Pragmatic Modification Research Articles

Addressing sequential and concurrent treatment regimens in a small n sequential, multiple assignment, randomized trial (snSMART) in the MISTIC study

ABSTRACT Multisystem Inflammatory Syndrome in children (MIS-C) is a rare and novel pediatric complication linked to COVID-19 exposure, which was first identified in April 2020. A small n, Sequential, Multiple Assignment, Randomized Trial (snSMART) was applied to the Multisystem Inflammatory Syndrome Therapies in Children Comparative Effectiveness Study (MISTIC) to efficiently evaluate multiple competing treatments. In the MISTIC snSMART study, participants are randomized to one of three interventions (steroids, infliximab or anakinra), and potentially re-randomized to the remaining two treatments depending on their response to the first randomized treatment. However, given the novelty and urgency of the MIS-C disease, in addition to patient welfare concerns, treatments were not always administered sequentially, but allowed to be administered concurrently if deemed medically necessary. We propose a pragmatic modification to the original snSMART design to address the analysis of concurrent versus sequential treatments in the MISTIC study. A modified Bayesian joint stage model is developed that can distinguish a concurrent treatment effect from a sequential treatment effect. A simulation study is conducted to demonstrate the improved accuracy and efficiency of the primary aim to estimate the first stage treatments’ response rates and the secondary aim to estimate the combined first and second stage treatments’ responses in the proposed model compared to the standard snSMART Bayesian joint stage model. We observed that the modified model has improved efficiency in terms of bias and rMSE under large sample size settings.

The Induction Team Member Training Course Fitted to the Scope and Background of the Participants: A Case Study of the African Setting

Background/Introduction:The Induction Team Member (ITM) course is compulsory training for teams setting up an EMT. It encapsulates elements around safety and security, protocols and procedures, and familiarization with equipment and should happen in countries that have undergone the awareness session.1 Tailoring the ITM course to fit different countries settings and professional backgrounds is imperative, particularly in Africa, because countries have heterogeneous characteristics.Objectives:To describe the changes to the ITM Course curriculum adapted to the different professional backgrounds and technical scopes of potential team members (TM) and African countries.Method/Description:This is an After-Action Review (AAR) of in-depth feedback (n = 10) received from participants in the five trainings that have been conducted at the WHO African Regional EMT Training Center (TC) since 2021 to date. All analyses were done thematically.Results/Outcomes:The training experiences in the region have shown the need for three imperative modifications to the ITM course based on the type of EMTs and the background of the participants. These include ITM courses focusing on health workers (Doctors and Nurses); team leads, security, and logistics officials; and support staff that can work during deployment and pre-deployment tasks. An interactive ten steps to building an operational national EMTs initiative developed to fit the context has been shown as significant.Conclusion:Conceptualizing ITM course training for EMTs based on teams’ backgrounds, cultural circumstances, and political will is imperative for enhancing the capacity of regional countries’ EMTs. A pragmatic modification to the training to fit the context that captures the countries’ needs is key.

Double-Sided Transformations of Culture-Bound Constituents in William Saroyan’s Cross-Cultural Domain

The article focuses on the transformations, which occur in Russian and Armenian translations of culture-bound constituents in W. Saroyan’s fiction with special reference to the analysis of their pragmatic value and both cross-cultural and cross-language identification. The aim of the analysis is to reveal the so-called Saroyanesque identity and the translation perspectives of his specific manner of reproducing the actual reality, his personal vision of the world he lived in and created in, the world which combined the environment, circumstances, conditions, characters, cultures, ethnicity of two different communities – his native Armenian and no less native America. The so-called double-sided transformations of culture-bound constituents occur in W. Saroyan’s fiction at basically two levels: the cognitive level of ethnic and mental indicators transformations and the linguistic level of culture-bound elements translation (words, phrases, exclamations etc.). To keep Saroyanesque identity the translators should primarily transform the ideas, the concepts, the ethnic mentality of the characters, then the language media should undergo certain pragmatic modification to be correctly interpreted by the target audience.

Perception and Modification: A Pragmatic Study of Irai Hyougen by Japanese Learners

This research focused on describing how perceptions about the degree of imposition are manifested in requests in Japanese used by learners and how these perceptions are translated into choices of pragmatic modification. Through qualitative methods using the discourse completion test, it is known that perceptions of the degree of an imposition when requesting something are not manifested into the choice of request type used by learners. Instead, it is more visible from the variation in the choice of syntactic patterns used in request expression. The perception of the degree of imposition translated into a choice of external and internal pragmatic modifications. Although learners have varying perceptions of the degree of imposition for the same request, it does not appear that learners differentiate the choice of pragmatic modification based on the heaviness of the request’s imposition.

Semantic polysemy and psycholinguistics

The paper urges that polysemous phenomena are typically semantic not pragmatic. The part of a message sent by a polysemous expression is typically one of its meanings encoded in the speaker's language and not the result of pragmatic modification. The hearer receives that part of the message by a process of disambiguation, by detecting which item in the lexicon the speaker has selected. This is the best explanation of observed regularities. The paper argues that the experimental evidence from psycholinguistics, particularly that produced in discussions of “underspecification” and “overspecification,” does not undermine this view nor support the pragmatic alternative.

Guidelines on transfusion for fetuses, neonates and older children.

Guidelines on transfusion for fetuses, neonates and older children.

3Rs concerns in regulatory toxicity studies

In mid-July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which allowed ‘low risk’ psychoactive products (‘legal highs’) to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable.To investigate strategies to overcome the impasse created by the animal testing ban.Solutions to the impasse were investigated using ‘scenario’ and ‘stakeholder’ analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision-making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators.The six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non-animal test models are internationally accepted; (3) use of non-validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) ‘creative compliance’ by only presenting human clinical trial results; and (6) philosophical re-conceptualisation of the ‘benefits’ from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays.A ‘failed’ pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be included in the debate.

The challenge of a ban on animal testing for the development of a regulated legal market for new psychoactive substances (NPS) (‘legal highs’) in New Zealand: Issues and options for resolution

BackgroundIn mid-July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which allowed ‘low risk’ psychoactive products (‘legal highs’) to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable. AimTo investigate strategies to overcome the impasse created by the animal testing ban. MethodsSolutions to the impasse were investigated using ‘scenario’ and ‘stakeholder’ analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision-making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators. ResultsThe six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non-animal test models are internationally accepted; (3) use of non-validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) ‘creative compliance’ by only presenting human clinical trial results; and (6) philosophical re-conceptualisation of the ‘benefits’ from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays. ConclusionsA ‘failed’ pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be included in the debate.

Sentence Adverbials and Evidentiality

The paper deals with expressions of evidence (originating in perception, inference or reported information) and their role in sentence/utterance pragmatic modification. It concentrates on the role of the so-called sentence adverbials, showing them as scoping / focussing elements the main function of which is a/ to mark focus of an utterance b/ to support speaker´s reasoning. Formal properties of evidential expressions are dissimlar to that point that they cannot be comprised into a unified category.

Modification of capital budgeting under uncertainty

The root purpose is a slight, pragmatic modification of the traditional discounted cash flow model of real investment under uncertainty. It is motivated by the occasional inadequacy of the Net Present Value (NPV) analysis with risk. It is done in accordance with the prescribed approach to capital budgeting suggested by the well-known textbooks in corporate finance. The traditional approaches are reviewed shortly.

Accounting for the effect of concentration fluctuations on toxic load for gaseous releases of carbon dioxide

In Great Britain, advice on land-use planning decisions in the vicinity of major hazard sites and pipelines is provided to Local Planning Authorities by the Health and Safety Executive (HSE), based on quantified risk assessments of the risks to the public in the event of an accidental release. For potential exposures to toxic substances, the hazard and risk is estimated by HSE on the basis of a “toxic load”. For carbon dioxide (CO 2), this is calculated from the time-integral of the gas concentration to the power eight. As a consequence of this highly non-linear dependence of the toxic load on the concentration, turbulent concentration fluctuations that occur naturally in jets or plumes of CO 2 may have a significant effect on the calculated hazard ranges. Most dispersion models used for QRA only provide estimates of the time- or ensemble-averaged concentrations. If only mean concentrations are used to calculate the toxic load, and the effects of concentration fluctuations are ignored, there is a danger that toxic loads and hence hazard ranges will be significantly under-estimated. This paper explores a simple and pragmatic modification to the calculation procedure for CO 2 toxic load calculations. It involves the assumption that the concentration fluctuates by a factor of two with a prescribed square-wave variation over time. To assess the validity of this methodology, two simple characteristic flows are analysed: the free jet and the dense plume (or gravity current). In the former case, an empirical model is used to show that the factor-of-two approach provides conservative estimates of the hazard range. In the latter case, a survey of the literature indicates that there is at present insufficient information to come to any definite conclusions. Recommendations are provided for future work to investigate the concentration fluctuation behaviour in dense CO 2 plumes. This includes further analysis of existing dense gas dispersion data, measurements of concentration fluctuations in ongoing large-scale CO 2 release experiments, and numerical simulations.

‘Russians’ in Israel as a post-Soviet subject: implementing the civilizational repertoire

This article argues that the post-Soviet perspective on Russians in Israel allows a deeper understanding of this collective's extreme socio-cultural heterogeneity and opens up the meanings of its ‘Russianness’ often taken for granted in research literature. Empirical examples in the article trace the meanings of key cultural and sociological categories – intelligentsia and ethnicity – in the post-Soviet context, and their implementation in the Russian-Israeli field. The article stresses the potency and dominance of these categories, as well as their pragmatic usage and modification within local political and ideological contexts. The contemporary manifestation of these categories preserves the ‘civilizational’ aspect of Russian-Soviet identity, allowing their creative use by this diasporic group.

The SF-36 walk-wheel: a simple modification of the SF-36 physical domain improves its responsiveness for measuring health status change in spinal cord injury

To evaluate the validity and responsiveness of a modified SF-36 within a spinal cord-injured (SCI) population. SF-36 scores collected at baseline and on completion of a randomized controlled trial in 305 patients with SCI and neuropathic bladder. New South Wales, Australia. Subjects were administered the standard SF-36 plus three additional questions, in which 'walk' was replaced with 'wheel' for three of the physical function (PF) questions. Discriminant validity was determined by comparing participants with paraplegia and tetraplegia using the effect size (ES). Responsiveness was assessed in the subset of patients who developed a urinary tract infection (UTI) during the trial using the standardized response mean (SRM). Compared with the standard SF-36, the SF-36 walk-wheel modification (SF-36ww) increased the mean PF score from 18 to 39 (P<0.001) and the physical composite score from 33 to 37 (P<0.001). Discriminant validity was similar for both versions (PF paraplegia/tetraplegia: ES 1.09(SF-36) vs 1.08(SF-36ww), n=305). Among 138 SCI patients who developed a UTI, the SF-36ww almost doubled PF responsiveness for all neurological levels (SRM increased from 0.36 to 0.68), more so in tetraplegic (SRM, 0.11 vs 0.58; n=77) than paraplegic groups (SRM, 0.77 vs 0.86; n=61). The SF-36ww is a simple, pragmatic modification of the SF-36 PF items, which addresses some problems of content validity and floor effect for SCI subjects and greatly improves responsiveness, particularly for those with tetraplegia. Because it comprises a simple addition to the standard SF-36, external comparisons are preserved.

On a pragmatic modification of survey sampling in three stages

Presented are formulae for an unbiased estimator of a finite population total and an unbiased variance estimator for it when samples are taken by usual procedures in the first two stages with varying probabilities but the third stage units are sampled for economy and convenience in a non-standard way from the pool of all sampled second stage units rather than independently from each of the latter separately containing the former.

Linking research to extension in the Southern Highlands of Papua New Guinea: The problems of a modified farming systems approach

Farming systems research and extension (FSR/E) and on-farm trials can be effective in bringing about change in rural areas. To be so, farmer participation in planning, implementation and evaluation is absolutely essential. This paper describes the attempts of a World Bank-funded agricultural research team (AFTSEMU) in the Southern Highlands Province of Papua New Guinea to carry out relevant research and on-farm trials. The problems and general lack of success are discussed. The hidden agendas of the research workers and extension officers, the lack of genuine participation by farmers, and the supposed pragmatic modification of an ideal FSR/E model are seen as the main problems.

A Pragmatic Modification of Explicativity for the Acceptance of Hypotheses

The use of a concept called “explicativity”, for (provisionally) accepting a theory or Hypothesis H, has previously been discussed. That previous discussion took into account the prior probability of H, and hence implicitly its theoretical simplicity. We here suggest that a modification of explicativity is required to allow for what may be called the pragmatic simplicity of H, that is, the simplicity of using H in applications as distinct from the simplicity of the description of H.