dataesr/scientific-paragraphs-categorization huggingface dataset:
Calculating sample size for a third MiQuit RCT Trial Sequential Analysis has demonstrated that further RCT data are required before a firm conclusion about MiQuit efficacy can be determined. As the initial two trials were sufficiently similar to be combined in Trial Sequential Analysis, we will now demonstrate how Trial Sequential Analysis can be used to estimate the sample size for (a) further trial(s)data from which, when combined with the previous two trials in the Trial Sequential Analysis software, would be expected to provide a more decisive answer regarding MiQuit efficacy. We will also demonstrate how exemplar theoretical findings from future trials which are both in favour and against MiQuit having a positive effect would impact the Trial Sequential Analysis result.
Sensitivity analysis The modelled scenario, in which there is no heterogeneity between trials in a meta-analysis is rare; in most situations where the described approach is used, some heterogeneity between studies is to be expected. Trial Sequential Analysis provides 95% confidence intervals for heterogeneity (D 2 ) within meta-analyses. One way to fully allow for heterogeneity is to perform a sensitivity analysis using the upper 95% confidence interval for the between-trial heterogeneity variance estimate. This would increase the required information size. In our example, the program could not calculate the 95% confidence interval surrounding the D 2 of 0% as there were less than three included studies. In this case it is possible to input an estimate for heterogeneity into the Trial Sequential Analysis software.
Discussion The above example demonstrates how Trial Sequential Analysis can be used to determine the required sample size for one or more additional RCTs to make a metaanalysis more conclusive. This sample size would be considered underpowered in comparison to a traditional RCT sample size calculation. By using Trial Sequential Analysis in such a way, future trials could be planned using significantly fewer resources and with less cost than trials planned using traditional sample size calculations. In the worked example, data from the pilot trial were used in the Trial Sequential Analysis to estimate the required information size. Ignoring that the same data is being used twice (for the estimation and for the meta-analysis) could mean that the estimate generated is not sufficiently conservative.
Box 1 Categories of PPE in the EU. EU regulation 2016/425  (EU, 2016)  classifies PPE into three risk categories (found in Appendix 1 of the regulation): -Category I: work equipment covering minimal risks; -Category III: safety equipment for risks that may have irreversible or deadly consequences; -Category II: specific protective equipment for risks other than those provided for in categories I and III. All apparel for personal protection from chemical hazards (including pesticides) is considered as having to protect from serious risk, and fall under category III. farmers' economic ability to purchase PPE and follow occupational safety advice). Most of the literature available on international databases concerns OECD countries, and the following analysis concentrates on them.
Selecting articles for analysis Three major databases were searched for articles using search terms in English and with no date restrictions. Literature reviews were also included. Unpublished research findings were not taken into consideration. Articles were included if they provided information on the assessment of the effectiveness of coveralls used for PPP protection in OECD countries. All forms of assessment were retained: discussion of the real effectiveness of PPE against the underlying assumptions of marketing authorisation procedures, laboratory tests of equipment, and field tests with controlled and uncontrolled PPE wearing practices. Articles on the efficiency of occupational safety instructions based on using such coveralls were also included. Initially 86 articles were identified on the Scopus database (43 were selected), 21 on the Pascal database (9 selected), and 81 on the PubMed database (31 selected).
This factor is intended to take account of inter-and intra-species variations. If the exposure level estimated with such models is greater than the reference values, the models predictively consider that the estimated exposure value could be reduced by wearing PPE. The protective factor attributed to wearing PPE varies according to the type of PPE and the part of the body concerned. It may also vary depending on the availability of observational data, especially in national databases  (Hinz and Hornicke, 2001). When data on the protection provided by PPE is lacking, EFSA (2014a) recommends using default values, in this case considering that coveralls let through a maximum of 5-10 per cent of the product to which users are exposed (Table  1 ). This amounts to assume that this equipment can reduce PPP exposure by 90 to 95 per cent.
Also, the NMO did not have access to the information provided by the patients to the survey, this information was only accessible by PAREXEL and linked to the unique country-specific identification number. Recruitment was monitored to ensure patients were equally represented in each of the following groups: IVIg in hospital, IVIg at home, SCIg in hospital and SCIg at home. Study participants could withdraw from the study at any time by not completing the questionnaire or by requesting withdrawal from their NMO contact. If patients decided to withdraw, no new data were collected from them and they were not contacted again. However, the anonymous data collected before their withdrawal would still be used in analyses, reports, conference presentations, and academic journal publications.
Statistical Analyses The data file was originally received in Excel. This was converted to SPSS v22. On SurveyMonkey, most of the 133 questionnaire items suitable for the psychometric analysis (the 129 items + the four dummy items) used a Verbal Rating Scale ranging between 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often and 5 = Always. A small subset of items also included an additional "Not Applicable" response category (coded as 6). For the purposes of this analyses, the data were recoded from 0 to 5 (5 = Not Applicable) to support an eventual scoring algorithm of 0-100 (in line with most questionnaires). Only patients that gave consent to use their survey data were included in the final analysis. Exploratory factor analysis (EFA), a method of classical test construction, was carried out which included the "not relevant" responses in the procedure.
Following this only one dummy question remained which was also removed ("felt negative about my treatment") because after checking the pattern of scoring with its twin question, the pattern of scoring was in the appropriate direction. The overall Ig burden item was also excluded. Given that most of the positively worded items had been removed, it was decided to also remove the remaining seven positively phrased items to avoid the complexities of possible recoding and interpreting negative correlations for potential users of the new measure in the future. Therefore, a total of 80 items were excluded leaving 53 items that were used in the first round of factor analysis. Following discussions within the clinical and statistical team, for the purposes of the factor analysis, those patients that answered "not applicable" to any item were recoded to 0 meaning "never", rather than designated missing from the dataset.
Face validity was also demonstrated in a smaller survey with UK patients reported elsewhere. Whilst this survey has substantially reduced the questionnaire, identified the domain structure, scoring algorithms and aspects of reliability, based upon the FDA guidance for the development of PROMS, there are still a number of other psychometric analyses to undertake. 19 Therefore, a second online survey with patients undergoing Ig therapy in the US is currently being undertaken using this shorter measure. This study will be used to test the current model of the IgBoT-35 and reduce it further if appropriate. The data will also be used to evaluate the other psychometric properties of the questionnaire which are currently undetermined, such as aspects of construct and criterion validity using "a priori" hypotheses developed by the team.
Limitations There were some limitations to the study. Due to the need to translate the questionnaire into nine different languages, the format of some of the changed based upon the outcome of the cognitive interviewing. The most important change was that on the initial paper version of the instrument, it was only planned to have the header question "because of my current Ig treatment, I have …. " at the top of each page. However, due to the nature of SurveyMonkey, this was changed so that this header was used at the start of each item. This made some of the items long and more challenging to read, for example, "because of my current Ig treatment, I have found that my Ig treatment takes up too much time. " Given the extent of item reduction that was needed with this first survey, item reduction was undertaken cautiously and there is potentially scope for some more item redundancy.
There may also be problems with the "consequence of treatment" domain as some of these items cross-loaded but this will be explored further in the new data set before confirming the final domain structure. It may be that this domain will be shortened or removed depending on the results from the next set of analyses. The whole questionnaire (including the demographic and IgBoT questions) that was entered onto SurveyMonkey was long and included 151 items. There was evidence of questionnaire fatigue because missing data was more evident towards the end of the questionnaire but unfortunately, we did not record completion times. Ideally, more time and opportunity to validate the different language versions of the questionnaire prior to being migrated from the paper to electronic version would have been beneficial (beyond the five patients per country used by MAPI who undertook cognitive debrief interviews on the paper version before it was uploaded).
Acknowledgments We are grateful to i) all the patients who gave their time to take part in this research, ii)  Professor John Brazier  for his contribution to the development of the study protocol, iii) Mia Malmenas from PAREXEL and  Teresa Kauf  formerly from  Shire , a  Takeda company  for their support and contribution to the development and delivery of this study, iv)  Dr Betschel ,  Dr Whitney Goulstone ,  Dr Børre Fevang ,  Dr Martin Van Hagen ,  Dr Martin Buckland , and  Prof Claudio Pignata  for their assistance with our ethics committee applications. The abstract of this paper was presented at the Advances in Patient Reported Outcomes:  Integration and Innovation Conference, Leeds, UK , 13th June 2019 as an oral presentation with interim findings. The abstract has been published in the Journal of Patient-Reported Outcomes 2020, 4(Suppl 1): 28.
Independent variables Demographic data were collected, including sex (male or female), age (in 10-year age bands), marital status (single/ separated/divorced/widowed or married/in a domestic partnership), employment (yes or no) and annual household income (ie, <£15 000, £15 000-<£25 000, £25 000-<£40 000, £40 000-<£60 000, ≥£60 000). Participants were also asked to indicate which of the four main UK countries they lived in. Behavioural factors included current smoking status (yes or no), current alcohol consumption (yes or no) and usual levels of moderate-to-vigorous physical activity per day during non-pandemic times (when not selfisolating). Participants were also asked to report chronic physical conditions. Finally, participants were asked if they had experienced any physical symptoms of COVID-19 during social distancing and the number of days they had been social distancing.
Finally, when comparing the present sample with recent UK population estimates, women (64. 0% vs 50. 6%) and adults aged 18-34 years (31. 3% vs 19. 7% (20-34 years in the comparison database, strictly speaking)) are over-represented. 16 Moreover, it is indeed known that online surveys may not yield generalisable, epidemiological samples, but given the nature of restrictions in place on personal contacts there are few options to collect this type of data. The present findings suggest that during COVID-19, social distancing interventions should focus on increasing physical activity levels among younger adults, men and those with low annual household income. It should be noted in the present sample that women and younger adults are over-represented.
Screening and recruitment The questionnaire was administered through the free online software LimeSurvey. Twenty-four GPs pre-tested the online questionnaire in order to check its comprehensibility and acceptability. The survey period occurred between 14 March and 21 March 2020. One reminder was sent before the end of the survey period. The target population was GPs currently practising in France (n=46 056 in statutory health insurance database 2019). 7 Considering the surveyed population and an ideal random sampling strategy, the minimum sample size was 2283 GPs with a margin of error of 2% at a 95% confidence level. Practitioners were recruited by email using the contact lists of the different French scientific societies of GPs, which represent approximately 25 000 GPs, that is, 54. 3% of the study population.
Acknowledgements The authors are indebted to  Véronique Orcel  for her helpful review of the manuscript and to  Accord network (Assembler, Coordonner, COmprendre , Rechercher, Débattre en soins primaires) for their reflection and help in the construction of the questionnaire. ACCORD is composed of the  National College of GP Instructors (CNGE) ,  French Society of General Practice (SFMG) ,  National Federation of Multiprofessional Health Houses (AVECSanté) ,  Research Institute of Health Care Centres (IJFR) ,  URE RETINES (Risque, Epidémiologie, Territoire ,  INformations ,  Education en santé) Université de Nice, National Association of Health Teams in Primary Care (ASALEE), Mission RESPIRE (EHESP)  and the  Midwifery Department ,  EA 7285 ,  Versailles Saint Quentin University group.
Funding The study was funded by the non-govermental organization leading the VIF program FLVS (Fédérons Les Villes pour la Santé), gathering financial support from local authorities in addition to the contributions of private partners, including Nestlé Foundation, Ferrero France, BEL, and Roquette Foundation. The funding bodies had no input in the study design; data collection, analysis, and interpretation; writing of the report; or the decision to submit the report for publication.
Ethics approval and consent to participate The study protocol was approved by the CNIL (Commission Nationale Informatique et Libertés), a governmental body in charge of checking compliance with ethical and individual data protection regulations in France. The CNIL fulfills the role of the Institutional Review Board (IRB) in France for non-invasive research. Children's weight status and other variables were available from school medical service records and analysed after anonymization without Institutional Review Board oversight, as legally permitted in France (Article L. 541-1 du code de l'éducation) and in the United States (https://www. hhs. gov/ohrp/regulations-and-policy/decision-charts/index. html). The study's protocol was approved by local authorities in charge of children's education and care (municipal authorities, school directors, and school health services).
Research in the low-frequency range began more than 40 years ago, and there is now a large body of literature available on which ICNIRP set its protection guidelines. A review of the literature has been carried out to identify possible relevant knowledge gaps, and the aim of this statement is to describe data gaps in research that would, if addressed, assist ICNIRP in further developing guidelines and setting revised recommendations on limiting exposure to electric and magnetic fields. It is articulated in two parts: the main document, which reviews the science related to LF data gaps, and the annex, which explains the methodology used to identify the data gaps.
Moreover, since few sources commonly found in society use frequencies of between 100 Hz and 100 kHz, fewer studies of these frequencies have been conducted. There are scientifically substantiated acute effects on the functioning of the nervous system which can occur at high ELF MF levels as well as perception and annoyance relating to exposure to ELF-EFs. Exposure guidelines published by the International Commission on Non-Ionizing Radiation Protection (ICNIRP 2010) have been set to protect against such effects. Some epidemiological data suggest a possible association between exposure to ELF-MFs below guideline levels and health effects, although they are inconclusive. The International Agency for Research on Cancer (IARC) has classified ELF-MFs as a "possible carcinogen"  (IARC class 2B; IARC 2002).
Purpose The aim of this document is to identify data gaps in research that would, if addressed, assist ICNIRP in further developing guidelines and setting revised recommendations on limiting exposure to electric and magnetic fields. An algorithm was elaborated to identify the research needs; the details and the structure are described in the Appendix. The evaluation of certain research areas identified either a lack of knowledge in the literature or of inconclusive data where further research would be needed to improve knowledge about the biological effects of exposure from which guideline restrictions can be derived. Other areas provided sufficient information and were not considered to be in need of further research. Therefore, the topics that were considered not to be relevant are only briefly summarized, while the effects with potential relevance for setting guidelines are reported in specific sections.
Summary of research areas where further research is not considered necessary for guideline development The ICNIRP 2010 guidelines indicated that effects of ELF-MFs on neurobehavior could be explained by scientifically substantiated mechanisms of induction of retinal phosphenes and nerve-stimulation. Other effects were not consistently shown. Since then, a limited number of methodologically heterogeneous studies have investigated brain electrical activity, cognition, sleep, and mood in volunteers and human populations. With the exception of nerve stimulation due to contact currents (see below), research with volunteers continues to indicate no substantiated neurobehavioral effects below the existing guideline values, nor does it point to any significant data gaps that require further research.
There has been a lack of animal or mechanistic studies looking into this area since 2010. Overall, the evidence gathered so far does not indicate any data gaps that require research for guideline development. Also for cardiovascular disorders the research available at the time the ICNIRP 2010 Guidelines were drafted provided convincing null findings, which suggest there are no data gaps in this area that require research. Finally, looking at the knowledge on various health effects from co-exposure with ELF-MF, a meta-analysis concluded that the majority of the studies reviewed were positive, suggesting that ELF-MFs did interact with other chemical and physical exposures  (Juutilainen et al. 2006). On the other hand, the review by SCENIHR (2015) concluded that more recent experimental studies indicated that findings from co-exposures to physical or chemical agents with ELF-MFs lacked consistency.
One study used an animal model (WKAH/Hkm male rats) for chemically-induced B-ALL  (Bernard et al. 2008). In this study, exposure to a 50 Hz MF at 100 mT (with or without harmonics at 150, 250 or 350 Hz) did not significantly alter the incidence or the type of leukemia induced by the chemical. Within the EU Seventh Framework Program ARIMMORA project, a transgenic mouse model expressing the human ETV6-RUNX1 (formerly TEL-AML1) fusion gene was engineered to develop B-ALL. This model, when fully characterized, will be valuable for further investigations of a potential effect of ELF-MFs on childhood leukemia. Moreover, data on other pathological processes identified in B-ALL are also missing, such as epigenetic changes and angiogenesis, especially in the bone marrow. More recently, three studies were performed on rats exposed during gestation (12 th day of pregnancy) to natural death, to 50 Hz MFs from 2 to 1,000 mT either alone  (Bua et al.
Thus, additional data had suggested the possibility of effects below the basic restrictions recommended in the ICNIRP guidelines (100 mV m -1 ). This appeared to be a fruitful area for closing a data gap, but little has been done to follow up [some references in addition to those in  (WHO 2007)  were considered in (Wood 2008), but these did not provide a definitive resolution]. The phenomenon of magnetophosphenes, which are thought to arise from magnetic induction of electric fields in the neural networks of the retina, continues to be studied experimentally  (Legros et al. 2012; Souques et al. 2014)  and theoretically  (Laakso and Hirata 2012a and b). However, the precise locus, frequency dependence, and mechanism of the generation of this phenomenon are still unclear.
From that review, a model based on the classical excitable membrane physiology was suggested as one of the best candidates from available data (Wood 2008). There is also uncertainty regarding the derivation of reference levels of external magnetic field strength from the basic restrictions in the ICNIRP 21010 guidelines (ICNIRP 2010). Kavet  (Kavet 2015)  has estimated an "implicit" conversion factor (or coupling coefficient) for internal electric field in the peripheral nervous system (PNS) and has suggested that the reference level values are overly conservative in the ICNIRP 2010 guidelines. It was found that at the general public reference level, the "Head and Body" exposure is far less than the basic restriction by a factor of 2. 5 or more. The disparity exists across the frequency range and is due, in most part, to the different body models used.
g. ,  Kos et al. 2011; Laakso and Hirata 2012a and b) , and it is recommended that further research be conducted to clarify this issue. The relationship between internal electric fields and contact currents also requires further clarification. The poor understanding of this indirect coupling phenomenon is one reason that no basic restriction has been developed for the contact current stimulation effect. That is, since stimulation effects are assumed to be related to internal electric field, and there are only data relating the contact current (and not internal electric field) to health effects, it is not possible to determine the relation between health effects and the internal exposure itself. The issue of non-uniform distribution of current over the area of contact (which was not addressed in the ICNIRP 2010 guidelines) also needs clarification through additional experimental data.
The method of evaluation for non-sinusoidal waves, including pulses, is also an important topic worth investigating. In the low frequency guidelines, the Fourier transform analysis has been introduced based on the assumption that the interaction between internal fields and the nervous system can be represented with a simplified model. The relative conservativeness and appropriateness of this approximation have not been determined, and data gaps remain that could usefully be addressed in order to assist future development of guidelines. It is also noted that the evaluation method for nonsinusoidal waves is applicable up to 100 kHz in the ICNIRP 2010 guidelines, while the restrictions are set up to 10 MHz in the same guidelines. Because the evaluation method is based on the Fourier transform analysis or pure mathematics, the evaluation method can be expanded to frequencies higher than 100 kHz.