article: This study designed and applied accessible yet systematic methods to generate baseline information about the patterns and structure of Canada' s neglected tropical disease (NTD) research network; a network that, until recently, was formed and functioned on the periphery of strategic Canadian research funding. Multiple methods were used to conduct this study, including: (1) a systematic bibliometric procedure to capture archival NTD publications and co-authorship data; (2) a country-level “core-periphery” network analysis to measure and map the structure of Canada' s NTD co-authorship network including its size, density, cliques, and centralization; and (3) a statistical analysis to test the correlation between the position of countries in Canada' s NTD network (“k-core measure”) and the quantity and quality of research produced. Over the past sixty years (1950–2010), Canadian researchers have contributed to 1,079 NTD publications, specializing in Leishmania, African sleeping sickness, and leprosy. Of this work, 70% of all first authors and co-authors (n = 4,145) have been Canadian. Since the 1990s, however, a network of international co-authorship activity has been emerging, with representation of researchers from 62 different countries; largely researchers from OECD countries (e. g. United States and United Kingdom) and some non-OECD countries (e. g. Brazil and Iran). Canada has a core-periphery NTD international research structure, with a densely connected group of OECD countries and some African nations, such as Uganda and Kenya. Sitting predominantly on the periphery of this research network is a cluster of 16 non-OECD nations that fall within the lowest GDP percentile of the network. The publication specialties, composition, and position of NTD researchers within Canada' s NTD country network provide evidence that while Canadian researchers currently remain the overall gatekeepers of the NTD research they generate; there is opportunity to leverage existing research collaborations and help advance regions and NTD areas that are currently under-developed.
  The cadre of research and development focused on neglected tropical diseases is driven by a common mission: generating discoveries, treatments, and interventions that will help reduce the global burden of a significant group of communicable diseases that thrive in impoverished settings and affect over 1 billion of the world' s 2. 8 billion poorest people. Collaborative neglected tropical disease research and development (where researchers work together from across disciplines, institutions, sectors, and countries) is as a strategy increasingly used to mobilize technical resources and diffuse the liability and financial risks amongst researchers and institutions involved in developing and bringing innovative solutions to market. It' s also used to ensure research agendas are driven by the needs and priorities of low-and-middle income countries. While collaborative research networks have many attributes and characteristics, they can loosely be defined as formal or informal networks of individuals and organizations that are working together and share similar mandates, goals or activities [1], [2]. Formal research networks are typically established to meet specific organizational or policy goals (e. g. , building research capacity; encouraging connections between researchers and users; building multi-disciplinary research agendas) within specific fields. Globally, a surge of formal collaborative NTD research and development networks in the form of public private partnerships (PPPs) and product development partnerships (PDPs) have been emerging over the past ten years. The Drugs for Neglected Diseases Initiative (DNDi), the Institute for One World Health (iOWH); the Pediatric Dengue Vaccine Initiative (PDVI); the Human Hookworm Initiative (HHI); Rotavirus Accelerated Development and Introduction Plan; and Pneumococcal Vaccine Accelerated Development and Introduction Plan are initiatives that each involve formal commitments from a collective of organizations, from across sectors, working to generate and deliver NTD research and development solutions. Although promising for generating innovation and economic growth, collaborative research initiatives such as PPPs and PDP have also been criticized as serving private-industry interests and intended to boost industry public relations and access to human resources and financial gains from vulnerable markets [3], [4]. On the contrary, informal research networks are often characterized as dynamic and responsive collectives of researchers that tend to evolve on the periphery of formality and structure; often a result of researchers who partner with other researchers based on common and complimentary interests, expertise, and access to resources in a specific field [1], [5]. Literature related to informal NTD research networks has largely been published in the form of bibliometric co-authorship mapping studies and is increasingly emerging to inform critical dialogue and commentary about the role of publicly funded researchers and institutions in ensuring under-resourced regions have more equitable access to NTD innovations and delivery solutions [6], [7]. Informal research networks are important, as their adaptability and ‘grass-root attributes’ point to the nexus of innovation and the opportunity for research funding agencies to identify and target mechanisms (financial and non-financial) to best harness their performance and ensure the effective use of resources and research investments. Underlying the endorsement of collaborative research initiatives is the assumption that they will involve co-operative practices that result in strengthened productivity, quality, and relevance for all parties concerned. Although research that is conducted collaboratively has been identified as a means for multiple actors to access and produce new knowledge, gain peer recognition, and acquire professional opportunities and intrinsic awards [8], [9]; the extent to which neglected tropical disease research is driven by and takes advantage of the brain-power of low-and-middle income country experts and infrastructure is up for debate and a criticism of international and philanthropic collaborative research initiatives [10], [11]. Within Canada, while the area of NTDs has not been a strategic priority area for its research granting councils, in recent years there is indication of an emerging formal research network (through initiatives such as the Canadian Institute for Health Research (CIHR) Chair in Neglected Diseases and Grand Challenges Canada Rising Star winners) and an active informal Canadian NTD research community [12]. However, there exists a challenge and deficiency in generating evidence to understand the structure and demonstrate the equity, effectiveness, outcomes, and evolution of NTD research and development and research networks, domestically and on a global scale [13]–[15]. In an effort to generate evidence about Canada' s NTD publication activity and the structure of its research network, this study conducted a country-level co-authorship network analysis. Accessible yet systematic methods were designed and applied to generate a baseline for tracking and measuring patterns and trends in the production, specializations, composition, and position of researcher in Canada' s NTD research network. Archived co-authorship publication data were used, as a proxy for collaboration, to generate country-level network analysis measures (including components and size, density, cliques, and centralization). The data were further analyzed by examining the core-periphery structure of Canada' s NTD co-authorship network and testing the correlation between the participation of countries in collaborative publishing (groups) against the quantity and quality of publications. Understanding the structure of a network makes the grouping and position of its actor' s visible (individuals, institutions, or countries); and helps expose potential gaps within the network. Evidence increasingly suggests that the position of actors within a network influences and shapes the production, practice, and diffusion of research [16].
  In this study neglected tropical diseases are delineated as including diseases that cause significant morbidity and mortality in poor and rural populations but are the most severely neglected in terms of basic research, development, and deployment of safe and effective interventions [17]. The NTD list generated by Hotez et al (2006) was adopted for this study to focus the inclusion criteria and its NTD keyword classification. Hotez et al' s list is widely accepted as including the diseases with the most prevalent impact and includes the thirteen NTDs commonly known as roundworm, whipworm, hookworm, snail fever, elephantiasis, blinding trachoma, river blindness, Leishmania, Chagas disease, leprosy, African sleeping sickness, Guinea worm, and Buruli ulcer. Although there are slight nuances in how organizations and researchers define and categorize NTDs, they are commonly distinguished from the big three infectious diseases (HIV/AIDS, tuberculosis, and malaria), which generally receive significantly more research and development funding [12], [17]. A three-category classification was then developed for each NTD to ensure that a comprehensive search using appropriate terminology could be completed. Each NTD was classified by the common name (s); the scientific disease name (s); and the name of the disease agent. The World Health Organization (WHO) International Classification of Diseases [18] and the NIH-National Library of Medicine [19] informed the nomenclature development of the three-category classification and Scopus search string that was developed for the twelve NTDs (File S1). For the scope of this study, the scientific classification of the disease agent was limited to the genus and species. This classification was appropriate, given that the disease pathogen is invariant and must be a part of a research-driven solution. Archived co-authorship publication data are increasingly used to understand scientific production and research collaborations [20]–[23]. NTD publications that included Canadian first authors or co-authors (defined as at least one author whose institution is affiliated with a Canadian address) over a sixty year period (1950–2010) were gathered as raw data using the Scopus database. For the scope of this study co-authorship data was collected on authors one to nine. Scopus is a major multidisciplinary database for the social sciences, life sciences, health sciences, physical sciences, and arts and humanities and includes nearly 18,000 titles from more than 5,000 international publishers. In the field of tropical medicine, evidence suggests that Scopus includes 55% more papers on tropical medicine than the Thomson Reuters ISI Web of Knowledge database and has the largest selection of journals from more countries and with a greater variety of fields [24], [25]. It also allows a search of the addresses of all contributing authors. In order to run the search, the keyword taxonomy and search strategy for each of the thirteen NTDs was employed using the “TITLE-ABS-KEY” command, which searches all publication titles, abstracts, and keywords. To yield research authored or co-authored by researchers with a Canadian institutional affiliation, the AFFILCOUNTRY command was also used. Due to resource limitations, the scope of this study was limited to English-language scholarly work including peer-reviewed publications, publications in press, and peer-reviewed conference papers. Implications of these inclusion criterion are further described in the discussion section. An abstract inclusion-screening criteria was developed and tested by reviewers (n = 2) on a subset of publications. Duplicates were removed, the dataset of publications was screened, and publications were excluded from the study if they were: 1) not authored or co-authored by a researcher affiliated with a Canadian university or institution, 2) not focused on one of the thirteen identified neglected tropical diseases, or 3) non-scholarly publications (Table 1). The bibliometric data were standardized and coded by hand in order to correct misspellings and ensure consistency between author institutions and countries. A country codex was developed to categorize and analyze co-authors by country, world region continent, OECD status, and Gross Domestic Product (using the 2009 International Monetary Fund, World Economic Outlook Database). The co-authorship data generated through the Scopus bibliometric search strategy were formatted and run using UCINET and NetDraw software. The software UCINET is a network analysis tool that reads the matrices and performs statistical analysis of the whole network or measures of relationships within a network. The network metrics were calculated using the UCINET formulas, saved as both Excel and ##h files and exported to NetDraw for visual analysis. NetDraw is software that is compatible with UCINET and used to assemble, visualize, and analyze various network parameters [26]. The archival NTD publication data were used to create a binary relational matrix (also known as 1-mode data) that shows the presence of relationships between the country of each author within Canada' s NTD research network. Networks can be asymmetric (whereby links are directed one way) or symmetric (whereby links are undirected). Canada' s NTD research network represented a symmetric (undirected) network because each link between the contributing author country was reciprocated. In order to analyze the group relations and structural characteristics of Canada' s NTD research country network, a set of network-level measures, commonly used to support macro-level analysis, were calculated and applied (size, density, cliques, centrality degree, centralization, and k-core) (Table 2).
  Between 1950 and 2010, Canadian researchers contributed to the production of 1079 NTD publications as per the criterion established for this study. During this time 105 publications were produced from 1950–1980 and 974 were published from 1980–2010 (Figure 1). A majority of Canada' s NTD publications were authored solely by Canadians (n = 700). Patterns in Canada' s NTD country co-authorship activity are summarized in Table 3. Canada' s 1,079 NTD publications included a total of 4,145 first and co-authors, of which 2,888 were affiliated with a Canadian institution (70%). Researchers from Canadian institutions represented 82% (879/1,079) of all NTD publication first author affiliation and 65% (2,009/3,075) of co-authors. The 200 papers that Canadians did not first author were largely led by authors from North America and European OECD nations, including the United States, United Kingdom, France, and Germany (Figure 2). Authors from these countries also accounted for a majority of remaining co-authoring activity (17%). The non-OECD countries with the most authorship activity (first author and co-author) included Brazil (1. 5%), Iran (1. 5%), Peru (0. 7%), Uganda (0. 6%), and Vietnam (0. 6%). The vast difference in Canada' s publication activity between each NTD is depicted in Table 4. Based on publication count, researchers from Canadian institutions predominantly specialize in Leishmania disease research (n = 423), which represents 40% of all of Canada' s NTD publishing activity. The other NTDs most attended to by researchers from Canadian institutions include African sleeping sickness (n = 186), leprosy (n = 148), Chagas disease (n = 68), and roundworm (n = 51). Of Canada' s NTD publications, the diseases that appear to have the highest country collaboration rate include Chagas disease (57. 3%), elephantiasis (48. 4%), river blindness (47. 4%), blinding trachoma (45. 4%), and whipworm (45. 4%) (Table 4). Although it is the disease with the highest number of Canadian NTD publications, Leishmania ranked fifth in country collaboration (36. 8%). Country collaboration rate represents the percentage of Canada' s NTD publications with authors from one or more other country. It includes all first and co-authors. To avoid double count, it accounts for only one instance of each country affiliation per publication. For example, if two researchers from London School of Hygiene and Tropical Medicine are co-authors with three University of Toronto researchers on a publication it would count as one instance of country collaboration. In this study, the bibliometric data were run through UCINET to generate baseline structural measures of Canada' s NTD co-authorship research network over a sixty year period, 1950–2010. This time period was selected in order to generate a historic view of the structure of Canada' s entire NTD research network and to provide a starting point for identifying opportunities for subsequent analysis of sub-networks based on thematic patterns that emerge. The results identified a total of 62 countries within Canada' s NTD network, including 46 ‘cliques’ that have at least three country members; and 42 cliques with at least two country members. Canada' s entire NTD co-authorship network appears to have a moderately high density (42%) and centralized structure. Centralization is indicated by the high standard deviation (SD = 73. 97) of the centrality degree scores reported for each country (range = 1,541). Figure 3 represents a multi-dimensional visual scaling of Canada' s NTD research network and includes countries that have at least two country connections (n = 42). A total of sixteen countries only have a co-authorship connection with Canada and are not included in the map. These countries, which sit on the periphery of the network, are further discussed below. Analyzing the size and core-peripheriness of this network (measured through k-core measures) provides insight into patterns of affiliation between collaborating countries and helps illustrate who is connected to whom within the network. Core-peripheriness is the degree to which there is a group of nodes (actors) who are densely connected (the core) and a separate group of nodes who are loosely connected to the core and each other. A k-core represents the maximal group of actors, all of whom are connected to number (k) of other members of the group [16]. A 3k-core, for instance, is the set of countries or institutions linked to at least 3 other countries or institutions. As k increases, the remaining actors within the network map appear increasingly dense [16]. Applying the UCINET k-core procedure on Canada' s NTD co-authorship country network locates a clustering of collaborating countries in the middle right of the network map (Figure 3). The k-core measures indicate that Canada has a 7k-core NTD network where twelve countries (Canada, United States, United Kingdom, France, Germany, Switzerland, Uganda, Belgium, Kenya, Nigeria, Ghana, and Cameroon) all remain connected to each other as k increases from one to seven. K-core measures can identify the type of structure that characterizes a network (e. g. , centralized or core-periphery). In this country-level analysis, because the data collection was designed to always include ‘Canada’, the network would appear centralized. However, in SNA plotting, the k-core measures on a bar graph can help identify and validate the centralization of the network; by establishing whether the network has a ‘core-periphery’ structure. A core-periphery network structure indicates the variation in the number of actors in the network who are most connected to each other and those who are not. In a k-core bar graph, each bar represents the number of actors (nodes) that are dropped as each unit increases in k. By way of example, if Panama only has one country connection (with Canada), it would be represented in the first bar and dropped in the next. A k-core bar graph where all the bars are at the same height means that the same numbers of actors are removed at each increase in k. This indicates no core-periphery and little structure in the network. A k-core bar graph that steeply increases or decreases indicates structural variation (whereby the number of actors removed from the core changes abruptly). In general, the greater the percentage decrease in actors left in the core, the less a core-periphery [27]. Using this logic, the results of plotting Canada' s NTD k-core measures in a k-core bar graph are presented in Figure 4. Figure 4 illustrates that the pattern of Canada' s NTD research network k-core bar graph is not uniform across all of the bars, with increases and decreases as k increases. The percentage decrease of nodes left in the core is higher than approximately 80% of the other increments; which indicates dense connections among the subset of the twelve countries in the 7k-core countries and indicates a core-periphery structure. The countries that exist within the 7k-core network appear clustered between three main world regions: North America, Northern Europe, and Africa. Of the twelve countries within Canada' s 7k-core, there appears to be variation in the socio-economic status of the countries; there was a 7∶5 split in OECD and non-OECD country status core members (Table 5). All five non-OECD countries within the 7k-core are African nations, indicating a predominant grouping and connection of African nations working within Canada' s core-research group. Uganda and Kenya are the African nations with the most country connections (with other OECD and non-OECD countries) per publication, with both of their NTD research activities beginning in the mid-1990s and peaking between the years 2000 and 2005. Of the sixteen publications with Ugandan authors, a majority are focused on river blindness (n = 10). The others focused on African sleeping sickness (n = 4), hookworm (n = 1), and blinding trachoma (n = 1) and are classified within the fields of infectious disease (n = 7), biochemistry (n = 4), pediatrics (n = 3), and veterinary sciences. Nine of the publications with Ugandan researchers included researchers from Canada and one other country, and seven of the publications included researchers from at least four to six different countries (a majority including co-authors from the United States, Switzerland, and Germany and the others including a mix of neighboring African nations including Ghana, Kenya, Tanzania and others including Cameroon, Côte d' Ivoire, and Congo). The nine publications with Kenyan authors specialized in African sleeping sickness (n = 6). The other NTD areas of focus included Leishmania (n = 2) and riverworm (n = 1) in the fields of medicine (n = 2), pediatrics and child health (n = 2), biochemistry (n = 1), infectious disease (n = 1), immunology (n = 1), endocrinology (n = 1), and veterinary sciences (n = 1). A majority of the Kenyan publications (n = 6) included researchers from Canada and one other country, and three of them included Canada and three other countries (n = 1) or five other countries (n = 2). Relative to publications with Ugandan researchers, publications with Kenyan researchers had a greater co-authorship grouping with OECD nations including the United States, the United Kingdom, Switzerland, and Germany. Uganda and Nigeria were the only other African nations grouped with Kenya. The data suggest that within Canada' s entire NTD research network, the OECD countries within the 7k-core network are also the most active lead and contributing authors. Of the twelve countries that constitute the 7k-core, seven fall within the 80th percentile of Canada' s NTD research first-author count (Canada, United States, United Kingdom, France, Germany, Switzerland, and Kenya), two fell within the 50th and 70th first-author percentile (Belgium and Nigeria) and the remaining three fell within the 10th to 49th percentile (Uganda, Cameroon, and Ghana). A majority (85%) of the countries in the 7k-core are ranked within the top 25 countries with the greatest number of all contributing authors to Canada' s NTD research. Seven of the 7k-core countries fell within the 80th percentile, with the remaining countries placing over the 50th percentile. Of the five African nations within the 7k-core, a total of three (Ghana, Nigeria, and Kenya) had the lowest count of contributing authors. Canada, the United Kingdom, the United States, and France had the largest number of contributing authors in the 7k-core. These results suggest that contrary to the position and rank of 7k-core OECD nations, for most 7k-core African countries, just because they are well connected does not mean they demonstrate the most authorship activity. If a conventional bibliometric analysis based on authorship activity/country were the only technique used to understand co-authorship patterns, the analysis would have neglected countries that demonstrate multiple linkages and indication of greater group engagement relative to other countries. Ten of the twelve countries (83%) within the 7k-core ranked in the top 25 countries contributing to all of Canada' s NTD publications (n = 1079). Four fell into the 90th percentile (United States, United Kingdom, France, and Germany); two of the countries fell within the 80th percentile (Switzerland and Uganda) and the remaining fell within the 60th–70th percentile (Cameroon, Nigeria, and Ghana). The 7k-core countries were distributed across the ranking of the country SJR NTD publication average. Five of the countries fell within the 80–90th percentile rank for country NTD paper SJR average percentile (United States, United Kingdom, France, Germany, and Switzerland), four fell within the 60–70th percentile (Uganda, Kenya, Belgium, and Cameroon) and two countries fell within the 50th percentile (Nigeria and Ghana). These data point to a potential connection between a country' s connectivity (k-core), publication production, and quality rates, a correlation that is later examined. The countries that have < = 1 tie (and are dropped by UCINET in the k-core analysis) represent countries that exist on the periphery of Canada' s NTD co-authorship network. These countries (n = 16 of 62), which have only one co-authorship tie to Canada' s NTD publications (the one tie being to Canada), are outlined in Table 6 alongside the 2K-Core network. The 2K-core represents countries that have a maximum relationship with two countries (Canada plus one other country). In Canada' s NTD co-authorship country network, four countries fit within the 2K-core, including Costa Rica, Gambia, Cuba, and Syrian Republic. Combined, the 2K-Core and the countries with less than one tie represent countries from a range of regions including Latin America and the Caribbean (n = 7), Asia (n = 5), Africa (n = 4), and Eastern Europe (n = 3) and represent countries within Canada' s network within the lowest GDP percentile. Four countries in the 2K-core sit within the 75% lowest percentile of first author rank. Gambia is the anomaly, ranked in the middle of the first author pack but not heavily connected with Canada' s overall network. The network measures generated in this study help identify and characterize the groups of countries connected to Canada' s NTD network and provide important insights into the composition and structure of existing relationships. The findings prompt further question as to whether collaborative research amongst countries is associated with increased research productivity and quality. To test this hypothesis, the statistical analysis software Stata10 was used to run a Pearson' s correlation test on the 62 country observations (including Canada). The test was completed to identify the strength of relationship between each country' s k-core rank, SJR average, total count of NTD publications, and total first author count (File S2). The Pearson' s correlation test found an insignificant relationship amongst all of the variables. When the relationships were displayed in a scatter-graph it became evident that the design of the data collection resulted in the existence of an outlier, Canada. At minimum, all data had to include one Canadian author. The Pearson correlation is highly sensitive to outliers and therefore not an appropriate summary measure of the degree of relationship for this study. Rather than removing Canada from the test, a Spearman Rank Order Correlation coefficient (which is less sensitive to outliers) was run and found a strong positive correlation between the k-core and publication that was statistically significant (r = 0. 80, p<0. 01). A Bonferroni adjustment was then performed on the Spearman Rank Order Correlation to guard against cumulative type 1 error, and overall a positive relationship was also found among the variables (Spearman' s r = 0. 6937, p<0. 0083). The Bonferroni adjustment found a very strong relationship between a country' s k-core and total NTD publication count (Spearman' s r = 0. 8028, p<0. 0083), a moderately strong relationship between k-core and SJR average (Spearman' s r = 0. 6937, p<0. 008) and a positive but weak relationship between k-core and first authorship status (Spearman' s r = 0. 444, p<0. 0083). An analysis of the implications of these tests and results is included in the subsequent discussion section.
  The objective of this analysis is to understand Canada' s historic contribution to NTD publication activity and the core-periphery structure of Canada' s research network. It also discusses the features and characteristics of the international co-authoring partners and types of NTD research that is being conducted. In this study, the bibliometric information, country collaboration rates, and k-core measures used to analyze the authorship patterns and core-periphery of the network provide evidence that researchers in Canada currently remain the overall gatekeepers of the NTD research Canada generates. Gatekeepers represent individuals or institutions predominantly responsible for setting agendas [41]. Of Canada' s 1079 NTD publications, 64. 8% (n = 700) do not include international authors. This appears in spite of commitments such as the 2008 Bamako Call whereby Canada aims to ensure that partners from the South are leading the global health research agenda [42]. The methodology and findings from this study provides new insight to multiple stakeholders interested in evidence and trends in international research networks. Researchers, public and private funders, and not-for-profit organizations and policy makers may use the methodology or study findings to conduct focused case studies that measure, map, and assess the scientific activities of leading NTD researchers, institutions, and/or funding agents. All in all, this work substantiates the call for future analysis that looks at trends in specific NTD areas and the structures, actors, and factors that are supporting or impeding Canadians from partnering and publishing with LMIC researchers to further advance improvements in NTD research and development.
summary: This study applies co-authorship network analysis to generate baseline information about the patterns and structure of Canada' s neglected tropical disease (NTD) publication activity and research network. Researchers, public and private funders, not-for-profit organizations, and policy makers may use the methodology or study findings for targeting, monitoring, and assessing Canada' s contribution to a research field that is ready for attention and advancements. Future studies could use the findings to comparatively analyze the emergence of specific NTD research amongst institutional networks or further examine attributes and mechanisms that support and impede Canadian involvement in NTD research production and collaborative North–South research partnerships.
title: Canada's Neglected Tropical Disease Research Network: Who's in the Core—Who's on the Periphery?