dataesr/scientific-paragraphs-categorization huggingface dataset:
Spatial distribution of infection groups. To gain further insight into the spatial distribution of infection patterns within Sénart Forest, we mapped the different IGs to which ticks belonged based on tick sampling locations (Supplementary Fig. S4 ). Further statistical analysis showed that most of the IGs were homogeneously distributed across the forest (data not shown). Host contributions to tick infection. One of our aims was to estimate the relative contributions of chipmunks, bank voles, and non-sampled hosts to the numbers of ticks infected by B. burgdorferi s. l. genotypes. We began by identifying SGGs in a dataset from which the two B. miyamotoi rplB GGs, G16 and G17, were excluded. GGs for both genes did not randomly infect ticks and hosts because 10 SGGs were found when co-occurrence patterns were analyzed (Fig.
burgdorferi species complex and relapsing-fever spirochetes (in red and gray). All genotypes with the same prefix (e. g. , G6) were empirically assigned to the same genotype group (GG) because of their close relationships. GGs that included strains isolated from humans are framed by a gray square. G11, G12, and G13 did not cluster with any other GGs identified in the dataset. To estimate the relative host contributions to tick infection, we compared our simulated data to the observed frequencies of these 10 SGG combinations. We determined the mean values of parameters of interest from posterior distributions (Supplementary Fig. S5 ). The estimates of the contribution parameters were α = 51. 0% (chipmunks), β = 3. 7% (bank voles), and γ = 45. 3% (non-sampled hosts).
This pattern may be explained by several non-exclusive hypotheses. It might be that some genotypes are limited in their ability to infect hosts but are able to circulate among ticks due to co-feeding  30. However, it is more likely that most of the genotypes identified in ticks are only maintained in host species that we did not sample. Our examination of sets of genotype groups (SGGs) and infection groups (IGs), along with our comparison of the genotypes we characterized with sequences from public databases, allowed us to propose candidate hosts. For instance, birds are likely involved in the circulation of some of the observed genotypes because one SGG included B. garinii and B. valaisiana genotypes (i. e. , GG5, GG8, and GG7), which would explain why the associated IG included only ticks.
17  , raw sequences were assigned to their respective nymphs or individual hosts and target loci using a BLASTN approach  43. The tag and the target sequence for each raw read were compared, respectively, to a list of the oligonucleotides used to tag the sequences obtained from each sample and a list of the different representative sequences of the target loci extracted from the B. burgdorferi MLST database (http://borrelia. mlst. net)  12 and GenBank  44. We only used the first 500 bp of the sequences in subsequent analyses, and sequences shorter than 350 bp were removed from the dataset. For each individual, we aligned the remaining sequences for each locus using K-Align  45. Genotype delineation and phylogeny. The main disadvantage of high-throughput sequencing methods, as compared to Sanger sequencing, is the high base-calling error rate.
It was based on raw sequence sampling at the whole-dataset scale with comparable sequencing efforts for ticks and hosts (same mean number of sequences per individual in both ticks and hosts). Here, we intended to compare the total number of genotypes found in ticks, in hosts, and in both ticks and hosts. For each of the 1000 sequence re-sampling of both genes, we computed the average number of delineated genotypes within individuals and the variance of the number of genotypes observed among individuals. We then used a phylogenetic approach to examine genotype diversity in greater detail. For each locus, consensus sequences and reference sequences were aligned with each other using K-Align  45. Phylogenetic searches were performed employing a maximum-likelihood approach and using PHYML  46.
Acknowledgements We thank the staff of the GATC, especially  Zelie Dubreucq  and  Marie-Elise Galoppini , for carrying out sequencing. This work was funded by the  French National Institute for Agricultural Research (INRA)  via the " AIP Bioressources 2011" program  and via the  OSCAR  project funded by the  French National Research Agency  ( Agrobiosphere program ). Maude Jacquot has received a PhD fellowship from the  French Ministry of Higher Education and Research (MESR). Interactions between scientists at  INRA  and the  Pasteur Institute  were funded by the  Tick and Tick-Borne Diseases (TMT) group , which is part of the  Research Consortium on Biological Interactions (GdR REID). Field sampling was conducted with the financial support of the regional government of  Ile-de-France  ( Conseil Regional d'Ile-de-France)  and the  French National Forests Office (Office National des Forêts).
Each data point is an average of 10 measurements at random positions on the wafer. This procedure leads to slightly inexact absolute thickness values, but it allows the determination of the thickness and sufficient precision for the comparison of the buildup and homogeneity of the different films. The variation of apparent refractive index for anisotropic samples as a function of aCNF orientation was measured using the SENpro spectroscopic ellipsometer. Therefore, anisotropic samples were rotated by 10°steps in the plane parallel to the substrate surface prior to measurements, and the ellipsometric angles psi (Ψ) and delta (Δ) were fitted at a fixed film thickness of 245 nm with isotropic refractive indices. Atomic Force Microscopy. Tapping mode atomic force microscopy was performed on an AFM Multimode from Bruker Nano Surface (Palaiseau, France) with a Nanoscope IV controller from Veeco (Mannheim, Germany) and noncoated silicon cantilevers (resonance frequency 300 kHz, resonance constant of 40 N/m, and radius below 10 nm).
Phase and height modes were recorded simultaneously using a constant scan rate of 1. 3 Hz with a resolution of 512 × 512 pixels. Orientation of aCNF. The orientation analysis of AFM images was carried out using the ImageJ software. The fast Fourier transform function of ImageJ was used to convert AFM images from "real" space into mathematically defined frequency space. Resulting FFT output images contain gray-scale pixels that are distributed in a pattern that reflects the degree of alignment present in the original data image. A round FFT pattern indicates no orientation in the original AFM image, while an elongated FFT pattern is characteristic of aCNF orientation in a given direction of the AFM image. In addition, OrientationJ, a plugin developed for ImageJ, was used to determine the distribution of orientation of aCNF with respect to the spraying direction.
ACKNOWLEDGMENTS We gratefully acknowledge financial support from the  European Community  ( SustainComp  project,  FP7-NMP-214660 ) and the  Centre National de la Recherche Scientifique (CNRS) ,  France. All  authors thank  Dr. Martin Brinkmann  ( ICS, France ) for providing access to the optical microscope,  Christophe Contal  ( ICS, France ) for the AFM training and imaging, and  Dr. Oriol Arteaga  ( University of Barcelona, Spain ) for fruitful discussions. M. P. thanks the " Chaire d'Excellence" program  of  CNRS  and the  Universitéde Strasbourg  for partial funding. G. D. thanks the  Institut Universitaire de France  for financial support.
Acknowledgements The authors thank  Dr. Giovanna De Luca  for enlightening discussions on the RLS results. This work was financially supported by the  EC  through the  European Research Council  project  SUPRAFUNCTION  ( GA-257305 ), the  Marie Sklodowska-Curie ITN  projects  SYNCHRONICS  ( GA 643238 ) and iSwitch (GA No. 642196 ), the  FP7-NMP-2012-SMALL-6 "SACS" project  ( GA-310651 ), the  Agence Nationale de la Recherche  through the  LabEx  project  Chemistry of Complex Systems  ( ANR-10-LABX-0026_CSC ), and the  International Center for Frontier Research in Chemistry (icFRC). Received: ((will be filled in by the editorial staff)) Revised: ((will be filled in by the editorial staff)) Published online: ((will be filled in by the editorial staff)).
Background: The data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases. Methods: Electronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). The pooled prevalence of clinical manifestations at presentation, ANCA and induction therapies for GPA and MPA was calculated.
Literature search We performed a systematic literature review and a metaanalysis, to obtain a best estimate of the prevalence of clinical manifestations at presentation and to review the treatments given to patients with childhood-onset GPA and MPA. The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed  [13]. We conducted a literature search on Medline and the Cochrane Central Register of Controlled trials database from January 1, 1950 to December 31, 2015, as reported on Additional file 1. We also checked the reference lists of the studies included and other systematic reviews on the topic, to identify additional reports.
Inclusion criteria and procedure We included all cohorts, cross-sectional studies or registries reporting data for features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). All papers providing a baseline description of the study population were considered. Studies reporting only data for specific subgroups of patients (e. g. only patients with nephritis) were excluded. The titles and abstracts of all the references identified were reviewed independently by two of the authors (MI, XP). The full text of the articles considered potentially relevant was then screened and checked for eligibility. Any disagreements about article inclusion were resolved at this stage.
Characteristics of the studies included We analysed data from 13 retrospective studies  [5-7, 9-12, 17-22]  and one prospective cohort  [23]. One study included two 20-year-old patients  [17]  and another used an upper limit of 19 years for the definition of childhood-onset AAV  [23] , but we decided to retain these studies in the analysis to prevent the loss of useful information. In total, data for 294 patients (69 % girls) were included. The main characteristics of studies included are summarised in Table  1.
We can, therefore, distinguish between NIHR Journals Library www. journalslibrary. nihr. ac. uk assessing the reliability of data and explaining the underlying phenomenon. 16 This may be considered a viewpoint from a realist philosophy of science. For example, in the evaluation of a patient safety initiative, Benning et al. 17, 18  measured errors and adverse events in multiple institutions. Multiple expert reviewers were used in the case note review, and there were controls for seasonal effects as well as reviewer learning and fatigue. However, these very real issues of data quality should not be conflicted with the phenomena to which they relate: in this case the link between intervention components and intervening variables and the link between intervening variables, clinical processes and adverse events (see Figure 1.
30 vances are being made in improving the efficiency with which literature reviews are conducted. For example, Tsafnat et al. 31  describe automated systematic review procedures and examine the impact such an automated process may have on each of the stages of the systematic review. However, much of this technology focuses on the review of RCTs, which are generally reported more consistently than observational studies which are likely to constitute much of the evidence for policy and generic service interventions. Indeed, many rapid-review methodologies still require the searching of multiple databases and manual review of retrieved abstracts. 32, 33 ce relevant studies have been identified, the next step is to assess them for quality. Quality assessment criteria have been widely established for both RCTs and observational studies.
58 milarly in the UK, cRCTs have been implemented using electronic health records to evaluate the effectiveness of computer-delivered decision support tools in reducing antibiotic prescribing for respiratory tract infections in primary care  59  and improving risk factor control after first stroke. 60 Both studies made use of electronic health records available via the Clinical Practice Research Datalink (CPRD), which includes anonymised data for approximately 7-8% of UK general practices, linked to a range of other data NIHR Journals Library www. journalslibrary. nihr. ac. uk including mortality information and cancer registrations. 61 This experience provides compelling evidence that RCTs may be performed efficiently in large samples of this kind. Process evaluation may also be carried out alongside this type of study.
62 wever, there are significant challenges. Those who contribute information to data sets such as CPRD are skilled at collecting data, and not necessarily representative of their peers. The geographical dispersal of sites in RCTs using electronic health records may present a challenge for research governance and intervention implementation. 63 For example, in a cRCT which used electronic records to study antibiotic prescribing, because the practices contributing to the CPRD are anonymous, permission had to be sought from 155 separate commissioning organisations for the English general practices alone. Further permissions were required in Scotland, Wales and Northern Ireland. The process took almost a year to complete before the RCT could commence. 63 Such requirements make it difficult to realise the potential efficiency gains of such trials.
Using observational data to improve external validity of randomised controlled trials There have been recent developments in using observational approaches and data to address the issue of external validity. These involve comparing the characteristics of RCT study samples with data from the population of people using (or eligible for) the intervention. Trial samples can be reweighted in line with the characteristics of people in routine practice, and then the outcomes of the people in the trial can be compared with those of people in routine practice. Placebo tests can then be used to assess the evidence for similarity of outcomes. Recent work by Hartman et al. 2  has built on previous approaches which have considered the external validity and generalisability of results from RCTs. The work illustrates how to extrapolate from the sample average treatment effect estimated from a RCT to a population average treatment effect for the population of interest, by combining results from experimental studies with observational studies.
Of these, 1293 individuals were matched with the RCT controls on 65 identified baseline covariates (e. g. demographics, blood pressure, medications). The placebo test then contrasted outcomes from the RCT between the matched target control population and the control group of the WSD trial. This process is described in greater detail in Steventon et al. 4  A comparison of the RCT control arm versus the matched controls from the observational data gave an incidence rate ratio of 1. 22 (95% CI 1. 05 to 1. 43) for emergency admissions. In other words, emergency admissions were significantly higher in the control arm of the WSD trial than in a similar group of patients who did not participate in the trial. Consequently, the trial results may have shown an inflated beneficial effect of telehealth interventions.
This reduces, or in the case of very large samples eliminates, the selection bias. The use of IVs will be illustrated with an example. A 2009 survey of service care utilisation by the elderly was carried out, with the aim of assessing the cost-effectiveness of the services provided. 12 In this case, the intensity of service utilisation was expected to be directly related to a patient's level of frailty and ill-health, as these factors are key elements in the patient's assessment of need. Therefore, methods had to be considered which distinguished the variation in care-related quality of life owing to service use as opposed to other factors. Data were collected on a range of outcome measures, including a measure of social care-related quality of life (SCRQOL), using the ASCOT measure. 13 As is common with health and care utilisation data, the observed relationship between the intensity of service utilisation and the outcome (care-related quality of life) was negatively sloped.
A case study: patient-reported outcome measures and NHS elective surgery Since 2009, the providers of care for NHS patients have been required to collect data before and 3 or 6 months after surgery with a condition-specific and a generic PROM for four elective procedures: hip replacements, knee replacements, groin hernia repair and varicose veins surgery. Importantly, the information generated is publicly available (www. hscic. gov. uk/proms) and guidance is provided to help the public navigate and interpret data for individual hospital trusts. The database has provided a uniquely rich source for evaluative research using the PROM. Some overall patterns are striking; for example, the evidence for the effectiveness of joint replacement (especially in terms of condition-specific measures) and the relative lack of evidence of provider trusts being consistently poor outlier performers in relation to appropriately adjusted PROMs are reassuring for the NHS.
Such data may distinguish the advantaged from the disadvantaged within an area and provide greater resolution on SEC when used in combination with the IMD. 14 The method is not bias free, however, as relatively high levels of consumerism may be the result of high debt, not affluence. Health and health-care researchers are perhaps less familiar with using sources such as local and national taxation information and education data, but forging links with data providers to explore such sources has the potential to reap benefits for future equity research. NIHR Journals Library www. journalslibrary. nihr. ac. uk Some relationships between health and measures of SEC are best characterised by J-shaped curves, meaning that the most disadvantaged group may not be where you expect to find them. For example, in the USA, health insurance coverage may not be linear with income; the wealthy may opt not to have health insurance, and benefit recipients may have state-provided coverage.
Where the clinical rationale for intervention is not clear-cut, investigation and treatment may be influenced as much by the availability of doctors and diagnostic equipment, or by financial factors (such as a fee-for-service system), as by clinical need. 17 This highlights the problem of inequity owing to the overuse of medical interventions, which puts patients at risk of complications unnecessarily and drives up the cost of health care. Finally, health-care systems which are not universal are limited by their access to medical record databases which relate only to the insured population, excluding those without coverage, and there may be also unknown missing data bias for out-of-area medical visits.
Sociodemographic variations in the likelihood of referral by GPs into secondary care has also been found to vary depending on the presence of explicit national guidelines on referral. 35 This study used The Health Improvement Network, a widely used primary care database, to examine sociodemographic variations in referral for potentially life-threatening conditions where national guidance on referral has been published [post-menopausal bleeding (PMB) and dyspepsia in people > 55 years of age] and for symptoms where there is clinical uncertainty regarding the decision to refer (hip pain and dyspepsia in people < 55 years of age). For the three conditions examined, older patients were less likely to be referred, after adjusting for comorbidity. Women were less likely than men to be referred for hip pain [hazard ratio (HR) 0.
12 However, there was consistent evidence of no sex difference in those patients in whom the results of previous investigations had been taken into account. This indicates that the sex inequalities identified were not inequitable, in that they were fair and made on the basis of clinical need (identified by the earlier investigation). Thus, the entire management pathway needs to be examined to establish the reasons for the differences found. The challenge is to identify data that will permit unbiased ascertainment of need and use across two or more settings (primary, secondary and community care). It is here that carefully specified individual record linkage between survey data to databanks of routinely collected data, and linking different sources of routinely collected data, is of high value.
44  the UK, Cookson et al. 45  evaluated these policies by examining trends in primary care access, quality and outcomes by SEC between 2004 and 2012. They did this using routinely available whole population data including health data from four national administrative databases. The IMD (IMD 2010)  46  was used to assign socioeconomic status to neighbourhoods of approximately 1500 people each. Slope indices of inequality were measured in four indicators: patients per family doctor, primary care quality, preventable hospitalisation and amenable mortality. They found that, during this period, the NHS succeeded in substantially reducing socioeconomic inequalities in primary care access and quality but made only modest reductions in health-care outcome inequalities. Such analyses cannot assess the extent to which observed trends in preventable hospitalisation and amenable mortality are attributable to, for example, trends in multimorbidity outside the control of the NHS or in social variations in illness behaviour.
chronic disease management project from the first round of the Greater Manchester Collaboration for Leadership in Applied Health Research and Care (CLAHRC), using Quality and Outcomes Framework information overlaid with a quality improvement intervention, Plan-Do-Study-Act methodology and facilitation, with data fed back on a monthly basis and benchmarked against other sites (http://clahrc-gm. nihr. ac. uk/our-work-2008-2013/chronic-kidney-disease/). NIHR Journals Library www. journalslibrary. nihr. ac. uk.
Acknowledgements The authors would like to thank the editors; co-authors of some of the paper cited in this essay, including  Noemi Kreif ,  Matt Sutton ,  Erin Hartmann  and  Adam Steventon ; and participants at the Evaluation London 2015 workshop. We would also like to thank  Jane Dennett  for her help in copy-editing and preparing this manuscript. Any errors and omissions are the responsibility of the authors.
zA chronic disease management project from the first round of the Greater Manchester Collaboration for Leadership in Applied Health Research and Care (CLAHRC), using Quality and Outcomes Framework information overlaid with a quality improvement intervention, Plan-Do-Study-Act methodology and facilitation, with data fed back on a monthly basis and benchmarked against other sites (http://clahrc-gm. nihr. ac. uk/our-work-2008-2013/chronic-kidney-disease/). NIHR Journals Library www. journalslibrary. nihr. ac. uk.