Enhancing the scoping study methodology: a large, inter-professional team’s experience with Arksey and O’Malley’s framework

Background: Scoping studies are increasingly common for broadly searching the literature on a specific topic, yet researchers lack an agreed-upon definition of and framework for the methodology. In 2005, Arksey and O'Malley offered a methodological framework for conducting scoping studies. In their subsequent work, Levac et al. responded to Arksey and O'Malley's call for advances to their framework. Our paper builds on this collective work to further enhance the methodology. Discussion: This paper begins with a background on what constitutes a scoping study, followed by a discussion about four primary subjects: (1) the types of questions for which Arksey and O'Malley's framework is most appropriate, (2) a contribution to the discussion aimed at enhancing the six steps of Arskey and O'Malley's framework, (3) the strengths and challenges of our experience working with Arksey and O'Malley's framework as a large, inter-professional team, and (4) lessons learned. Our goal in this paper is to add to the discussion encouraged by Arksey and O'Malley to further enhance this methodology. Summary: Performing a scoping study using Arksey and O'Malley's framework was a valuable process for our research team even if how it was useful was unexpected. Based on our experience, we recommend researchers be aware of their expectations for how Arksey and O'Malley's framework might be useful in relation to their research question, and remain flexible to clarify concepts and to revise the research question as the team becomes familiar with the literature. Questions portraying comparisons such as between interventions, programs, or approaches seem to be the most suitable to scoping studies. We also suggest assessing the quality of studies and conducting a trial of the method before fully embarking on the charting process in order to ensure consistency. The benefits of engaging a large, inter-professional team such as ours throughout every stage of Arksey and O'Malley's framework far exceed the challenges and we recommend researchers consider the value of such a team. The strengths include breadth and depth of knowledge each team member brings to the study and time efficiencies. In our experience, the most significant challenges presented to our team were those related to consensus and resource limitations. Effective communication is key to the success of a large group. We propose that by clarifying the framework, the purposes of scoping studies are attainable and the definition is enriched

BiasBed -- Rigorous Texture Bias Evaluation

The well-documented presence of texture bias in modern convolutional neural networks has led to a plethora of algorithms that promote an emphasis on shape cues, often to support generalization to new domains. Yet, common datasets, benchmarks and general model selection strategies are missing, and there is no agreed, rigorous evaluation protocol. In this paper, we investigate difficulties and limitations when training networks with reduced texture bias. In particular, we also show that proper evaluation and meaningful comparisons between methods are not trivial. We introduce BiasBed, a testbed for texture- and style-biased training, including multiple datasets and a range of existing algorithms. It comes with an extensive evaluation protocol that includes rigorous hypothesis testing to gauge the significance of the results, despite the considerable training instability of some style bias methods. Our extensive experiments, shed new light on the need for careful, statistically founded evaluation protocols for style bias (and beyond). E.g., we find that some algorithms proposed in the literature do not significantly mitigate the impact of style bias at all. With the release of BiasBed, we hope to foster a common understanding of consistent and meaningful comparisons, and consequently faster progress towards learning methods free of texture bias. Code is available at https://github.com/D1noFuzi/BiasBe

Indications for pediatric hematopoietic stem cell transplantation: consensus presented at the First Meeting on Brazilian Hematopoietic Stem Cell Transplantation Guidelines - Brazilian Society of Bone Marrow Transplantation, Rio de Janeiro, 2009

The Brazilian Bone Marrow Transplant Society (SBTMO) held its First Meeting on Bone Marrow Transplant Guidelines in 2009. A working group of hematologists and oncologists with experience in pediatrics was formed to review evidence-based indications for pediatric transplants. Scientific publications were carefully assessed and, for each disease, the evidence for recommendation (from A to C) and the quality of the evidence (from 1 to 3) were defined. The recommendations include malignant and non-malignant hematological diseases, solid tumors, immunodeficiency, and storage diseases treated with hematopoietic stem cell transplants: either autologous or allogeneic from matched sibling donors or unrelated donors (adults or umbilical cord blood). Guidelines for reduced-intensity transplants, manipulated grafts or partially compatible donors were not included as there are no uniformly accepted recommendations. All indications are based on the best current knowledge which may change over time. Thus, this review should not be directly applied to patient care without taking into account the disease, donor and patient characteristics. Additionally, this paper should not be used as a document to limit patient access to transplant if correctly indicated. In this review we also point out differences between transplantation in adults and children and make some specific recommendations for pediatric transplants.A Sociedade Brasileira de Transplante de Medula (SBTMO) promoveu o I Encontro de Diretrizes do Transplante de Medula Óssea em 2009. Para revisão das indicações de transplante em Pediatria baseadas em evidências foi constituído grupo de trabalho com oncologistas e hematologistas com experiência em pediatria. Os artigos científicos foram cuidadosamente avaliados e, para cada doença, foram definidas as evidências para recomendação dos transplantes (de A a C) e a qualidade destas evidências (de 1 a 3). As recomendações incluem doenças hematológicas malignas e não malignas, tumores sólidos, imunodeficiências e doenças de depósito tratadas com transplantes de células-tronco hematopoéticas, quer autólogos, alogênicos de irmão HLA compatível ou não aparentados (doadores adultos ou sangue de cordão umbilical). Como não existem recomendações uniformemente aceitas em pediatria, não foram incluídas recomendações para transplantes de intensidade reduzida, com manipulação do enxerto e nem parcialmente compatíveis. É importante ressaltar que todas as indicações são baseadas no conhecimento atual e podem modificar-se com o tempo. Assim, esta revisão não deve ser utilizada para aplicação direta no cuidado do paciente sem levar em conta características da doença, do doador e fatores de risco do próprio paciente. Este trabalho não deve ainda ser utilizado como documento que limite o acesso do paciente ao transplante adequadamente indicado. Ressaltamos ainda, nesta revisão, diferenças entre transplantes em crianças e em adultos, com algumas recomendações específicas para os transplantes em pediatria.UNIFESPUniversidade Federal do ParanáUFRGSHospital Amaral CarvalhoHospital de Clínicas de Porto AlegreUNIFESPSciEL

Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia.

Although the graft-versus-leukemia effect of allogeneic bone marrow transplantation (BMT) is of paramount importance in the maintenance of disease remission, the role played by the autologous T-cell response in antitumor immune surveillance is less defined. We evaluated the emergence of antileukemia cytotoxic T-lymphocyte precursors (CTLp's) and the correlation of this phenomenon with maintenance of hematologic remission in 16 children with acute myeloid leukemia (AML), treated with either chemotherapy alone (5 patients) or with autologous BMT (A-BMT, 11 patients). Antileukemia CTLp's were detectable in 8 patients in remission after induction chemotherapy; none of them subsequently had a relapse. Of the 8 patients who did not show detectable CTLp frequency while in remission after induction chemotherapy, 7 subsequently experienced leukemia relapse. In patients undergoing A-BMT, molecular fingerprinting of the TCR-Vbeta repertoire, performed on antileukemia lines, demonstrated that selected antileukemia T-cell clonotypes, detectable in bone marrow before transplantation, survived ex vivo pharmacologic purging and were found in the recipient after A-BMT. These data provide evidence for an active role of autologous T cells in the maintenance of hematologic remission and also suggest that quantification of antileukemia CTLp frequency may be a useful tool to identify patients at high risk for relapse, thus potentially benefiting from an allogeneic antitumor effect

Investigation of oral and general health status and IL-1β gene polymorphism as risk factors for oral mucositis in hematopoietic stem cell transplantation patients

The aim of the present study was to analyze the relationship of OM with possible risk factors such as oral health condition, immunological status and IL-1β profile in patients submitted to hematopoietic stem cell transplantation (HSCT). Fifty-four individuals submitted to HSCT were included. All patients received previous dental treatment and photobiomodulation (PBM) as the institutional OM preventive protocol. OM scores, immune status, and IL-1β levels were determined during the conditioning period and at D+3 and D+8 after HSC infusion. IL-1β gene polymorphism was also analyzed during conditioning. Possible associations of OM with risk factors were analyzed using conditional Fisher’s exact test. OM was observed in 34 patients (62.9%) classified as Grade 1 (13 patients/24.1%), Grade 2 (14 patients/25.9%), Grade 3 (3 patients/5.5%), and Grade 4 (4 patients/7.4%). Allogeneic HSCT individuals exhibited a higher OM grade than autologous subjects. Moreover, an association was observed between severe OM and severe gingivitis (p = 0.01), neutropenia (p = 0.03), and leukopenia (p = 0.04). A significant association between OM and lower IL-1β levels was detected at three time points, i.e., conditioning (p = 0.048), D+3 (p = 0.01), and D+8 (p = 0.005). The results showed that IL-1β gene polymorphism was not associated with OM. Our study provided important insights into the scope of OM risk factors in the setting of HSCT. Patients submitted to HSCT with severe gingivitis prior to chemotherapy and with severe neutropenia and leukopenia exhibited a higher OM grade. Further investigation will be necessary to better understand the exact role of IL-1β in the context of OM pathobiology and to validate cytokine analysis in larger cohorts

Molecular identification of papillomavirus in ducks

Papillomaviruses infect many vertebrates, including birds. Persistent infections by some strains can cause malignant proliferation of cells (i.e. cancer), though more typically infections cause benign tumours, or may be completely subclinical. Sometimes extensive, persistent tumours are recorded– notably in chaffinches and humans. In 2016, a novel papillomavirus genotype was characterized from a duck faecal microbiome, in Bhopal, India; the sixth papillomavirus genotype from birds. Prompted by this finding, we screened 160 cloacal swabs and 968 faecal samples collected from 299 ducks sampled at Ottenby Bird Observatory, Sweden in 2015, using a newly designed real-time PCR. Twenty one samples (1.9%) from six individuals (2%) were positive. Eighteen sequences were identical to the published genotype, duck papillomavirus 1. One additional novel genotype was recovered from three samples. Both genotypes were recovered from a wild strain domestic mallard that was infected for more than 60 days with each genotype. All positive individuals were adult (P = 0.004). Significantly more positive samples were detected from swabs than faecal samples (P < 0.0001). Sample type data suggests transmission may be via direct contact, and only infrequently, via the oral-faecal route. Infection in only adult birds supports the hypothesis that this virus is sexually transmitted, though more work is required to verify this.Thanks to duck trappers at Ottenby Bird Observatory for support and sample collection, and to Abbtesaim Jawad for DNA extraction. This work was supported by the Crafoord Foundation Sweden (grants number 20160971 and 20170671). This is contribution no. 306 from Ottenby Bird Observatory