are systematically filtered out, it is now time to evaluate whether the ethical debate is focused on the right issues. We conclude that the key question is whether to deliberately target and search for disease-causing variations outside the indication that has originally led to the genetic analysis, for instance by using positive lists and algorithms.

Generating Domain-Specific Dictionaries Using Bayesian Learning

This paper aims to operationalize subjective information processing in financial news disclosures. In order to measure news tone, previous research commonly utilizes manually-selected positive and negative word lists, such as the Harvard-IV psychological dictionary. However, such dictionaries may not be suitable for the domain of financial news because positive and negative entries could have different connotations in a financial context. To overcome the problem of words that are selected ex ante, we incorporate several Bayesian variable selection methods to select the relevant positive and negative words from financial news disclosures. These domain-specific dictionaries outperform existing dictionaries in terms of both their explanatory power and predictive performance, resulting in an improvement of up to 93.25 % in the correlation between news sentiment and stock market returns. According to our findings, the interpretation of words strongly depends on the context and managers need to be cautious when framing negative content using positive words.

PHP150 - Practical problems of comparator selection to assess cost-effectiveness of New Drugs for reimbursement decision: a qualitative study in South Korea

Under the positive drug listing system, pharmaceutical companies in Korea are required to provide cost-effectiveness (CE) evidence of newly approved drugs for listing on the National Health Insurance (NHI) drug formulary. It has been argued that selection criteria of comparator treatments suggested by the CE guideline are too limited and unrealistic to conduct a valid CE assessment. Therefore, our study was conducted to investigate types of practical problems in comparator selection in order to improve the validity of CE analysis. We conducted focus group interviews (FGI) with experts working in research-based drug companies, charged of submitting CE evidence of their products to NHI. Each participant received an interview question via an e-mail beforehand and presented their opinions at round-table discussion. Examples of the problems associated with selecting appropriate comparators identified from FGI are as follows: drugs with the same indication, but therapeutically nonequivalent, were used as comparators ; there is no guidance on whether to include off-label drugs as comparators; when off-patent products were selected as comparators, the price of the new drug was compared with the price of generic products rather than the initial price of the original products set during the patent period; it is difficult to obtain reliable market share data needed for selecting a comparator; and the best supportive care was selected as a comparator when there’s no appropriate treatment alternatives. We expect that the results of our investigation would contribute to improve the quality of CE guidelines in South Korea as well as other countries, and to improve assessment of the true value of pharmaceutical intervention.

When Criminals Control the Ministry of Education

International Action The recent focus on degree mills accompanies work on academic quality as higher education is increasingly internationalized. In Study Abroad, UNESCO published the CHEA Fact Sheet on degree mills and accreditation mills developed in 2003 as part of its alerts to this phenomenon. UNESCO and the Organization of Economic Cooperation and Development issued Guidelines for Quality Provision of Cross-Border Higher Education in 2005. The Guidelines suggest tasks for the various stakeholders in higher education—to protect quality for crossborder higher education provision to safeguard against degree mills. UNESCO has also recently launched a pilot, Portal on Higher Education Institutions, that provides international access to reliable countrywide lists of legitimate higher education providers (http://www.unesco.org/education/portal/hedinstitutions). This positive listing makes it clear that institutions that are not included may be suspect. The international group brought together by CHEA and UNESCO is working on an international effective practices statement to address the problem of degree mills. The group is also exploring additional strategies such as whether a permanent international effort is needed to address rogue providers and the feasibility of an ongoing international campaign to raise public awareness. This international effort is an ongoing need. Degree mills will continue to be a problem for students, employers, government, and higher education. They put a vital resource of our countries at risk—namely, our extensive, diverse, and highly effective higher education enterprise and the students who are served.

Towards the limiting of health risks associated with tattooing: whitelists for tattoo pigments and preservatives.

The number of pigments that could potentially be used in tattoo inks is vast. However, pigments are generally not manufactured for the purpose of being injected into subepidermal layers of the skin. Assuming 100% bioavailability after injection means that pigments can be imminently hazardous to human health. Given the ever-increasing number of pigments being circulated on the market or through the internet, a 'negative list' ('black' list) containing pigments with known adverse effects will never be finalised. If incriminated, substances could easily be replaced by structurally similar pigments that might be even more deleterious to human health. Therefore, we and others suggest the establishment of a whitelist ('positive list') that would only contain pigments that had undergone a risk assessment specifically for their application into the dermis. Some of the problems associated with such a 'positive list' are discussed. Another important issue with regard to tattoo safety is related to the preservatives used in ink preparations. Notwithstanding the demand for sterile tattoo inks, a whitelist for these compounds would be beneficial. At present, many technical preservatives are being used, despite their known detrimental effects to human health. Criteria for the inclusion of preservatives in a 'positive list' are also discussed.

Cage-enrichment: rabbit does prefer straw or a compressed wooden block

The effect of different food related materials on the behaviour of commercial meat rabbit does was investigated to provide them enrichment. Five different treatments were tested. Control (pens without additional enrichment, C) was compared with pens containing a pinewood stick (Pine), straw in a plastic bin (Straw), a compressed wooden block (Ply) or a combination of straw and a pinewood stick (Straw+Pine). The experiment was conducted on a commercial rabbit farm using 80 cages with multiparous lactating hybrid (Hycole) rabbit does. Behavioural observations were conducted in the first 4 wk of 2 successive lactations of 6 wk each, twice a week from 15:00 to 18:30 h. Once every week the consumption of gnawing materials and soiling of the cages was scored. More does were significantly occupied with Straw and Ply than with Pine (24±20, 11±9 and 4±3% of does, respectively) for a longer duration (4±4, 2±2, 0.1±0.2% of observed time, respectively). In does of Straw+Pine group, the pinewood was barely touched and straw was preferred. It can be concluded that straw (loose material) and wooden block are used by the animals as enrichment material to gnaw or chew on. The materials remain attractive for the 2 lactations which were measured. The pinewood stick as provided in this study was rarely used and it may be questioned whether it is sufficient as enrichment material or if it should be provided in another way than hanging on the roof of the cage. This study provides a first step towards a positive list of enrichment materials that can be used in commercial rabbit farming in The Netherlands.

Generic Imatinib in a Patients with Chronic Myeloid Leukemia in Chronic Phase- a Single Centre Experience

Imatinib (Gleevec) has shown long-term efficancy and safety in published randomized clinical trials. Anzovip (Imatinib) is a new generic drug produced by Zdravlje Actavis,which was approved by the Medicines and Medical Devices Agency of Serbia in January 2012. In July 2012, National Health Insurance Fund of Serbia introduced this drug in the positive list. All the patients using Glivec were switched to Anzovip and all newly diagnosed patients started with Anzovip therapy. In this study, hematologic and cytogenetic responses were evaluated in CML patients who received generic Imatinib as the first line therapy and in patients who switched from branded Imatinib to an Imatinib copy drug.Materials and methods. During August and September 2012, all the patients were switched from Glivec to Anzovip and all new CML patients were treated with Imatinib copy. 55 patients treated with branded Imatinib were switched to generic Imatinib. Out of 17 newly diagnosed patients with CML-CP, who started with generic Imatinib, 7 patients could be followed up for 18 months. All patients underwent hematologic, cytogenetic monitoring based of the recommendations of the ELN.Results. These are the results of using Anzovip after 18 months. Of the 55 patients who were switched from branded Imatinib to Imatinib copy, 11 patients (20 %) have lost complete cytogenetic response they already had, but without signs of biological illness transformation. They were switched to 2nd line therapy nilotinib.Of the 7 newly diagnosed patients who started with genereic Imatinib, all 7 patients (100%) have achieved complete hematologic response (CHR) in the period of 6 months. 3 (42,8%) patients have achieved CCgR and 2 patients (28,6%) have achieved MMR in the period of 12 months. 57% of patients have switched to second generation of TKI because of failure or intolerance according to ELN and national recommendation. The drug has been well tolerated, wild mild adverse event, more frequently, fluid retention and gastrointestinal symptoms. Only one patient have had skin changes grade ¾ and he has been switched to second generation of TKI.Conclusions. It is unknown whether patients, who responded to branded Imatinib and than switched to its copy versions, will tolerate the copy drug and maintain the previous response. Because of that, it is important to careful follow up of a selected patients several months after the switch to generic imatinib. Despite of the small number of patients who started with Imatinib copy, our results in term of hematologic and cytogenetic response were close to the international series. DisclosuresUrosevic:Novartis: Consultancy, Honoraria. Savic:Roche: Honoraria; NovoNordisc: Honoraria. Rajic:NovoNordisc: Honoraria.

Health technology assessment in the Balkans: opportunities for a balanced drug assessment system

Countries in the Balkan region use pharmaco-economic data for decisions about the inclusion of new pharmaceuticals into their positive drug lists, but no predefined frameworks are used and resources for health technology assessment (HTA) are limited. The goal of this analysis is to investigate into possible development directions for the HTA system in the region, and provide some practical recommendations for a sustainable model. For this purpose, the main factors currently influencing HTA in Balkan countries are briefly presented, and possible development strategies are compared. A resource-saving balanced assessment approach is proposed. It is aligned with available resources and capabilities, and helps access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget.

Negotiating Exclusions in Developing Country FTAs

There exists a choice of negotiating the exclusions in tariff liberalization: negative or positive listing. The extent of coverage caters to all sectors/products minus an identified ‘sensitive list’ under the negative list approach is considered more liberalizing than positive listing with coverage across a specific number of sectors/products selected for preferential treatment. However, as there is no predetermined method of expansion of liberalization content during phase-in periods, it is necessary to compare both methods of negotiating exclusions, as each is perceived as a new policy for stakeholders having corresponding legal, administrative and economic implications.

The brain, cognitive enhancement devices, and European regulation.

Exciting advances in neuroscience have given rise to devices—now being sold worldwide—which hold the promise of enhancing human cognition. This concerns Maslen et al.—authors of the article, The Regulation of Cognitive Enhancement Devices: Extending the Medical Model—because there are unaddressed possible harms from such equipment. Cognitive enhancement devices (CEDs) are currently entering the European market without special regulations. Their unique ability to influence the brain in potentially deleterious ways is not being accounted for by the law, exposing consumers to risk. In arguing for such regulation, Maslen et al. present risk analyses of certain devices that interact with the brain. They then propose CED-specific additions to existing European medical device regulation. First, they recommend a positive list of CEDs to be regulated. Second, they offer a three-tiered framework for categorizing CEDs, determining market approval, and what level of government scrutiny they receive based on risks and benefits. The authors’ assessment, while demonstrating legitimate concerns, presents a flawed analysis of CEDs and is ultimately unnecessary. We disagree with their definition of CEDs and classifications for certain devices. Moreover, we believe that the regulatory gap Maslen et al. seek to address is not as profound as they portray. Steps are underway to fill this gap in the immediate future, obviating the need for their proposal. Finally, we argue that the authors incorrectly balance risk and benefit when determining CED market approval.

KeyPathwayMiner 4.0: condition-specific pathway analysis by combining multiple omics studies and networks with Cytoscape.

BackgroundOver the last decade network enrichment analysis has become popular in computational systems biology to elucidate aberrant network modules. Traditionally, these approaches focus on combining gene expression data with protein-protein interaction (PPI) networks. Nowadays, the so-called omics technologies allow for inclusion of many more data sets, e.g. protein phosphorylation or epigenetic modifications. This creates a need for analysis methods that can combine these various sources of data to obtain a systems-level view on aberrant biological networks.ResultsWe present a new release of KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics data sets, e.g. gene expression, but is able to directly combine several different omics data types. Version 4.0 can further integrate existing knowledge by adding a search bias towards sub-networks that contain (avoid) genes provided in a positive (negative) list. Finally the new release now also provides a set of novel visualization features and has been implemented as an app for the standard bioinformatics network analysis tool: Cytoscape.ConclusionWith KeyPathwayMiner 4.0, we publish a Cytoscape app for multi-omics based sub-network extraction. It is available in Cytoscape’s app store http://apps.cytoscape.org/apps/keypathwayminer or via http://keypathwayminer.mpi-inf.mpg.de.

Food contact substances and chemicals of concern: a comparison of inventories

Food contact materials (FCMs) are intended to be in contact with food during production, handling or storage. They are one possible source of food contamination, because chemicals may migrate from the material into the food. More than 6000 FCM substances appear on regulatory or non-regulatory lists. Some of these substances have been linked to chronic diseases, whilst many others lack (sufficient) toxicological evaluation. The aim of this study was the identification of known FCM substances that are also considered to be chemicals of concern (COCs). The investigation was based on the following three FCM lists: (1) the 2013 Pew Charitable Trusts database of direct and indirect food additives legally used in the United States (or Pew for short), (2) the current European Union-wide positive list for plastic FCMs (or Union for short), and (3) the 2011 non-plastics FCM substances database published by EFSA (or ESCO for short). These three lists of food contact substances (Pew, Union, ESCO lists) were compared with the Substitute It Now! (SIN) list 2.1, which includes chemicals fulfilling the criteria listed in article 57 of Regulation (EC) No. 1907/2006 (REACH), and the TEDX database on endocrine-disrupting chemicals. A total of 175 chemicals used in FCMs were identified as COCs. Fifty-four substances present on the SIN list 2.1 were also found on the Union and/or ESCO lists. Twenty-one of those 54 substances are candidates for Substances of Very High Concern (SVHC), and six of these 21 are listed on Annex XIV and intended for phase-out under REACH. In conclusion, COCs used in FCMs were identified and information about their applications, regulatory status and potential hazards was included.

Comparative evaluation of alcoholic handrub: science or marketing?

We read with interest but also with some astonishment the paper of Kampf et al.[1] comparing the efficacy of three alcoholic-based hand-rubs (ABHR) according to EN 1500 and EN 14476. This study highlighted the possible variability of the results in different laboratories suggesting that the norm methods must be improved for a better standardization (EN 1500 and PrEN 1500). Although the methodology of the experiments seems robust, we do not understand why only three products used in French hospitals were tested and why the positive list of the French Society for Hospital Hygiene (SFHH) was targeted by Kampf et al. in the tittle and in the discussion section of the paper. As two of the authors are employed by Bode Chemie GmbH, a competing company of the French companies that manufactured the ABHR tested, there are real competing interests as mentioned at the end of the paper. We want to underscore also that this kind of paper is able to discredit some widely used products, represents a threat to hand hygiene promotion and the confidence in disinfectants if it is misunderstood and misused. As for some other controversial papers about the efficacy of ABHR [2-4] the French Society for hospital Hygiene and the Disinfectant Commission of the German Association for Applied Hygiene (VAH)a want to remind that independent testing of disinfectants is an important criterion to select active from non- active substances and therefore an essential instrument for quality assurance for disinfectants. To guarantee the activity and reliability under practical conditions the education of healthcare workers in the application of efficient hand disinfectants is a key point. The role of hospital hygiene societies is to promote efficient hand rub use for better hand hygiene in healthcare settings. In 2010, the SFHH choose to end the positive list and begin the writing of guidelines to help healthcare settings to choose disinfectants. The SFHH (now named SF2H) never claimed to be able to control completely the validity of the tests performed and always reminded the readers that the manufacturers and the laboratories that tested the products were responsible for the results of the efficacy tests. On the contrary of Germany, the French Society for Hospital Hygiene do not evaluated on its own responsibility the efficacy of the products. The analyses of the test reports provided by the manufacturer were free and independent. We think that the French positive list has had a positive impact to promote handrub use and despite its limitations permitted to select adequate products for use in healthcare settings [5]. These efforts are necessary also for the future. In Germany the list of tested and by an independent commission of experts approved disinfectants is continued and seemed to be a valuable instrument. In the German philosophy consumer should not be only dependent on the information of companies and industries. To come back to scientific purpose, this study suggests that the norm methods to test ABHR efficacy must be improved for better standardization, but we don’t agree with all priorities proposed by Kampf et al. to improve the validity of products and efficacy claims. We agree with the fulfilling of European pertinent norms and with the necessity to revise regularly the European norms to take into account the observed bias as for example the type of columns in the virucidal test. A better public control of norms and biocide authorizations is needed notably because of the increasing number of news ABHR products.